Title of Invention	NOVEL PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS
Abstract	The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease

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Field of Invention The present invention relates to novel hepatitis C virus ("HCV") protease inhibitors, pharmaceutical compositions containing one or more such inhibitors, methods of preparing such.inhibitors and methods of using such inhibitors to treat hepatitis C and related disorders. This invention specifically discloses novel peptide compounds as inhibitors of the HCV NS3/NS4a serine protease. Background of the Invention Hepatitis C virus (HCV) is a (+)-sense single-stranded RNA virus that has been implicated as the major causative agent in non-A, non-B hepatitis (NANBH), particularly in blood-associated NANBH (BB-NANBH)(see, International Patent Application Publication No. WO 89/04669 and European Patent Application Publication No. EP 381 216). NANBH is to be distinguished from other types of viral-induced liver disease, such as hepatitis A virus (HAV), hepatitis B virus (HBV), delta hepatitis virus (HDV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV), as well as from other forms of liver disease such as alcoholism and primary biliar cirrhosis. Recently, an HCV protease necessary for polypeptide processing and viral replication has been identified, cloned and expressed; (see, e.g., U.S. Patent No. 5,712,145). This approximately 3000 amino acid polyprotein contains, from the amino terminus to the carboxy terminus, a nucleocapsid protein (C), envelope proteins (E1 and E2) and several non-structural proteins (NS1, 2, 3,4a, 5a and 5b). NS3 is an approximately 68 kda protein, encoded by approximately 1893 nucleotides of the HCV genome, and has two distinct domains: (a) a serine protease domain consisting of approximately 200 of the N-terminal amino acids; and (b) an RNA-dependent ATPase domain at the C-terminus of the protein. The NS3 protease is considered a member of the chymotrypsin family because of similarities in protein sequence, overall three-dimensional structure and mechanism of catalysis. Other chymotrypsin-like enzymes are elastase, factor Xa, thrombin, trypsin, plasmin, urokinase, tPA and PSA. The HCV NS3 serine protease is responsible for proteolysis of the polypeptide (polyprotein) at the NS3/NS4a, NS4a/NS4b, NS4b/NS5a and NS5a/NS5b junctions and is thus responsible for generating four viral proteins during viral replication. This has made the HCV NS3 serine protease an attractive target for antiviral chemotherapy. It has been determined that the NS4a protein, an approximately 6 kda polypeptide, is a co-factor for the serine protease activity of NS3. Autocleavage of the NS3/NS4a junction by the NS3/NS4a serine protease occurs intramolecularly (he., cis) while the other cleavage sites are processed iritermolecularly (i.e., trans). Analysis of the natural cleavage sites for HCV protease revealed the presence of cysteine at P1 and serine at P1' and that these residues are strictly conserved in the NS4a/NS4b, NS4b/NS5a and NS5a/NS5b junctions. The NS3/NS4a junction contains a threonine at P1 and a serine at P1\ The Cys-»Thr substitution at NS3/NS4a is postulated to account for the requirement of cis rather than trans processing at this junction. See, e.g., Pizzi et al. (1994) Proc. Natl. Acad. Sci (USA) .£1:888-892, Failla etal. (1996) Folding & Design 1:35-42. The NS3/NS4a cleavage site is also more tolerant of mutagenesis than the other sites. See, ag^ Kollykhalov etal. (1994) J. Virol. 68:7525-7533. It has also been found that acidic residues in the region upstream of the cleavage site are required for efficient cleavage. See, e.g., Komoda etal. (1994) J. Virol. 68:7351-7357. Inhibitors of HCV protease that have been reported include antioxidants (see, International Patent Application Publication No. WO 98/14181), certain peptides and peptide analogs (see, International Patent Application Publication No. WO 98/17679, Landro etal. (1997) Biochem. 36:9340-9348, Ingallinella etal. (1998) Biochem. 37:8906-8914, Llinas-Brunet et al. (1998) Bioorg. Med. Chem. Lett. 8:1713-1718). inhibitors based on the 70-amino acid polypeptide eglin c (Martin etal. (1998) Biochem. 37:11459-11468, inhibitors affinity selected from human pancreatic secretory trypsin inhibitor (hPSTI-C3) and minibody repertoires (MBip) (Dimasi etal- (1997) J. Virol, 71:7461-7469). cVHE2 (a "cameiized" variable domain antibody fragment) (Martin et al.(1997) Protein Ena, 10:607-614). and cc1-antichymotrypsin (ACT) (Elzouki etal.) (1997) J. Hepat. 27:42-28). A ribozyme designed to selectively destroy hepatitis C virus RNA has recently been disclosed (see, BioWorld Today 9(217): 4 (November 10,1998)). Reference is also made to the PCT Publications, No. WO 98/17679, published April 30,1998 (Vertex Pharmaceuticals Incorporated); WO 98/22496, published May 28,1998 (F. Hoffmann-La Roche AG); and WO 99/07734, published February 18,1999 (Boehringer Ingelheim Canada Ltd.). HCV has been implicated in cirrhosis of the liver and in induction of hepatocellular carcinoma. The prognosis for patients suffering from HCV infection is currently poor. HCV infection is more difficult to treat than other forms of hepatitis due to the lack of immunity or remission associated with HCV infection. Current data indicates a less than 50% survival rate at four years post cirrhosis diagnosis. Patients diagnosed with localized resectable hepatocellular carcinoma have a five-year survival rate of 10-30%, whereas those with localized unresectable hepatocellular carcinoma have a five-year survival rate of less than 1%. Reference is made to A. Marchetti et a/, Synlett, Si. 1000-1002 (1999) describing the synthesis of bicylic analogs of an inhibitor of HCV NS3 protease. A compound disclosed therein has the formula: Reference is also made to W. Han et al, Bioorganic & Medicinal Chem. Lett, (2000) 10, 711-713, which describes the preparation of certain a-ketoamides, a-ketoesters and a-diketones containing allyl and ethyl functionalities. Reference is also made to WO 00/09558 (Assignee: Boehringer Ingelheim Limited; Published February 24, 2000) which discloses peptide derivatives of the formula: where the various elements are defined therein. An illustrative compound of that series is: Reference is also made to WO 00/09543 (Assignee: Boehringer ingelheim Limited; Published February 24, 2000) which discloses peptide derivatives of the formula: where the various elements are defined therein. An illustrative compound of that series is: Current therapies for hepatitis C include interferon-a (INFa) and i combination therapy with ribavirin and interferon. See, e.g., Beremguer etal. (1998) Proc, Assoc. Am. Physicians 110(21:98-112. These therapies suffer from a low sustained response rate and frequent side effects. See, e.g., Hoofnagle etal. (1997) N. Enal. J, Med. 336:347. Currently, no vaccine is available for HCV infection. Pending and copending U. S. patent applications, Serial No. 60/194,607, filed April 5, 2000, and Serial No. 60/198,204, filed April 19, 2000, Serial No. 60/220,110, filed July 21, 2000, Serial No. 60/220,109, filed July 21, 2000, Serial No. 60/220,107, filed July 21, 2000, Serial No. 60/254,869, filed December 12, 2000, and Serial No. 60/220,101, filed July 21, 2000, disclose various types of peptides and/or other compounds as NS-3 serine protease inhibitors of hepatitis C virus. There is a need for new treatments and therapies for HCV infection. It is, therefore, an object of this invention to provide compounds useful in the treatment or prevention or amelioration of one or more symptoms of hepatitis C. It is a further object herein to provide methods of treatment or prevention or amelioration of one or more symptoms of hepatitis C. A still further object of the present invention is to provide methods for modulating the activity of serine proteases, particularly the HCV NS3/NS4a serine protease, using the compounds provided herein. Another object herein is to provide methods of modulating the processing of the HCV polypeptide using the compounds provided herein. Summary of the invention In its many embodiments, the present invention provides a novel class of inhibitors of the HCV protease, pharmaceutical compositions containing one or more of the compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention or amelioration or one or more of the symptoms of hepatitis C. Also provided are methods of modulating the interaction of an HCV polypeptide with HCV protease. Among the compounds provided herein, compounds that inhibit HCV NS3/NS4a serine protease activity are preferred. The present application discloses a compound, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound having the general structure shown in Formula I: « * Formula I wherein: Y is selected from the group consisting of the following moieties: alkyl, alkyl-aryl, heteroalkyl, heteroaryl, aryl-heteroaryl, alkyl-heteroaryl, cycloalkyl, aikyloxy, alkyl-aryloxy, aryloxy, heteroaryloxy, heterocycloalkyloxy, cycloalkyloxy,, alkylamino, arylamino, alkyl-arylamino, arylamino, heteroarylamino, cycloalkylamino and heterocycloalkylamino, with the proviso that Y maybe optionally substituted with X11 or X12; X11 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, heterocyclyl, heterocyclylalkyl, aryl, alkylaryl, arylalkyl, heteroaryl, alkylheteroaryl, or 11 heteroarylalkyl, with the proviso that X may be additionally optionally substituted with X12; X12 is hydroxy, alkoxy, aryloxy, thio, alkylthio, arylthio, amino, alkylamino, arylamino, alkylsulfonyl, arylsulfonyl, alkylsulfonamido, arylsulfonamido, carboxy, carbalkoxy, carboxamido, alkoxycarbonylamino, alkoxycarbonyloxy, alkylureido, arylureido, halogen, cyano, or nitro, with the proviso that said alkyl, alkoxy, and aryl may be additionally optionally substituted with moieties independently selected from X12; R1 is COR5 or B(OR)2, wherein R5 is H, OH, OR8, NR9R10, CF3, C2F5, C3F7, CF2R6, R6, or COR7 wherein R7 is H, OH, OR8, CHR9R10, or NR9R10 , wherein R6, R8, R9 and R10 are independently selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, cycloalkyl, arylalkyl, heteroarylalkyl, [CH(R1')]pCOOR11, [CH(R1")] pCONR12R13, [CH(R1')]pS02R11, [CH(Rr)]pCOR11f [CH(Rr)]pCH(OH)R11, CH(R1' )CONHCH(R2' )COO R11, CH(Rr)CONHCH(R2')CONR12R13, CH(R1')CONHCH(R2' )R', CH(R1')CONHCH(R2')CONHCH(R3')COO R11, CH(R1)CONHCH(R2')CONHCH(R3)CONR12R13, CH(Rr)CONHCH(R2')CONHCH(R3')CONHCH(R4')COOR11( CH(R1')CONHCH(R2')CONHCH(R3')CONHCH(R?)CONR12R13, CH(R1')CONHCH(R2' )CONHCH(R3')CONHCH(R4')CONHCH(R5')COO R11 and CH(R1' )CONHCH(R2' )CONHCH(R3')CONHCH(R4')CONHCH(R5') CONR12R13, wherein R1', R2', R3', R4', R5', R11, R12, R13, and R' are independently selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, alkyl-aryl, alkyl-heteroaryl, aryl-alkyl and heteroaralkyl; Z is selected from O, N, CH or CR; W may be present or absent, and if W is present, W is selected from C=0, C=S, C(=N-CN), or S02; Q may be present or absent, and when Q is present, Q is CH, N, P, (CH2)P, (CHR)P , (CRR')p , O, NR, S, or S02; and when Q is absent, M may be present or absent; when Q and M are absent, A is directly linked to L; A is O, CH2, (CHR)P , (CHR-CHR')P , (CRR')P, NR, S, S02 or a bond; E is CH, N, CR, or a double bond towards A, L or G; G may be present or absent, and when G is present, G is (CH2)p, (CHR) p, or (CRR')P; and when G is absent, J is present and E is directly connected to the carbon atom in Formula I as G is linked to; J maybe present or absent and when J is present, J is (Chbjp, (CHR)P, or (CRR')P, S02, NH, NR or O; and when J is absent, G is present and E is directly linked to N shown in Formula I as linked to J; L may be present or absent, and when L is present, L is CH, CR, O, S or NR; and when L is absent, then M may be present or absent; and if M is present with L being absent, then M is directly and independently linked to E, and J is directly and independently linked to E; M may be present or absent, and when M is present, M is O, NR, S, S02, (CH2) p, (CHR)p (CHR-CHR%, or (CRR')P ; p is a number from 0 to 6; and R, R\ R2, R3 and R4 are independently selected from the group consisting of H; C1-C10 alkyi; C2-C10 alkenyl; C3-C8 cydoalkyl; C3-C8 heterocycloalkyl, -alkoxy, aryloxy, alkylthio, arylthio, amino, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, halogen; (cycloaikyl)alkyl and (heterocycloalkyl)alkyl, wherein said cydoalkyl is made of three to eight carbon atoms, and zero to six oxygen, nitrogen, sulfur, or phosphorus atoms, and said alkyl is of one to six carbon atoms; aryl; heteroaryl; alkyl-aryl; and alkyl-heteroaryl; wherein said alkyl, heteroalkyl, alkenyl, heteroalkenyl, aryl, heteroaryl, cydoalkyl and heterocycloalkyl moieties may be optionally and chemically-suitably substituted, with said term "substituted" referring to optional and chemically-suitable substitution with one or more moieties selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, aralkyl, cydoalkyl, heterocyclic, halogen, hydroxy, thio, alkoxy, aryloxy, alkylthio, arylthio, amino, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, sulfonamido, sulfoxide, sulfone, sulfonyl urea, hydrazide, and hydroxamate; further wherein said unit N-C-G-E-L-J-N represents a five-membered or six-membered cyclic ring structure with the proviso that when said unit N-C-G-E-L-J-N represents a five-membered cyclic ring structure, or when the bicyclic ring structure in Formula I comprising N, C, G, E, L, J, N, A, Q, and M represents a five-membered cyclic ring structure, then said five-membered cyclic ring structure lacks a carbonyl group as part of the cyclic ring. Among the above-stated definitions for the various moieties of Formula I, the preferred groups for the various moieties are as follows: Preferred definition for R1 is COR5 with R5 being H, OH, COOR8 or CONR9R10, where R8, R9 and R10 are defined above. Still preferred moiety for R1 is COCONR9R10, where R9 is H; and R10 is H, R14, [CH(Rr)]pCOOR11, [CH(R1')] pCONR12R13, [CH(R1')]pS02R11, [CH(R1')]pS02N R12R13, [CH(Rr)]pCOR11, CH(Rr)CONHCH(R2')COOR11, CH(R1')CONHCH(R2') CONR12R13, or CH(R1')CONHCH(R2')(R'), wherein R14 is H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, alkyl-aryl, alkyl-heteroaryl, aryl-alkyl, alkenyl, alkynyl or heteroaralkyl. Among the above for R , preferred moieties for R are: H, R14, CH(Rr)COOR11, CH(R1')CH(Rv)COOR11, CH(Rr)CONR12R13, CH(Rr)CH(Rr)CONR12R13, CH(Rr)CH(Rr)S02R11, CH(Rr)CH(R1')S02N R12R13f CH(Rr)CH(Rr)COR11, CH(Rr)CONHCH(R2')COOR11, CH(Rr)CONHCH(R2') CONR12R13, or CH(Rr)CONHCH(R2f)(R-)f wherein R1' is H or alkyl, and R2' is phenyl, substituted phenyl, hetero atom-substituted phenyl, thiophenyl, cycloalkyl, piperidyl or pyridyl. 1' 11 More preferred moieties are: for R is H, for R is H, methyl, ethyl, allyl, tert- butyl, benzyl, a-methylbenzyi, a,a-dimethylbenzyl, 1-methylcyclopropyl or 1- methylcyclopentyi; for R' is hydroxymethyl or CH2CONR12R13 where NR12R13 is selected from the group consisting of: wherein: U1 and U2 maybe same or different and are selected from H, Ft CH2COOH, CH2COOMe, CH2CONH2, CH2CONHMe, CH2CONMe2l azido, amino, hydroxyl, substituted amino, substituted hydroxyl; U3 and U4 maybe same or different and are selected from O and S; U5 is selected from the moieties consisting of alkyl sulfonyl, aryl sulfonyl, heteroalkyl sulfonyl, heteroaryl sulfonyl, alkyl carbonyl, aryl carbonyl, heteroalkyl carbonyl, heteroaryl carbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl or a combination thereof. i Preferred moieties for R2 are: As showrfin Formula I, the unit: represents a cyclic ring structure, which may be a five-membered or six-membered ring structure. When that cyclic ring represents a five-membered ring, it is a requirement of this invention that that five-membered cyclic ring does not contain a carbonyl group as part of the cyclic ring structure. Preferably, that five-membered ring is of the structure: wherein R and R' are defined above. Preferred representations for that five-membered cyclic ring structure is: where R20 is selected from the following moieties: Furthermore, that five-membered ring, along with its adjacent two exocyclic carbonyls, may be represented as follows: in which case, R21 and R22 may be the same or different and are independently selected from the following moieties: In c± G and J are independently selected from the group consisting of (CH2)P, (CHR)p, (CHR-CHR')p, and (CRR')P; A and M are independently selected from the group consisting of O, S, S02l NR, (CH2) P, (CHR)P, (CHR-CHR')P, and (CRR')P; and Q is CH2, CHR, CRR', NH, NR, O, S, S02, NR, (CH2)P, (CHR)P, and (CRR')P. Preferred definitions for c are: Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. Thus, for example, the term alkyl (including the alkyl portions of alkoxy) refers to a monovalent group derived from a straight or branched chain saturated hydrocarbon by the removal of a single atom having from 1 to 8 carbon atoms, preferably from 1 to 6; aryl - represents a carbocyclic group having from 6 to 14 carbon atoms and having at least one benzenoid ring, with all available substitutable aromatic carbon atoms of the carbocyclic group being intended as possible points of attachment Preferred aryl groups include phenyl, 1-naphthyl, 2-naphthyI and indanyl, and especially phenyl and substituted phenyl; aralkyl - represents a moiety containing an aryl group linked vial a lower alkyl; alkylaryl - represents a moiety containing a lower alkyl linked via an aryl group; cycloalkyl - represents a saturated carbocyclic ring having from 3 to 8 carbon atoms, preferably 5 or 6, optionally substituted. heterocyclic - represents, in addition to the heteroaryl groups defined below, saturated and unsaturated cyclic organic groups having at least one O, S and/or N atom interrupting a carbocyclic ring structure that consists of one ring or two fused rings, wherein each ring is 5-, 6- or 7-membered and may or may not have double bonds that lack delocalized pi electrons, which ring structure has from 2 to 8, preferably from 3 to 6 carbon atoms, e.g., 2- or 3-piperidinyI, 2- or 3-piperazinyl, 2- or 3-morpholinyl, or 2- or 3«thiomorpholinyl; halogen - represents fluorine, chlorine, bromine and iodine; heteroaryl - represents a cyclic organic group having at least one O, S and/or N atom interrupting a carbocyclic ring structure and having a sufficient number of delocalized pi electrons to provide aromatic character, with the aromatic heterocyclyl group having from 2 to 14, preferably 4 or 5 carbon atoms, e.g., 2-, 3- or 4-pyridyl, 2- or 3-furyl, 2- or 3-thienyl, 2-, 4- or 5-thiazolyl, 2- or 4-imidazolyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, or 3- or 4-pyridazinyl, etc. Preferred heteroaryl groups are 2-, 3- and 4-pyridyl; such heteroaryl groups may also be optionally substituted. Additionally, unless otherwise specifically defined, as stated above, the term "substituted or unsubstituted" or "optionally substituted" refers to the subject moiety being optionally and chemically-suitably substituted with a moiety belonging to R12 or R13. As used herein, "prodrug" means compounds that are drug precursors which, following administration to a patient, release the drug in vivo via some chemical or physiological process (e.g., a prodrug on being brought to the physiological pH or through enzyme action is converted to the desired drug form). Also included in the invention are tautomers, rotamers, enantiomers and other optical isomers, as well as prodrugs, of compounds of Formula I, as well as pharmaceutical^ acceptable salts, solvates and derivatives thereof. A further feature of the invention is pharmaceutical compositions containing as active ingredient a compound of Formula I (or its salt, solvate or isomers) together with a pharmaceutical^ acceptable carrier or excipient The invention also provides methods for preparing compounds of Formula l, as well as methods for treating diseases such as, for example, HCV, AIDS (Acquired Immune Deficiency Syndrome), and related disorders. The methods for treating comprise administering to a patient suffering from said disease or diseases a therapeutically effective amount of a compound of Formula I, or pharmaceutical compositions comprising a compound of Formula I. Also disclosed is the use of a compound of Formula I for the manufacture of a medicament for treating HCV, AIDS, and related disorders. Also disclosed is a method of treatment of a hepatitis C virus associated disorder, comprising administering an effective amount of one or more of the inventive compounds. Also disclosed is a method of modulating the activity of hepatitis C virus (HCV) protease, comprising contacting HCV protease with one or more inventive compounds. Also disclosed is a method of treating, preventing, or ameliorating one or more symptoms of hepatitis C, comprising administering an effective amount of one or more of the inventive compounds. The HCV protease is the NS3 or NS4a protease- The inventive compounds inhibit such protease. They also modulate the processing of hepatitis C virus (HCV) polypeptide. Detailed description of preferred embodiments In one embodiment, the present invention discloses compounds of Formula I as inhibitors of HCV protease, especially the HCV NS3/NS4a"serine protease, or a pharmaceutical^ acceptable derivative thereof, where the various definitions are given above. Representative compounds of the invention which exhibit excellent HCV protease inhibitory activity are listed below in Tables 1 to 5 along with their activity (ranges of Ki* values in nanomolar, nM). Several compounds as well as addiitonal compounds are additionally disclosed in the Claims. HCV continuous assay Ki* range: Category A = 1-100 nM; Category B = 101-1,000 nM; Category C >1000 nM. Some of the types of the inventive compounds and methods of synthesizing the various types of the inventive compounds of Formula I are listed below, then schematically described, followed by the illustrative Examples. Depending upon their structure, the compounds of the invention may form pharmaceutical^ acceptable salts with organic or inorganic acids, or organic or inorganic bases. Examples of suitable acids for such salt formation are hydrochloric, sulfuric, phosphoric, acetic, citric, malonic, salicylic, malic, fumaric, succinic, ascorbic, maleic, methanesulfonic and other mineral and carboxylic acids well known to those skilled in the art. For formation of salts with bases, suitable bases are, for example, NaOH, KOH, NH4OH, tetraalkylammonium hydroxide, and the like. In another embodiment, this invention provides pharmaceutical compositions comprising the inventive peptides as an active ingredient. The pharmaceutical compositions generally additionally comprise a pharmaceutically acceptable carrier diluent, excipient or carrier (collectively referred to herein as carrier materials). Because of their HCV inhibitory activity, such pharmaceutical compositions possess utility in treating hepatitis C and related disorders. In yet another embodiment, the present invention discloses methods for preparing pharmaceutical compositions comprising the inventive compounds as an active ingredient. In the pharmaceutical compositions and methods of the present invention, the active ingredients will typically be administered in admixture with suitable carrier materials suitably selected with respect to the intended form of administration, i.e. oral tablets, capsules (either solid-filled, semi-solid filled or liquid filled), powders for constitution, oral gels, elixirs, dispersible granules, syrups, suspensions, and the like, and consistent with conventional pharmaceutical practices. For example, for oral administration in the form of tablets or capsules, the active drug component may be combined with any oral non-toxic pharmaceutically acceptable inert carrier, such as lactose, starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, fa ale, mannitol, ethyl alcohol (liquid forms) and the like. Moreover, when desired or needed, suitable binders, lubricants, disintegrating agents and coloring agents nay also be incorporated in the mixture. Powders and tablets may be comprised Df from about 5 to about 95 percent inventive composition. Suitable binders include starch, gelatin, natural sugars, com sweeteners, natural and synthetic gums such as acacia, sodium alginate, carboxymethylcellulose, polyethylene glycol and waxes. Among the lubricants there may be mentioned for use in these dosage forms, boric acid, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include starch, methylcellulose, guar gum and the like. Sweetening and flavoring agents and preservatives may also be included where appropriate. Some of the terms noted above, namely disintegrants, diluents, lubricants, binders and the like, are discussed in more detail below. Additionally, the compositions of the present invention may be formulated in sustained release form to provide the rate controlled release of any one or more of the components or active ingredients to optimize the therapeutic effects, i.e. HCV inhibitory activity and the like. Suitable dosage forms for sustained release include layered tablets containing layers of varying disintegration rates or controlled release polymeric matrices impregnated with the active components and shaped in tablet form or capsules containing such impregnated or encapsulated porous polymeric matrices. Liquid form preparations include solutions, suspensions and emulsions. As an example may be mentioned water or water-propylene glycol solutions for parenteral injections or addition of sweeteners and pacifiers for oral solutions, suspensions and emulsions. Liquid form preparations may also include solutions for intranasal administration. Aerosol preparations suitable for inhalation may include solutions and solids in powder form, which may be in combination with a pharmaceutical^ acceptable carrier such as inert compressed gas, e.g. nitrogen. For preparing suppositories, a low melting wax such as a mixture of fatty acid glycerides such as cocoa butter is first melted, and the active ingredient is dispersed homogeneously therein by stirring or similar mixing. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool and thereby solidify. Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for either oral or parenteral administration. Such liquid forms include solutions, suspensions and emulsions. The compounds of the invention may also be deliverable transdermally. The transdermal compositions may take the form of creams, lotions, aerosols and/or emulsions and can be included in a transdermal patch of the matrix or reservoir type as are conventional in the art for this purpose. Preferably the compound is administered orally, intravenously or subcutaneously. Preferably, the pharmaceutical preparation is in a unit dosage form. In such form, the preparation is subdivided into suitably sized unit doses containing appropriate quantities of the active components, e.g., an effective-amount to achieve the desired purpose. The quantity of the inventive active composition in a unit dose of preparation may be generally varied or adjusted from about 1.0 milligram to about 1,000 milligrams, preferably from about 1.0 to about 950 milligrams, more preferably from about 1.0 to about 500 milligrams, and typically from about 1 to about 250 milligrams, according to the particular application. The actual dosage employed may be varied depending upon the patient's age, sex, weight and severity of the condition being treated. Such techniques are well known to those skilled in the art. Generally, the human oral dosage form containing the active ingredients can be administered 1 or 2 times per day. The amount and frequency of the administration will be regulated according to the judgment of the attending clinician. A generally recommended daily dosage regimen for oral administration may range from about 1.0 milligram to about 1,000 milligrams per day, in single or divided doses. Some useful terms are described below: Capsule - refers to a special container or enclosure made of methyl cellulose, polyvinyl alcohols, or denatured gelatins or starch for holding or containing compositions comprising the active ingredients. Hard shell capsules are typically made of blends of relatively high gel strength bone and pork skin gelatins. The capsule itself may contain small amounts of dyes, opaquing agents, plasticizers and preservatives-Tablet- refers to a compressed or molded solid dosage form containing the active ingredients with suitable diluents. The tablet can be prepared by compression of mixtures or granulations obtained by wet granulation, dry granulation or by compaction. Oral gel- refers to the active ingredients dispersed or solubilized in a hydrophillic semi-solid matrix. Powder for constitution refers to powder blends containing the active ingredients and suitable diluents which can be suspended in water or juices. Diluent - refers to substances that usually make up the major portion of the composition or dosage form. Suitable diluents include sugars such as lactose, sucrose, mannitol and sorbitol; starches derived from wheat, com, rice and potato; and celluloses such as microcrystalline cellulose. The amount of diluent in the composition can range from about 10 to about 90% by weight of the total composition, preferably from about 25 to about 75%, more preferably from about 30 to about 60% by weight, even more preferably from about 12 to about 60%. Disintegrant - refers to materials added to the composition to help it break apart (disintegrate) and release the medicaments. Suitable disintegrants include starches; "cold water soluble" modified starches such as sodium carboxymethyl starch; natural and synthetic gums such as locust bean, karaya, guar, tragacanth and agar; cellulose derivatives such as methylcellulose and sodium carboxymethylcellulose; microcrystalline celluloses and cross-linked microcrystalline celluloses such as sodium croscarmellose; alginates such as alginic acid and sodium alginate; clays such as bentonites; and effervescent mixtures. The amount of disintegrant in the composition can range from about 2 to about 15% by weight of the composition, more preferably from about 4 to about 10% by weight. Binder - refers to substances that bind or "glue" powders together and make them cohesive by forming granules, thus serving as the "adhesive" in the formulation. Binders add cohesive strength already available in the diluent or bulking agent. Suitable binders include sugars such as sucrose; starches derived from wheat, com rice and potato; natural gums such as acacia, gelatin and tragacanth; derivatives of seaweed such as alginic acid, sodium alginate and ammonium calcium alginate; cellulosic materials such as methylcellulose and sodium carboxymethylcellulose and hydroxypropylmethylcellulose; polyvinylpyrrolidone; and inorganics such as magnesium aluminum silicate. The amount of binder in the composition can range from about 2 to about 20% by weight of the composition, more preferably from about 3 to about 10% by weight, even more preferably from about 3 to about 6% by weight. Lubricant - refers to a substance added to the dosage form to enable the tablet, granules, etc. after it has been compressed, to release from the mold or die by reducing friction or wear. Suitable lubricants include metallic stearates such as magnesium stearate, calcium stearate or potassium stearate; stearic acid; high melting point waxes; and water soluble lubricants such as sodium chloride, sodium benzoate, sodium acetate, sodium oleate, polyethylene glycols and d'l-leucine. Lubricants are usually added at the very last step before compression, since they must be present on the surfaces of the granules and in between them and the parts of the tablet press. The amount of lubricant in the composition can range from about 0.2 to about 5% by weight of the composition, preferably from about 0.5 to about 2%, more preferably from about 0.3 to about 1.5% by weight. Glident - material that prevents caking and improve the flow characteristics of granulations, so that flow is smooth and uniform. Suitable glidents include silicon dioxide and talc. The amount of glident in the composition can range from about 0.1 % to about 5% by weight of the total composition, preferably from about 0.5 to about 2% by weight. Coloring agents - excipients that provide coloration to the composition or the dosage form. Such excipients can include food grade dyes and food grade dyes adsorbed onto a suitable adsorbent such as clay or aluminum oxide. The amount of the coloring agent can vary from about 0.1 to about 5% by weight of the composition, preferably from about 0.1 to about 1%. Bioavailability - refers to the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed into the systemic circulation from an administered dosage form as compared to a standard or control. Conventional methods for preparing tablets are known. Such methods include dry methods such as direct compression and compression of granulation produced by compaction, or wet methods or other special procedures. Conventional methods for making other forms for administration such as, for example, capsules, suppositories and the like are also well known. Another embodiment of the invention discloses the use of the pharmaceutical compositions disclosed above for treatment of diseases such as, for example, hepatitis C and the like. The method comprises administering a therapeutically effective amount of the inventive pharmaceutical composition to a patient having such a disease or diseases and in need of such a treatment In yet another embodiment, the compounds of the invention may be used for the treatment of HCV in humans in monotherapy mode or in a combination therapy (e.g., dual combination, triple combination etc.) mode such as, for example, in combination with antiviral and/or immunomodulatory agents. Examples of such antiviral and/or immunomodulatory agents include Ribavirin (from Schering-Plough Corporation, Madison, New Jersey) and Levovirin™ (from ICN Pharmaceuticals, Costa Mesa, California), VP 50406™ (from Viropharma, Incorporated, Exton, Pennsylvania), ISIS 14803™ (from ISIS Pharmaceuticals, Carlsbad, California), Heptazyme™ (from Ribozyme Pharmaceuticals, Boulder, Colorado), VX 497™ (from Vertex Pharmaceuticals, Cambridge, Massachusetts), Thymosin™ (from SciClone Pharmaceuticals, San Mateo, California), Maxamine™ (Maxim Pharmaceuticals, San Diego, California), mycophenolate mofetil (from Hoffman-LaRoche, Nutley, New Jersey), interferon (such as, for example, interferon-alpha, PEG-interferon alpha conjugates) and the like, "PEG-interferon alpha conjugates" are interferon alpha molecules covalently attached to a PEG molecule. Illustrative PEG-interferon alpha conjugates include interferon alpha-2a (Roferon™, from Hoffman La-Roche, Nutley, New Jersey) in the form of pegylated interferon alpha-2a (e.g., as sold under the trade name Pegasys™), interferon alpha-2b (Intron™, from Schering-Plough Corporation) in the form of pegylated interferon alpha-2b (e.g., as sold under the trade name PEG-lntron™), interferon alpha-2c (Berofor Alpha™, from Boehringer Ingelheim, Ingelheim, Germany) or consensus interferon as defined by determination of a consensus sequence of naturally occurring interferon alphas (Infergen™, from Amgen, Thousand Oaks, California). As stated earlier, the invention includes tautomers, rotamers, enantiomers and other stereoisomers of the inventive compounds also. Thus, as one skilled in the art appreciates, some of the inventive compounds may exist in suitable isomeric forms. Such variations are contemplated to be within the scope of the invention. Another embodiment of the invention discloses a method of making the compounds disclosed herein. The compounds may be prepared by several techniques known in the art. Representative illustrative procedures are outlined in the following reaction schemes. It is to be understood that while the following illustrative schemes describe the preparation of a few representative inventive compounds, suitable substitution of any of both the natural and unnatural amino acids will result in the formation of the desired compounds based on such substitution. Such variations are contemplated to be within the scope of the invention. Abbreviations which are used in the descriptions of the schemes, preparations and the examples that follow are: THF: Tetrahydrofuran DMF: A/,A/-Dimethylformamide EtOAc: Ethyl acetate AcOH: Acetic acid HOOBt: 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one EDCI: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride NMM: /V-Methylmorpholine ADDP: 1 T1'-(Azodicarbobyl)dipiperidine DEAD: Diethylazodicarboxylate MeOH: Methanol EtOH: Ethanol Et20: Diethyl ether DMSO: Dimethylsulfoxide HOBt: N-Hydroxybenzotriazoie PyBrOP: Bromo-fr/s-pyrrolidinophosphonium hexafluorophosphate DCM: Dichloromethane DCC: 1,3-Dicyclohexylcarbodiimide TEMPO: 2,2,6,6-Tetramethyl-1-piperidinyloxy Phg: Phenylglycine Chg: Cyclohexylglycine Bn: Benzyl Bzl: Benzyl Et: Ethyl Ph: Phenyl iBoc: isobutoxycarbonyl iPr: isopropyl *Bu or Bu*: terf-Butyi Boc: tert-Butyloxycarbonyl Cbz: Benzyloxycarbonyl Cp: Cylcopentyldienyl Ts: p-toluenesulfonyl Me: Methyl HATU: 0-(7-azabenzotriazol-1-yi)-1,1,3,3-tetramethyluronium hexafluorophosphate DMAP: 4-N,N-DimethyIaminopyridine Bop: BenzotriazoM -yl-oxy4ris(dimethylamino)hexafluorophosphate General Preparative Schemes: The following schemes describe the methods of synthesis of intermediate building blocks: Preparation of Intermediates: Preparative Example 1 Step A: Compound (1.1) To a stirred solution of Compound (1.08)(3.00 g, 12.0 mmol (S. L Harbeson et at. J.Med.Chem. 37 No. 18 (1994) 2918-2929) in DMF (15 mL) and CH2CI2 (15 mL) at -20°C was added HOOBt (1.97 g, 12.0 mmol), /V-methyl morpholine (4.0 mL, 36.0 mmol) and EDCI (2.79 g, 14.5 mmol) and stirred for 10 minutes, followed by addition of HCI-hfeN-Gly-OBn (2.56 g, 13.0 mmol). The resulting solution was stirred at -20°C for 2 hrs, kept refrigerated overnight and then concentrated to dryness, followed by dilution with EtOAc (150 mL). The EtOAc solution was then washed twice with saturated NaHC03, H20, 5% H3PO4, brine, dried over Na2S04, filtered and concentrated to dryness to give the Compound (1.09) (4.5 g, 94%). LRMS m/z MH+= 395.1. Step B: Compound (1.1) A solution of Compound (1.09) (7.00 g, 17.8 mmol) in absolute ethanol (300 mL) was stirred at room temperature under a hydrogen atmosphere in the presence of Pd-C (300 mg, 10%). The reaction progress was monitored by tic. After 2 h, the mixture was filtered through a celite pad and the resulting solution was concentrated in vacuo to give Compound (1.1) (5.40 g, quantitative). LRMS m/zMH+= 305.1. Preparative Example 2 Step A Compound (1,31 (1.1) (1.2) (1.3) A mixture of Compound (1.1) from Preparative Example 1, Step B above (1 eq.), Compound (1.2) (from Novabiochem, Catalog No. 04-12-5147) (1.03 eq.), HOOBt (1.03 eq.), N-methylmorpholine (2.2 eq.), and dimethylformamide (70 mUg) was stirred at -20°C. EDCI (1.04 eq.) was added and the reaction stirred for 48 hr. The reaction mixture was poured into 5% aqueous KH2PO4 and extracted with ethyl acetate (2 x). The combined organics were washed with cold 5% aqueous K2CO3, then 5% aqueous KH2PO4, then brine, and the organic layer was dried over anhydrous MgS04- The mixture was filtered, then evaporated and the filtrate dried under vacuum, the residue was triturated with Et20-hexane, and filtered to leave the title compound (1.3)(86% yield), C25H39N3O7 (493.60), mass spec. (FAB) M+1 = 494.3. SteoB Compound (1.4) Compound (1.3) from Preparative Example 2, Step A (3.0 g) was treated with 4 N HCI/dioxane (36 mL) and stirred at room temperature for 7 min. The mixture was poured into 1.5 L cold (5°C) hexane and stirred, then allowed to set cold for 0.5 hr. The mixture was suction-filtered in a dry atmosphere, and the collected solid was further dried to afford the title compound (1.4) (2.3 g, 88% yield), C20H31N305-HCI, H1 NMR (DMSO-d6/NaOD) 5 7.38 (m, 5H), 5.25 (m, 1H), 4.3-4.1 (m, 1H), 3.8 (m, 2H), 3.4-3.3 (m, obscured by D2O), 1.7-1.1 (m, 4H), 1.35 (s,9H), 0.83 (m,3H). Preparative Example 3 Compound (1.5) Compound (1.3) from Preparative Example 2, Step A, was treated in essentially the same manner as in Preparative Example 7, Step A below to afford Compound (1.5). Preparative Example 4 Compound (1.6) Compound (1.5) from Preparative Example 3, was treated in essentially the same manner as in Preparative Example 2, Step B, to afford Compound (1.6). Preparative Example 5 Step A Compound (2.09) To a solution of dimethylamine hydrochloride (1.61 gf 19.7 mmol), A/-B00 phenylglycine, Compound (2.08)(4.50 g, 17-9 mmol, Bachem Co. # A-2225), HOOBt (3.07 g, 18.8 mmol) and EDCI (4.12 g, 21.5 mmol) in anhydrous DMF (200 mL) and CH2CI2 (150 mL) at -20°C was added NMM (5.90 mL, 53.7 mmol). After being stirred at this temperature for 30 min, the reaction mixture was kept in a freezer overnight (18 h). It was then allowed to warm to rt, and EtOAc (450 mL), brine (100 mL) and 5% H3PO4 (100 mL) were added. After the layers were separated, the organic layer was washed with 5% H3PO4 (100 mL), saturated aqueous sodium bicarbonate solution (2 X 150 mL), water (150 mL), and brine (150 mL), dried (MgS04), filtered and concentrated in vacuo to afford Compound (2.09) (4.86 g) as a white solid, which was used without further purification. StepB Compound (2.1) Compound (2.09) from Preparative Example 5, Step A (4.70 g, crude) was dissolved in 4 N HCI (60 mL, 240 mmol) and the resulting solution was stirred at room temperature. The progress of the reaction was monitored by TLC. After 4 h, the solution was concentrated in vacuo to yield Compound (2.1) as a white solid which was used in the next reaction without further purification. LRMS m/z MH+= 179.0. Preparative Example 6 Step A Compound (2.2) In essentially the same manner as Preparative Example 2, Step A. substituting phenylglycine N,N-dimethylamide hydrochloride in place of phenylglycine f-butyl ester hydrochloride, Compound (2.2) was prepared mass spec. (FAB) M+1 = 465.3. StepB Compound (2.3) Compound (2.2) from Step A (1.85 g) was reacted with 4 N HCI/dioxane (50 mL) at room temperature for 1 hr. The mixture was evaporated under vacuum in a 20°C water bath, triturated under isopropyi ether, filtered, and dried to afford Compound (2.3) (1.57 g, 98% yield), C-|8H28N404'HCI, mass spec. (FAB) M+1 = 365.3 Preparative Example 7 Step A Compound (2.4) (2.2) (2.4) A solution of Compound (2.2) from Preparative Example 5, Step A (2.0 g) in dichioromethane (60 mL) was treated with dimethylsulfoxide (3.0 mL) and 2,2-dichloroacetic acid (0.70 mL). The stirred mixture was cooled to 5°C and then added 1 M dicyclohexylcarbodiimide/ dichioromethane solution (8.5 mL). The cold bath was removed and the mixture stirred for 22 hr. Then added 2-propanol (0.5 mL), and stirred for an additional 1 hr. The mixture was filtered then washed with ice-cold 0.1 N NaOH (50mL), then ice-cold 0.1 N HCI (50 mL), then 5% aqueous KH2PO4, then saturated brine. The organic solution was dried over anhydrous magnesium sulfate, then filtered. The filtrate was evaporated, and chromatographed on silica gel, eluting with ethyl acetate to afford Compound (2.3) (1.87 g, 94% yield), C23H34N4O6 , mass spec. (FAB) M+1 = 463.3. StepB Compound (2.5) In essentially the same manner as Preparative Example 2, Step B, Compound (2.5) was prepared. Preparative Example 8 Step A Compound (3.1) In a flask were combined N-Cbz-hydroxyproline methyl ester (available from Bachem Biosciences, Incorporated, King of Prussia, Pennsylvania), compound (3.01) (3.0 g), toluene (30 mL), and ethyl acetate (30 mL). The mixture was stirred vigorously, and then a solution of NaBr/water (1.28 g /5 mL) was added. To this was added 2,2,6,6-tetramethyM-piperidinyIoxy free radical (TEMPO, 17 mg, from Aldrich Chemicals, Milwaukee, Wisconsin). The stirred mixture was cooled to 5°C and then was added a prepared solution of oxidant [commercially available bleach, Clorox® (18 mL), NaHC03 (275 g) and water to make up 40 mL] dropwise over 0.5 hr. To this was added 2-propanol (0.2 mL). The organic layer was separated, and the aqueous layer extracted with ethyl acetate. The organic extracts were combined, washed with 2% sodium thiosulfate, then saturated brine. The organic solution was dried over anhydrous MgS04, filtered, and evaporated the filtrate under vacuum to leave a pale yellow gum suitable for subsequent reactions (2.9 g, 97% yield), C14H15NO5 (277.28), mass spec. (FAB) M+1 =278.1. StepB Compound (3.2V Compound (3.1) from Step A above (7.8 g) was dissolved in dichloromethane (100 mL), and cooled to 15°C. To this mixture was first added 1,3-propanedithiol (3.1 mL), followed by freshly distilled boron trifluoride etherate (3.7 mL). The mixture was stirred at room temperature for 18 h. While stirring vigorously, a solution of K2C03/water (2 g / 30 mL)was carefully added, followed by saturated NaHC03 (10 mL), The organic layer was separated from the aqueous layer (pH -7.4), washed with water (10 mL), then brine. The organic solution was dried over anhydrous MgS04, filtered, and evaporated under vacuum. The residue was chromatographed on silica gel, eluting with toluene, then a with a gradient of hexane-Et20 (2:3 to 0:1) to afford a brown oil (7.0 g, 68% field), C17H21NO4S2 (367.48), mass spec. (FAB) M+1 =368.1. 3tepC Compound (3.3) A solution of compound (3.2) from Step B above (45 g) in acetonitrile (800 rnL) at 20°C was treated with freshly distilled iodotrimethylsilane (53 mL) at once. The reaction was stirred for 30 min., then poured into a freshly prepared solution Df di-t-butyldicarbonate (107 g), ethyl ether (150 mL), and diisopropylethylamine (66.5 mL). The mixture stirred for 30 min. more then was washed with hexane (2 x 500 mL). Ethyl acetate (1000 mL) was added to the lower acetonitrile layer, and then the layer was washed with 10% aqueous KH2PO4 (2 x 700 mL), and brine. The filtrate was evaporated under vacuum in a 25°C water bath, taken up in fresh ethyl acetate (1000 mL), and washed successively with 0.1 N HCI, 0.1 N IMaOH, 10% aqueous KH2PO4, and brine. The organic solution was dried over anhydrous MgS04, filtered, and evaporated under vacuum. The residue (66 g) was chromatographed on silica gel (2 kg), eluting with hexane (2 L), then Et20/hexane (55:45, 2 L), then Et20 (2 L) to afford an orange gum which slowly crystallized on standing (28 g, 69% yield), C14H23NO4S2 (333.46), mass spec. (FAB) M+1 =334.1. StepD Compound (3.4^ A solution of compound (3.3) from Step C above (11 g) in dioxane (150 mL) at 20°C was treated with 1N aqueous LiOH (47 mL) and stirred for 30 h. The mixture was concentrated under vacuum in a 30°C water bath to half volume. The remainder was diluted with water (300 mL), extracted with Et20 (2 x 200 mL). The aqueous layer was acidified to pH ~4 with 12 N HCI (3-4 mL), extracted with ethyl acetate, and washed with brine. The organic solution was dried over anhydrous MgS04, filtered, and evaporated under vacuum to leave Compound (3.4) (8.1 g, 78%), C13H21NO4S2 (319.44), mass spec. (FAB) M+1 = 320.1. Step E Compound (3.5V To a solution of compound (3,3) from Step C above (1 g> in dioxane (5 mL), was added 4 N HCI-dioxane solution (50 mL). The mixture was stirred vigorously for 1 hr. The mixture was evaporated under vacuum in a 25°C water bath. The residue was triturated with Et20, and filtered to leave the title compound (0.76 g, 93% yield), C9H15N02S2-HCI (269.81), mass spec. (FAB) M+1 = 234.0. Preparative Example 9 Step A Compound (3.6) Following essentially the same procedure of Preparative Example 8, Step B, substituting ethane dithiol for propane dithiol, compound (3.6) was obtained. SteoB Compound (3.7). Following essentially the same procedure of Preparative Example 8, Step C, substituting compound (3.6) for compound (3.2), the product compound (3.7) was obtained. StepC Compound (3.8) Following essentially the same procedure of Preparative Example 8, Step D, substituting compound (3.7) for compound (3.3) the product compound (3.8) was obtained. StepD Compound (3.9) Following essentially the same procedure of Preparative Example 8, Step E, substituting compound (3.7) for compound (3.3) the product compound (3.9) was obtained. Preparative Example 10 Step A Compound (4.1) In essentially the same manner as Preparative Example 2, Step A, Compound (4.1) was prepared C33H48N40gS2 (708.89). StepB Compound (4.2) In essentially the same manner as Preparative Example 2, Step B, Compound (4.2) was prepared mass spec. (FAB) M+1 = 609.3. StepC Compound (4.3) 4 Compound (4.9) from Preparative Example 12, was reacted with Compound (4.6) from Step B above, in essentially the same manner as Preparative Example 2, Step A, to afford Compound (4.7). Step D, Compound (4.8) In essentially the same manner as Preparative Example 7, Step A, Compound (4.8) was prepared. Preparative Example 12 Compound (4.9) /-BuOCOCI + H-Chg-OH *- IbocrChg-OH (4.01) (4.02) (4.9) A solution of L-cydohexylglycine (4.02) (1.0 eq.), dimethylformamide (20 mL/g), and diisopropylethylamine (1.1 eq.) at 5°C is treated with isobutyl chloroformate (4.01) (1.1 eq.). The cold bath is removed and it is stirred for 6 hr. The reaction mixture is poured into 5% aqueous KH2PO4 and extracted with ethyl acetate (2 x). The combined organics are washed with cold 5% aqueous K2C03, then 5% aqueous KH2PO4, then brine, and the organics are dried over anhydrous MgSO-4. The mixture is filtered, the filtrate evaporated under vacuum, the residue chromatographed if necessary or else the residue triturated with Et20-hexane, and filtered to leave the title compound (4.9), C13H23NO4 (257.33). Preparative Example 13 Compound (13.1) /-BuOCOCI + H-Thr(Bzl)-OH —*- lboc-Thr(BzI)-OH (4.01) (13.02) (13.1) In essentially the same manner as Preparative Example 12, substituting L-O-benzylthreonine (13.02) (Wang et al, J. Chem. Soc, Perkin Trans. 1, (1997) No. 5, 621-624.) for L-cyclohexylglycine (4.02) Compound (13.1) is prepared C16H23NO5 (309.36), mass spec. (FAB) M+1 = 310.2. ■ Preparative Example 14 Compound (4.8) from Preparative Example 11, Step D (1.0 g) was reacted with a solution of anhydrous trifluoroacetic acid-dichloromethane (1:1, 50 mL) for 2 hr. The solution was diluted with xylene (100 mL) and evaporated under vacuum. The residue was triturated with Et20, and filtered to leave the title compound (5.1) (0.9 g), C37H53N5O9S2 (775.98), mass spec. (FAB) M+1 =776.5. StepB Compound (5.2) In essentially the same manner as Preparative Example 2, Step A, Compound (5,1) was reacted with ammonia (0.5 M 1,4-dioxane solution), to obtain the title compound (5.2) C37H54N6O8S2 (774.99), mass spec. (FAB) M+l = 775.4. Preparative Example 15 A mixture of Compound (5.1) from Preparative Example 14, Step A (0.15 g), N,N-dimethylamine (0.12 mL of 2 M THF solution), dimethylformamide (10 mL), and PyBrOP coupling reagent (0.11 g) was cooled to 5°C, then diisopropylethylamine (DIEA or DIPEA, 0.12 mL) was added. The mixture was stirred cold for 1 min., then stirred at room temperature for 6 hr. The reaction mixture was poured into cold 5% aqueous H3PO4 (50 mL) and extracted with ethyl acetate (2 x). The combined organics were washed with cold 5% aqueous K2CO3, then 5% aqueous KH2P04, then brine. The organic solution was dried over anhydrous MgS04, filtered, and evaporated under vacuum. The residue was chromatographed on silica gel, eluting with MeOH-CH2Cl2 to afford the title compound (5.3), C39H58N6O8S2 (803.05), mass spec. (FAB) M+1 =803.5. * * Preparative Example 16 Step A Compound (6.2) In essentially the same manner as Preparative Example 2, Step A, Compound (6.1) hydroxyproline benzyl ester hydrochloride was reacted with Compound (4.9) from Preparative Example 12, to obtain the title compound (6.2), C25H36N2O6 (460.56), mass spec. (FAB) M+1 = 461.2. StepB Compound (6.3) In essentially the same manner as Preparative Example 8, Compound (6.3) was prepared, C25H34N2O6 (458.55), mass spec. (FAB) M+1 = 459.2. StepC Compound (6.4) (6.3) (6.4) A mixture of Compound (6.3) from Step B (1 g), 10% Pd/C (0.05 g), and EtOH (100 mL) was stirred under 1 atm. H2 for 6 hr. The mixture was filtered, and evaporated to dryness under vacuum to leave the title compound (6.4) (0.77 g), C18H28N2O6 (368.42) mass spec. (FAB) M+1 = 369.2. Preparative Example 17 Step A Compound (7.1) (7.1) Compound (6.4) from Preparative Example 16, Step C, was reacted with Compound (2.3) from Preparative Example 6, Step B, in essentially the same manner as Preparative Example 2, Step A, to afford Compound (7.1), C36H54N6O9 (714.85), mass spec. (FAB) M+1 = 715.9. StepB Compound (7.2) Compound (7,1) was reacted in essentially the same manner as Preparative Example 7, Step A, to afford Compound (7.2), C36H52N6O9 (712.83), mass spec. (FAB) M+1 =713.5. StepC Compound (7.3) Compound (7.2) from Step B above, was reacted in essentially the same manner as Preparative Example 8, Step B, with 1,4-butanedithiol, to obtain the title compound (7.3), C40H6ON6O8S2 (817.07), mass spec. (FAB) M+1 = 817.5. Using the above-noted procedures, the compounds in the attached Table 2 were prepared. As a general note to all the Tables that are attached hereto as well as to the Examples and Schemes in this specification, any open-ended nitrogen atom with unfulfilled valence in the chemical structures in the Examples and Tables refers to NH, or in the case of a terminal nitrogen, -NH2. Similarly, any open-ended oxygen atom with unfulfilled valence in the chemical structures in the Examples and Tables refers to -OH. Solid Phase Synthesis: General procedure for solid-phase coupling reactions. The synthesis was done in a reaction vessel which was constructed from a polypropylene syringe cartridge fitted with a polypropylene frit at the bottom. The Fmoc-protected amino acids were coupled under standard solid-phase techniques. Each reaction vessel was loaded with 100 mg of the starting Fmoc-Sieber resin (approximately 0.03 mmol). The resin was washed with 2 mL portions of DMF (2 times). The Fmoc protecting group was removed by treatment with 2 mL of a 20 % v/v solution of piperidine in DMF for 20 min. The resin was washed with 2 mL portions of DMF (4 times). The coupling was done in DMF (2 mL), using 0.1 mmol of Fmoc-amino acid, 0.1 mmol of HATU [ 0-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate ] and 0.2 mmol of DIPEA (N,N-diisopropylethylamine). After shaking for 2 h, the reaction vessel was drained and the resin was washed with 2 mL portions of DMF (4 times). The coupling cycle was repeated with the next Fmoc-amino acid or capping group. General procedure for solid-phase Dess-Martin oxidation. The synthesis was conducted in a reaction vessel which was constructed from a polypropylene syringe cartridge fitted with a polypropylene frit at the bottom. Resin-bound hydroxy compound (approximately 0.03 mmol) was treated with a solution of 0.12 mmol of Dess-Martin periodinane and 0.12 mmol of t-BuOH in 2 ml_ of DCM for 4 h. The resin was washed with 2 ml_ portions of a 20 % v/v solution of iPrOH in DCM, THF, a 50 % v/v solution of THF in water (4 times), THF (4 times) and DCM (4 times). Preparative Example 18 Preparation of N-Fmoc-2\3'-dimethoxvphenvlalvcine Compound (901) OMe 901 To a solution of potassium cyanide (1.465 g, 22.5 rnmol) and ammonium carbonate (5.045 g, 52.5 rnmol) in water (15 mL) was added a solution of 2,3-dimethoxybenzaldehye 901A (2.5 g, 15 rnmol) in ethanol (15 mL). The reaction mixture was heated at 40 °C for 24 h. The volume of the solution was reduced to 10 mL by evaporating under reduced pressure. Concentrated hydrochloric acid (15 mL) was added and compound 901B was obtained as a white precipitate. Compound 901B was isolated by filtration (2.2 g, 9.3 rnmol). Compound 901B was dissolved in 10 % w/w aqueous sodiifm hydroxide solution (15 mL) and the resulting solution was heated under reflux for 24 h. Concentrated hydrochloric acid was added and the pH was adjusted to neutral (pH 7). The resulting solution containing compound 901C was evaporated under reduced pressure. The residue was dissolved in 5 % w/w aqueous sodium bicarbonate solution (150 mL). The solution was cooled to 0 °C in an ice bath and 1,4-dioxane (30 mL) and a solution of 9-fluorenylmethyl succinimidyl carbonate (2.7 g, 8 mmol) in 1,4-dioxane (30 mL) was added at 0 °C. The reaction mixture was allowed to warm to room temperature and was stirred at room temperature for 24 h. 1,4-dioxane was evaporated under reduced pressure. The aqueous solution was washed with diethyl ether. Concentrated hydrochloric acid was added and the pH was adjusted to acidic (pH 1). Ethyl acetate was added the organic layer was washed with water and brine. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afford the desired compound 901 as a white foamy solid (3.44 g, 7,9 mmol). MS (LCMS-Electrospray) 434.1 MH+. Preparative Example 19 Compound (801) To a solution of N-Fmoc-phenylalanine 801A (5 g, 12.9 mmol) in anhydrous DCM (22 mL) cooled to -30°C in a dry ice-acetone bath was added N-methylpyrrolidine (1.96 mL, 16.1 mmol) and methyl chloroformate (1.2 mL, 15.5 mmol) sequentially. The reaction mixture was stirred at -30°C for 1 h and a solution of N.O-dimethylhydroxylamine hydrochloride (1.51 g, 15.5 mol) and N-methylpyrrolidine (1.96 mL, 16.1 mmol) in anhydrous DCM (8 mL) was added. The reaction mixture was allowed to warm to room temperature and was stirred at room temperature overnight. Toluene was added and the organic layer was washed with dilute hydrochloric acid, aqueous sodium bicarbonate solution and brine. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afforded compound 801B (4 g, 9.29 mmol). To a solution of Red-AI (6.28 mL, 21.4 mmol) in anhydrous toluene (8 mL) cooled to -20°C in a dry ice-acetone bath was added a solution of compound 801B (4 g, 9.29 mmol) in anhydrous toluene (12 mL). The reaction mixture was stirred at-20 °C for 1.5 h. The organic layer was washed with dilute hydrochloric acid, aqueous sodium bicarbonate solution and brine. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the crude product 801C was used in the next reaction without further purification. To a solution of compound 801C (approx. 9.29 mmol) in hexane (15 mL) was added a solution of potassium cyanide (24 mg, 0.37 mmol) and tetrabutylammonium iodide (34 mg, 0.092 mmol) in water (4 mL) and acetone cyanohydrin (1.27 mL, 13.9 mmol) sequentially. The reaction mixture was stirred at room temperature for 24 h. Ethyl acetate was added and the organic layer was washed with water and brine. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afford compound 801D (2.4 gf 6.03 mmol). To a solution of compound 801D (2.4 g, 6.03 mmol) in 1,4-dioxane (11 mL) was added concentrated hydrochloric acid (11 mL). The reaction mixture was heated at 80 °C for 3 h. Ethyl acetate (25 mL) and water (25 mL) was added. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to afford the desired compound 801 as a white foamy solid (2 g, 4.8 mmol). MS (LCMS-Electrospray) 418.1 Mbf. Example (301 J): Scheme 8 Compound (301 J) (301J) Resin-bound compound 301B, 301C, 301D, 301E, 301F and 301G were prepared according to the general procedure for solid-phase coupling reactions started with 100 mg of Fmoc-Sieber resin (0.03 mmol). Resin-bound compound 301G was oxidized to resin-bound compound 301H according to the general procedure for solid-phase Dess-Martin oxidation. The resin-bound compound 301H was treated with 4 mL of a 2 % v/v solution of TFA in DCM for 5 min. The filtrate was added to 1 mL of AcOH and the solution was concentrated by vacuum centrifugation to provide compound 301J (0.0069 g, 29 % yield). MS (LCMS-Electrospray) 771.2 MH+. Using the solid phase synthesis techniques detailed above, and the following moieties for the various functionalities in the compound of Formula 1, the compounds in Table 3 were prepared: -W-: Y-W-: Additional compounds that were prepared and their activity (Ki*) ranges are given in the attached Tables 4 and 5. The procedure used to prepare the compounds in Tables 4 and 5 is outlined below. I) Synthesis of intermediates for the compounds in Tables 4 and 5: Example I. Synthesis of 4,4-dimethyl proline methyl ester (H-Pro(4,4-diMe)-OMe) Step 1. Synthesis of tert-Butvl N-tert-butoxvcarbonvl-4-methvl-L-DvroQlutamate (Boc-PvroGlu(4-methvlVOtBuV To a solution of tert-butyl N-tert-butoxycarbonyl-pyroglutamate (11.5 g, 40 mmol) in THF (200 mL) stirring at -78 °C, was added a 1M solution of lithium hexamethyldisilazide in THF (42 mL, 42 mmol) dropwise over 5 minutes. After 30 minutes, methyliodide (3.11 mL, 50 mmol) was added. After an additional 2 hours at -78 °C, the cooling bath was removed and 50% saturated aqueous ammonium chloride (200 mL) was added. The solution was stirred for 20 minutes, then extracted with ether (3 x 200 mL). The combined organic layers were washed with brine (200 mL), dried (Na2S04), filtered and concentrated. The residue was chromatographed with 1:1 ethylacetate/hexanes to give Boc-PyroGlu(4-methyl)-OtBu (10.6 grams, 35.4 mmol, 88%) as a mixture of isomers (2:1 cis to trans). Step 2. Synthesis of tert-Butvl N-tert-butoxvcarbonvl-4.4-dimethvl-L-Dvroalutamate (Boc-PvroGlu(4.4-dimethvn-OtBu): To a solution of tert-butyl N-tert-butoxycarbonyl-4-methyl-L-pyroglutamate (1.2 g, 4.0 mmol) in tetrahydrofuran (20 mL) stirring at -78 °C, was added a 1M solution of lithium hexamethyldisilazide in tetrahydrofuran (4.4 mL, 4.4 mmol) dropwise over 5 minutes. After 30 minutes, methyliodide (0.33 mL, 5.2 mmol) was added. After an additional 3 hours at -78 °C, the cooling bath was removed and 50% saturated aqueous ammonium chloride (40 mL) was added. The solution was stirred for 20 minutes, then extracted with ether (2 x 50 mL). The combined organic layers were washed with water(2 x 25 mL), saturated sodium bicarbonate (2 x 25 mL), brine (50 mL), dried (NaaSCU), filtered and concentrated to give Boc- PyroG!u(4,4-dimethyl)-OtBu (0.673 g, 54%). Step 3. Synthesis of tert-butvl N-tert-butoxvcarbonvl-4.4-dimethvlproline (Boc- Pro(4.4-dimethvllOtBu) Modification of known procedure: Pedregal, C; Ezquerra, J.; Escribano, A.; Carreno, M. C; Garcia Ruano, J'. L. Tetrahedron Letters 1994, 35(13), 2053-2056). To a solution of tert-butyl N-tert-butoxycarbonyl-4,4-dimethylpyroglutamate (2.0 mmol) in tetrahydrofuran (5 mL) stirring at -78 °C, was added a 1M solution of lithium triethylborohydride in tetrahydrofuran (2.4 mL, 2.4 mmol) dropwise over 5 minutes. After 30 minutes, the cooling bath was removed and saturated aqueous sodium bicarbonate (5 mL) was added. The reaction mixture was immersed in an ice/water bath and 30% aqueous hydrogen peroxide (10 drops) was added. The solution was stirred for 20 minutes at 0 °C, then the reaction mixture was concentrated in vacuo to remove the tetrahydrofuran. The aqueous solution was diluted with water (10 mL) and extracted with dichloromethane (3 x 40 mL). The organic layers were dried (Na2S04), filtered and concentrated. The residue was dissolved in dichloromethane (20 mL) and triethylsilane (310 ^L, 2.0 mmol), then cooled to -78 °C and boron trifluoride diethyletherate (270 nL, 2.13 mmol) was added dropwise. Stirring was continued for 30 minutes, at which time additional triethylsilane (310 ^L, 2.0 mmol) and boron trifluoride diethyletherate (270 |i!_, 2.13 mmol) were added. After stirring at -78 °C for an additional two hours, the cooling bath was removed and saturated aqueous sodium bicarbonate (4 mL) was added. After 5 minutes the mixture was extracted with dichloromethane (3 x 40 mL). The organic layers were dried (Na2S04), filtered and concentrated to give Boc-Pro(4,4-dimethyl)-OtBu. Step 4. Synthesis of 4,4-dimethvlproline (H-Pro(4.4-dimethvlVOH): A solution of tert-butyl N-tert-butoxycarbonyl-4,4-dimethylproline in dichloromethane (5 rriL) and trifluoroacetic (5 mL) was stirred at room temperature for five hours. The solution was concentrated, dried under high vacuum and taken to the next step without further purification. Step 5. Synthesis of N-tert-butoxvcarbonvl 4.4-dimethvlproline (Boc-Pro(4.4-dimethvlVOH): To a solution of 4,4-dimethylproline trifluoroacetic salt (1.5 mmol) in dioxane (7 mL), acetonitrile (12 mL) and diisopropylethylamine (700 ^L, 4 mmol) was added a solution of di-tert-butyl-dicarbonate (475 mg, 2.18 mmol) in acetonitrile (5 mL). After stirring for 12 hours at room temperature the solution was concentrated in vacuo, dissolved in saturated aqueous sodium bicarbonate (50 mL) and washed with diethyl ether (3 x 40 mL). The aqueous layer was acidified to pH=3 with citric acid, then extracted with dichloromethane (3 x 40 mL). The combined organic layers were dried over sodium sulfate filtered and concentrated. Step 6. Synthesis of 4.4-dimethvlproline methvlester hydrochloride salt (HOH- Pro(4.4-dimethylVOMe): To a solution of Boc-Pro(4,4-diMe)-OH (0.5 g, 2.06 mmol) in anhydrous methanol (8 ml) was added dropwise thionylchloride (448 I, 6,18 mmol) and the reaction was stirred for six hours at room temperature. The reaction mixture was concentrated to an amorphous solid (377 mg, 95%). Example II. General procedure for the synthesis of N-tertbutoxvcarbonvl-4-alkvl-4-methvl proline: Compounds where R group is allyl and benzyl were synthesized following steps 1-4 below: Step 1. Synthesis of tert-Butvl N-tert-butoxvcarbonvM-alkvl-4-methvl-L-pvroqlutamate: To a solution of tert-butyl N-tert-butoxycarbonyl-4-methyl-L-pyroglutamate (10.2 g, mmol) (see Example I, step 1) in tetrahydrofuran (170 mL) stirring at -78 °C, was added a 1M solution of lithium hexamethyldisilazide in tetrahydrofuran (37.5 mL, 37.5 mmol) dropwise over 5 minutes. After 40 minutes, alkyl halide (61.4 mmol) was added. After an additional 3 hours at -78 °C, the cooling bath was removed and 50% saturated aqueous ammonium chloride (200 mL) was added. The solution was stirred for 20 minutes, then extracted with ether (2 x 200 mL). The combined organic layers were diluted with hexanes (150 mL) and washed with saturated sodium bicarbonate (100 mL), water (2 x 100 mL) and brine (100 mL), dried (Na2S04), filtered and concentrated. The residue was flash chromatographed using 20% ethylacetate in hexanes to give the pure tert-Butyl N-tert-butoxycarbonyl-4-alkyl-4-methyl-L-pyroglutamate. Step 2, Synthesis of tert-butvl N-tert-butoxvcarbonvl-4-alkvl-4>methvlproline: Modification of known procedure: Pedregal, C; Ezquerra, J.; Escribano, A.; Carreno, M. C; Garcia Ruano, J. L. Tetrahedron Letters (1994) 35(13), 2053-2056). To a solution of tert-butyl N-tert-butoxycarbonyl-4-alkyl-4-methylpyroglutamate (16.6 mmol) in tetrahydrofuran (40 mL) stirring at -78 °C, was added a 1M solution of lithium triethylborohydride in tetrahydrofuran (20 mL, 20 mmol) dropwise over 10 minutes. After 120 minutes, the cooling bath was allowed to warm to -25 °C at which point saturated aqueous sodium bicarbonate (40 mL) was added. The reaction mixture was immersed in an ice/water bath and 30% aqueous hydrogen peroxide (4 mL) was added. The solution was stirred for 10 minutes at 0 °C, then the reaction mixture was concentrated in vacuo to remove the tetrahydrofuran. The aqueous solution was diluted with water (300 mL) and extracted with dichloromethane (3 x 200 mL). The organic layers were dried (sodium sulfate), filtered and concentrated. The residue was dissolved in dichloromethane (100 mL) and triethylsilane (2.6 mL, mmol), then cooled to -78 °C and boron trifluoride diethyietherate (2.2 mL, mmol) was added dropwise. Stirring was continued for 1 hour, at which time additional triethylsilane (2.6 mL, mmol) and boron trifluoride diethyietherate (2.2 mL, mmol) were added. After stirring at -78 °C for an additional 4 hours, the cooling bath was removed and saturated aqueous sodium bicarbonate (30 mL) and water (150 mL) were added. After 5 minutes the mixture was extracted with dichloromethane (3 x 200 mL). The organic layers were dried (Na2S04), filtered and concentrated. Step 3. Synthesis 4-alkvl-4-methvlproline: A solution of tert-butyl N-tert-butoxycarbonyl-4-alkyl-4-methylproline in dichloromethane (5 mL) and trifluoroacetic (5 mL) was stirred at room temperature for 5 hours. Toluene was added and the solution was concentrated and then dried under high vacuum. Step 4. Synthesis of N-tert-butoxvcarbonvl 4-alkvl-4-methvtproline: To a solution of 4-alkyi-4-methylproline trifluoroacetic salt (1.5 mmol) in dioxane (7 mL), acetonitrile (12 mL) and diisopropylethylamine (700 ^L, 4 mmol) was added a solution of di-tert-butyl-dicarbonate (475 mg, 2.18 mmol) in acetonitrile(5 mL). After stirring for 12 hours at room temperature the solution was concentrated in vacuo, dissolved in saturated aqueous sodium bicarbonate (50 mL) and washed with diethyl ether (3 x 40 mL). The aqueous layer was acidified to pH=3 with 1N hydrochloric acid, then extracted with dichloromethane (3 x 40 mL). The combined organic layers were dried (Na2S04), filtered and concentrated. The residue was purified by flash chromatography using 1:1 ethylacetate/hexanes with 1% acetic acid. Example III. Synthesis of N-tert-butoxvcarbonvl 4-propvl-4-methvlproline: A solution of N-tertbutoxycarbonyl-4-allyl-4-methylproline (400 mg, 1.48 mmol) (see Example II Step 4) and 10% Pd on carbon (400 mg) in methanol (20 mL) was hydrogenated at 50 psi for 4 hours. The mixture was filtered and concentrated. Example IV. Synthesis of Boc-4-cvclohexvlproline: A solution of the commercially available Boc-4-phenylproline (750 mg) and 5% Rh on carbon (750 mg) in methanol (15 mL) was hydrogenated at 50 psi for 24 hours. The mixture was filtered and concentrated to give 730 mg of product. Example V: Preparation of Fluorenvlmethoxvcarbonvl-Pro(4-spirocvclopentaneV carboxvlic acid : a Step 1. Synthesis of Boc-pvroaiutamic(4-allvlVtert-butvlester: To a cooled (-78 °C) solution of the commercially available N-Bo c-tert-butyl pyroglutamate (10 g, 35.1 mmol) in THF (175 ml) was added lithium hexamethyldisilazide (36.8 mL, 36.8 mmol) over five minutes. Stirring continued for thirty minutes. A solution of allyl bromide (6.1 ml, 70.2 mmol) in THF (39 mL) was added dropwise to the first solution. After two hours at -78 °C, the reaction was quenched by the slow addition of saturated ammonium chloride (50 mL) solution. The reaction mixture was then diluted with ethylacetate and the layers were separated. The organic layer dried over sodium sulfate and concentrated. Flash column chromatography carried out in 2:8 ethylacetate: hexanes afforded the product (6 g, 53%). NMR 5 ppm (CDCI3): 5.7 (m, 1H), 5.1 (dd, 2H), 4.4 (m, 1H), 2.6 (m, 2H), 2.4 (m, 1H), 1.8-2.2 (m, 1H), 1.45 (s, 9H), 1.4 (s, 9H). Step 2. Synthesis of N-Boc-Dvroalutamic(4.4-diallvlVtert-butvlester: N-Boc-pyroglutamic(4-allyl)-tert-butylester obtained in the Step 1 above (2.68 g, 8.24 mmol) was subjected to a second alkylation with allyl bromide under similar conditions. Flash chromatography in 15:85 ethylacetate: hexanes provided 2.13 g product (71%) as a clear oil. Step 3. Synthesis of Boc-Pro(4.4-dialMVtert-butvlester: Part a: To a cooled (-78 °C) solution of Boc-PyroGIu(4,4-diallyl)-tert-butylester (2.13 g, 5.83 mmol) in tetrahydrofuran (14 ml) was added lithium triethylborohydride (1M in tetrahydrofuran, 7.29 ml, 7.29 mmol) over five minutes. After two hours at -78 °C, the reaction was warmed-up to 0 °C and quenched by the slow addition of saturated sodium bicarbonate solution (20 ml) and 30% hydrogen peroxide (20 drops). Stirring continued for 20 minutes. The tetrahydrofuran was removed under reduced pressure and the remaining thick white residue was diluted with water (80 ml) and extracted three times with dichloromethane. The organic layer was dried, filtered and concentrated and taken to the next step without further purification. Part b): To the product obtained in part (a) in dichloromethane (14 ml) was added triethylsilane (931 jal, 5.83 mmol) followed by boron trifluoride diethyl etherate (776 jal, 6.12 mmol). After thirty minutes more triethylsilane (931 p.l, 5.83 mmol) and boron trifluoride diethyl etherate etherate (776 \x\, 6.12 mmol) were added and the reaction was stirred at -78 °C for three hours at which time the reaction was quenched by the slow addition of saturated sodium bicarbonate solution and water. The reaction mixture was extracted with dichloromethane and the organic layer was dried, filtered and concentrated. Flash column chromatography in 15% ethylacetate in hexanes afforded 1.07 colorless oil (57%). NMR 5 ppm.(CDCI3): 5.7-5.8 (m, 2H), 5.1 (m, 4H), 4.1-4.2 (2 dd's, 1H rotamers), 3.5-3.3 (dd, 1H) and 3.2 (dd, 1H) rotamers, 2.2-2.0 (m, 5H), 1.7(m, 1H), 1.46 (s, 9H), 1.43 (s, 9H). Step 4. Synthesis of Boc-Pro(4-spirocvclopenteneVtert-butvlester: To Boc-Pro(4,4-diallyl)-tert-butylester (1.07 g, 3.31 mmol) in dichloromethane (66 ml) was added 5% Bis(tricyclohexylphosphin)benzylidene ruthenium IV dichloride (Grubbs catalyst) and the mixture was heated at reflux for 1.5 hours. The reaction mixture was concentrated and the remaining residue was purified by flash column chromatography in 15% ethylacetate in hexanes. A yellow oil was obtained (0.57 g, 53%). NMR 5 ppm (CDCI3): 5.56 (bs, 2H), 4.2 and 4.1 (t, 1H, rotamers), 3.2-3.5 (m, 2H), 2.2-2.5 (m, 5H), 1.9 (dd, 1H) 1.47 and 1.46 (2 s's, 9H, rotamers), 1.45 and 1.44 (2 s's, 9H, rotamers). Step 5. Synthesis of Boc-Pro(4-sDirocvclooentane)-tert-butvlester: A solution of Boc-Pro(4-spirocyclopentene)-tert-butylester (1.12 g) in methanol (18 ml), water (4 ml) and acetic acid (4 ml) was placed in the Parr shaker and was hydrogenated for three hours at 35 psi in the presence of 10% palladium on carbon (300 mg). The catalyst was filtered off and the filtrate was concentrated to a colorless oil (1.26 g). NMR 8 ppm (CDCI3): 4.1 and 4.2 (t, 1H, rotamers, 3.4 (d, 1H), 3.2 (d, 1H), 2.1 (m, 1H), 1.9 (m, 1H), 1.6-1.7 (m, 10H), 1.5 (3 s's, 18H, rotamers). Step 6. Synthesis of Fmoc-Pro(4-spirocvclopentaneVcarboxvlic acid: The Boc-Pro(4-spirocyclopentane)-tert-butylester (1.26, 3.9 mmol) was treated with dichloromethane (10 ml) and trifluoroacetic acid (15 ml) for three hours. The reaction mixture was concentrated and the yellow oil obtained was dissolved in water (6 ml). Fluorenylmethyl succinyl carbonate (1.45 g, 4.3 mmol) dissolved in dioxane (6 ml) was added portionwise followed by the addition of potassium carbonate (2.16 g, 15.6 mmol). The reaction was stirred for 18 hours and concentrated. The remaining residue was diluted with the saturated sodium bicarbonate solution (10 mL) and washed with diethylether (3x10 ml). The aqueous layer was then acidified to pH ~ 1 with 1N sodium bisulfate solution and extracted with ethylacetate. The organic layer was dried over sodium sulfate, filtered and concentrated to a beige foam (1.3 g, 100%). Example VI. Synthesis of Boc-Prof4t-NH(Fmoc))-OH: Step 1. Synthesis of Na-tert-butoxvcarbonvl-cis-4-chloro-L-Droline benzyl ester: A mixture of the commercially available N-tert-butoxycarbonyl-trans-4-hydroxy-proline (8.79 g, 38 mmol), potassium carbonate (13.0 g, 94 mmol), benzyl bromide (4.5 ml, 38 mmol) and dimethylformamide (150 mL) was stirred for 18 h. Addition of ethyl acetate (100 mL) was followed by filtration. The white cloudy filtrate was clarified by the addition of 1M HCI (100 mL). The layers were separated and the aqueous layer was extracted with additional ethyl acetate (2 x 100 mL). The combined organic layers were washed with water (2 x 50 mL), dried (sodium sulfate), filtered and concentrated. Toluene was added to the crude benzyl ester, and the solution was filtered and reconcentrated. Dichloromethane (70 mL) and carbon tetrachloride (70 mL) was added, followed by triphenylphosphine (21.11 g, 80 mmol). The reaction mixture was stirred for 10 h, quenched with ethanol (7 mL) and stirred for 5 more h. The solution was concentrated to approx. 100 ml, then dichloromethane (40 mL) was added, followed by the addition of ether (200 mL) while stirring. The solution was cooled for 4 h, filtered and concentrated to give a yellow-brown oil which was purified by flash chromatography using ether/hexane/dichloromethane 2:2:1 to give the title compound (9.13 g, 26.9 mmol, 71%) as a white solid. Step 2. Synthesis of Na-tert-butoxvcarbonvl-trans-4-azido-L-proline benzyl ester: A solution of Na-tert-butoxycarbonyl-cis-4-chloro-L-proline benzyl ester (9.0 g, 26.5 mmol) and sodium azide (7.36 g, 113 mmol) in dimethylformamide (270 mL) was heated at 75°C for 2 days. Water (100 mL) was added and the reaction mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with water (3 x 50 mL), dried (sodium sulfate), filtered and concentrated. The oil was purified by flash chromatography using ethyl acetate/hexanes 1:1 to give the title compound (8.59 g, 24.8 mmol, 94%). Step 3. Synthesis of Boc-Pro(4t-NH(Fmoc))-OH: a A mixture of N-a-t-butoxycarbonyl-trans-4-azido-L-proline benzyl ester (8.59 g, 24.8 mmol) and 10% palladium on carbon (900 mg) in ethanol (500 mL) was hydrogenated at 50 psi for 14 h using a Parr hydrogenation apparatus. The mixture was filtered, concentrated, dissolved in methanol (60 mL), refiltered and concentrated to give a colorless oil. The oil was dissolved in water (53 mL) containing sodium carbonate (5.31 g, 50.1 mmol) and a solution of fluorenylmethyl succinyl carbonate (8.37 g, 29.8 mmol) in dioxane (60 mL) was added over 40 min. The reaction mixture was stirred at room temperature for 17 h, then concentrated to remove the dioxane and diluted with water (200 mL). The solution was washed with ether (3 x 100 mL). The pH of the aqueous solution was adjusted to 2 by the addition of citric acid (caution! foaming!) and water (100 mL). The mixture was extracted with dichloromethane (400 mL, 100 mL, 100 mL) and the combined organic layers were dried (sodium sulfate), filtered and concentrated to give the title compound. Example VII. Synthesis of N-t-butoxycarbonvl-4-trans-(N-fluorenvlmethvloxvcarbonviaminomethvlVL-Droline(Boc-Pro(4t-MeNHFmocVOHV Step 1. Synthesis tert-butoxvcarbonvl cis-4-hvdroxv-L-proline benzvl ester (Boc-Pro(4-cis-OHVOBn): To a mixture of cis-hydroxy-L-proline (5 g, 38.1 mmol) in benzene (45 ml_) and benzyl alcohol (45 mL) was added p-toluenesulfonic acid monohydrate (7.6 g, 40.0 mmol). The reaction mixture was heated at 125°C for 20 h while water (2ml) was removed using a Dean-Stark trap. The solution was filtered while still hot, and then ether (150 ml) was added. The solution was allowed to cool for three h at room temperature, then three h at 4 °C. The resulting solid was collected, washed with ether (100 mL) and dried in vacuo for 1 h to give 13.5 grams of white solid. The solid was dissolved in dioxane (40 mL) and diisopropylethylamine (7.6 mL), and then di-tert-butyl-dicarbonate (10 g, 45.8 mmol) was added over 5 min while using an ice bath to maintain a constant reaction temperature. After 10 h at room temperature the reaction mixture was poured into cold water (200 mL) and extracted with ethyl acetate (3 x 200 mL). The combined organic layers were washed with water (3 x 100 mL) and saturated aqueous sodium chloride (50 mL), dried (sodium sulfate), filtered and concentrated. The crude product was purified by flash chromatography using 40-60% ethyl acetate in hexanes to give the title compound (10.04 g, 31.24 mmol, 82%). Step 2. Synthesis of N-t-butoxvcarbonvl cis-4-mesvloxv-L-proline benzyl ester (Boc-Pro(4-cis-OMsVOBn): To a solution of Boc-Pro(4-cis-OH)-OBn (8.45 g, 26.3 mmol) in pyridine (65 mL) at 0°C, was added methanesulfonyl chloride (3.4 ml_, 44 mmol) dropwise over 7 min. The reaction mixture was allowed to warm to room temperature over 2 h, then stirred overnight. A solution of 10% water in pyridine (20 mL) was added oyer 15 min and the reaction mixture was concentrated. The residue was dissolved in water and extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with water (2 x 50 mL) saturated aqueous sodium bicarbonate (50 mL) and saturated aqueous sodium chloride (50 mL), dried (sodium sulfate), filtered and concentrated. The resulting residue was dissolved in toluene (100 mL) and concentrated to remove traces of pyridine. The residue was dried in vacuo for 30 min to afford the title compound (10.7 g, 102%), then used in the next step without purification. Step 3. N-t-butoxvcarbonvl-trans-4R-cvano-L-proline benzvlester (Boc-Pro(4-trans-CNVOBn): A solution of Boc-Pro(4-cis-OMs)-OBn (10.7 g, 26.3 mmol) and tetrabutylammonium cyanide (15.0 g, 56 mmoi) in dimethylformamide (100 mL) was heated in an oil bath at 55°C for 28 h. After cooling, water (150 mL) was added and the mixture was extracted with ethyl acetate (3 x 200 mL). The combined organic layers were washed with water (3 x 100 mL) and saturated aqueous sodium chloride (100 mL), dried (sodium sulfate), filtered and concentrated. The resulting residue was purified by flash chromatography (1:1 ether/hexanes) and then recrystallized from ethyl acetate/hexanes to provide the title compound (2.40 g, 7.26 mmol, 28%). • Step 4, N-t-butoxvcarbonvl-4-trans-(N-fluorenvlmethvloxvcarbonvl aminomethvIV L-proline (Boc-Pro(4t-MeNHFmocVOm: A mixture of the compound of Step 3 above (2.31 g, 7 mmol), water (10 mL), methanol (85 mL) and 10% palladium on carbon (700 mg) was hydrogenated at 50 psi for 11 h using a Parr hydrogenation apparatus. The mixture was filtered and concentrated. Water (15 mL) and sodium carbonate (1.5 g, 14.2 mmol) was added to the residue. A solution of fluorenylmethyl succinyl carbonate (2.36 g, 7.0 mmol) in dioxane (17 mL) was added over 5 min and stirring was continued for 28 h at room temperature. The reaction was concentrated in vacuo to a 15 mL volume, and water (100 mL) was added. The solution was washed with ether (3 x 75 mL). The pH of the aqueous solution was adjusted to 2 by the addition of citric acid (approx. 20 g, caution! foaming!) and water (100 mL). The mixture was extracted with dichloromethane (4 x 100 mL), and the combined organic layers were dried (sodium sulfate), filtered and concentrated. The crude product contained a major impurity which necessitated a three step purification. The crude product was dissolved in dichloromethane (50 mL) and trifluoroacetic acid (50 mL) and stirred for 5 h before being concentrated. The residue was purified by preparatory reverse-phase HPLC. The pure 4-(N-fluorenylmethyloxycarbonyl aminomethyl)proline trifluoroacetate salt (1.887 g, 3.93 mmol) was dissolved in dioxane (10 mL), acetonitrile (20 mL) and diisopropylethylamine (1.4 mL, 8 mmol). To the reaction mixture was added a solution of di-tert-butyldicarbonate (1.1g, 5 mmol) in dioxane (5 mL). After stirring for 18 h, the pH of the solution was adjusted to 2 by the addition of citric acid (caution: foaming!) and water (100 mL). The mixture was extracted with ethyl acetate (3 x 150 mL) and the combined organic layers were washed with saturated aqueous sodium chloride (100 mL), dried (sodium sulfate), filtered and concentrated. The crude product was dissolved in saturated aqueous sodium bicarbonate(100 mL) and washed with ether (3 x 75 mL). The aqueous layer was adjusted to pH = 3 by the addition of citric acid, then extracted with dichloromethane (4 x 100 mL). The combined organic layers were dried (sodium sulfate), filtered and concentrated to the title compound (1.373 g, 2.94 mmol, 42%). Example Vlli. Synthesis of 3.4-isooropvlideneprolinol: Step I. Cvclopropanation reaction (Tetrahedron Lett. 1993. 34(161. 2691 and 2695): To a stirring solution of isopropyltriphenyl- phosphonium iodide (4.14 g, 9.58 mmol) in tetrahydrofuran (60 ml_) at 0 °C, was added n-butyllithium (1.6 M in hexanes, 5.64 mL, 9.02 mmol) over 5 min. After 30 min, a solution of enamide ((5R, 7S)-5-phenyl-5,6,7,7a-tetrahydro-6-oxapyrrolizin-3-one) (1.206 grams, 6.0 mmol) (see J. Org. Chem. 1999, 64(2), 547 for the synthesis of the enamide starting material) in tetrahydrofuran (40 mL) was added over 10 min. After an additional 10 min, the cooling bath was removed and the reaction mixture was stirred at room temperature for 4 hours. The reaction was poured into water (400 mL) and extracted with diethyl ether (400 mL) and ethylacetate (2 x 400 mL). The . combined organic extracts were dried with sodium sulfate, filtered and concentrated to give the desired crude product. The residue was purified by flash chromatography eluting with 3:5:2 ethylacetate/hexanes/methylene chloride to give pure cyclopropanated product (750 mg, 3.08 mmol, 51%). Step 2. Synthesis of 3.4-isopropviideneprolinol Pr3.4-(diMe-cvcloproDvlY|-alcohol) (J. Ora. Chem. (1999) 64(2). 330): A mixture of the product obtained in step 1 above (1.23 grams, 5.06 mmol) and lithium aluminum hydride (1.0 M in THF, 15 mL, 15 mmol) was heated at reflux for 5 hours. After cooling to 0 °C, the remaining aluminum hydride was carefully quenched by the dropwise addition of saturated aqueous sodium sulfate (1.5 mL) over 15 min. The mixture was diluted with ethylacetate (40 mL) and then filtered through celite. The filtrate was dried with sodium sulfate, filtered and concentrated to give crude N-benzyl aminoalcohol (1.25 grams), which was carried on to the next step without further purification. A solution of crude N-benzyl aminoalcohol (1.25 grams, 5.06 mmol) in 1:1 acetic acid/ethylacetate (30 mL) with 10% Pd/C (1 gram) was hydrogenated at 50 psi for 16 hours using a Parr hydrogenation apparatus. The reaction mixture was filtered to remove the carbon-based catalyst and the filtrate was concentrated. The residue was dissolved in water (30 mL) and the pH was adjusted to 13 with 50% NaOH. The mixture was extracted with ether (3 x 60 mL). The combined extract was dried with sodium sulfate, filtered and concentrated to give crude aminoalcohol (485 mg, 3.43 mmol). This material was taken to the next step without further purification. Example IX. Synthesis of iBoc-G(ChxVPro(3.4-isopropvlideneV carboxvlic acid : To a solution of the commercially available cyclohexylglycine hydrochloride (15 g, 77.4 mmol) in acetonitrile (320 ml) and water (320 ml) was added potassium carbonate. Isobutylchloroformate (11.1 ml, 85.1 mmol) was added to the clear solution over 15 minutes and the reaction was stirred for 17 hours. The acetonitrile was removed under reduced pressure and the remaining aqueous layer was extracted twice with ether (100 ml). The aqueous layer was then acidified to pH 1 with 6N hydrochloric acid and extracted with dichloromethane (3 x 300 ml). The organic layer was dried over sodium sulfate, filtered and concentrated to yield 18.64 g (94%) product as a white solid. Step 2. Synthesis of isobutvloxvcarbonvl-cvclohexvlalvcvl-3.4-isoproDvlideneproline(iBoc-G(ChxVPf3.4-(diMe-cvcloDropvn]-OH^: a) Coupling step To a solution of iBoc-G(Chx)-OH (890 mg, 3.45 mmol) in acetonitrile (20 ml_) was added HATU (1.33 g, 3.5 mmol), HOAt (476 mg, 3.5 grams) and then diisopropylethylamine (2.5 mL, 14 mmol). After a 2 minutes, 3,4-isopropylideneprolinol (485 mg, 3.43 mmol) was added and the reaction mixture was stirred overnight. Addition of saturated aqueous sodium bicarbonate was followed by extraction with ether and ethylacetate. The combined organic layers were dried, filtered and concentrated. The residue was purified by flash chromatography eluting with 1:1 ethylacetate/hexanes to give pure dipeptide alcohol iBoc-G(Chx)-3,4-isopropylideneprolinol (870 mg, 2.3 mmol, 67%) b) Jones oxidation step To a solution of dipeptide alcohol iBoc-G(Chx)-3,4-isopropylideneprolinol (100 mg, 0.26 mmol) in acetone (2 mL) stirring at 0 °C was added Jones reagent (300 |iL) dropwise over 5 min. [Jones Reagent: Prepared from chromium trioxide (13.4 g) and concentrated sulfuric acid (11.5 mL) diluted with water to a total volume of 50 mL.] After stirring at 0 °C for 3 hours, isopropanol (500 ^L) was added and stirring continued for an additional 10 minutes. The reaction mixture was diluted with water (20 mL) and extracted with ethylacetate (3 x 70 mL). The combined organic layers were dried, filtered and concentrated to give the dipeptide iBoc-G(Chx)-3,4-isopropylideneproline (100 mg, 0.25 mmol, 96%). Example X. Synthesis of N-Cbz-3.4-methanooroline: Step 1. Synthesis of N-benzvl-3,4-methanoprolinol: A mixture of the benzylidene starting material (J. Org. Chem. 1999, 64(2), 547) (4.6 grams, 21.4 mmol) and lithium aluminum hydride (1.0 M in THFi 64 mL, 64 mmol) was heated at reflux for 5 hours. After cooling to 0 °C, the remaining aluminum hydride was carefully quenched by the dropwise addition of saturated aqueous sodium sulfate (5 mL) over 15 min. The mixture was diluted with ethylacetate (200 mL) and then filtered through celite. The filtrate was dried with sodium sulfate, filtered and concentrated to give crude N-benzyl aminoalcohol (3.45 grams), which was carried on to the next step without further purification. Step 2. Synthesis of N-benzvloxvcarbonvl-3,4-methanoprolinol (CBz-P(3,4-CH2V olV. A solution of crude N-benzyl aminoalcohol (3 grams, 14.76 mmol) in » methanol (120 mL) and concentrated HCI (1.5 mL) with 10% Pd/C (300 mg) was hydrogenated at 50 psi for 16 hours. The reaction mixture was filtered to remove the carbon-based catalyst and the filtrate was concentrated. The residue was dissolved in water/dioxane (100 mL) and diisopropylethylamine (3.2 mL) was added. Benzyl chloroformate (2.76 mL, 16.2 mmol) was added and the reaction was stirred overnight. The reaction mixture was concentrated, dissolved in 1M HCI (100 mL) and extracted with ethylacetate (3 x 200 mL). The combined organic layers were dried with magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography using 1:3 ethylacetate/hexanes to give the N-Cbz-3,4-methanoprolinol (2.4 g) Steo 3. Synthesis of N-benzvloxvcarbonvl-3.4-methanoproline (CBz-P(3,4-CH2V OHV. To a solution of N-Cbz-3,4-methanoprolinol (2.2 g, 8.90 mmol) in acetone (68 mL) stirring at 0 °C, was added Jones reagent (6.6 mL) dropwise over 5 min. [Jones Reagent: Prepared from chromium trioxide (13.4 g) and concentrated sulfuric acid (11.5 mL) diluted with water to a total volume of 50 mL.] After stirring at 0 °C for 3 hours, isopropanol (11 mL) was added and stirring continued for an additional 10 minutes. The reaction mixture was diluted with water (400 mL) and extracted with ethylacetate (3 x 500 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give N-Cbz-3,4-methanoproline (2.25 g, 96%) Example XI. Synthesis of Boc-(6S-carboethoxvmethano) proline: The synthesis of the title compound was carried out according to the published procedure: Marinozzi, M.; Nataini, B.; Ni, M.H.; Costantino, G.; Pellicciari R. IL Farmaco (1995; 50 (5), 327-331. Example XII. Synthesis of Boc-3-morpholine carboxvlic acid : The synthesis of the title compound was carried out according to the published procedure: Kogami Y., Okawa, K. Bull. Chem. Soc. Jpn. (1987) 60, 2963-2965. Example XIII. Synthesis of N-tert-butoxvcarbonvl 2-aza-3S-hvdroxvcarbonvl-f2.2.21-bicvclooctane: A solution of crude 2-aza-2-(1-phenylethyl)-3S-methoxycarbonyl-[2,2,2]-bicyclooct-5-ene (10 mmol) (Tetrahedron (1992) 48(44) 9707-9718) and 10% Pd on carbon (1 g) in methanol (30 mL) was acidified with 12N HCI then hydrogenated at 50 psi for 16 hours using a Parr hydrogenation apparatus. The reaction mixture was filtered to remove the carbon-based catalyst and the filtrate was concentrated. The residue was dissolved in concentrated HCI and stirred overnight. The solution was concentrated and redissolved in acetonitrile (50 ml_). Diisopropylethylamine (3.5 mL) and di-tert-butyldicarbonate (1 g) were added. The reaction mixture was stirred for 24 hours and then concentrated. The residue was dissolved in CH2CI2 and 5% aqueous sulfuric acid. The reaction mixture was extracted with CH2CI2 and the combined organic layers were concentrated. The residue was dissolved in 10% saturated sodium bicarbonate, washed with diethyl ether (2x) and acidified with 5% aqueous sulfuric acid. The aqueous layer was extracted with ethylacetate (2x). The combined ethylacetate layers were dried filtered and concentrated to give N-tert-butoxycarbonyl 2-aza-3S-hydroxycarbonyl-[2,2,2]-bicyclooctane (650 mg). Example XIV. Synthesis of isobuty(oxvcarbonvl-cvclohexvlqlvcvi-4.4-dimethyl proline (iBoc-G(ChxVP(4.4-dimethvlVOHV To a solution of iBoc-G(Chx)-OH (Example IX, Step 1.)(377 mg, 1.95 mmol) in acetonitrile (7 mL) was added successively HCl»HN-Pro(4,4-dimethyl)-l OMe (Example I, step 6)(377 mg, 1.95 mmol), N-hydroxybenzotriazole (239 mg, 1.75 mmol), TBTU (845 mg, 2.63 mmol) and diisopropylethylamine (1.35 mL, 7.8 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated and the remaining residue was dissolved in ethylacetate. The organic layer was washed twice with 10 mi portions of saturated sodium bicarbonate solution, 1N hydrochloric solution, and brine. The organic layer was dried over sodium sulfate, filtered and concentrated to a white solid (612 mg, 79%). Steo 2. Synthesis of iBoc-G(ChxVP(4.4-dimethvlVQH: The methyl ester obtained in Step 1 above (612 mg, 1.54 mmol) in methanol (6 ml) was saponified in the presence of 2M lithium hydroxide (1.16 ml) for three hours. The methanol was removed under reduced pressure and the remaining residue was diluted with ethylacetate and acidified to pH=2 with 1N hydrochloric acid. The layers were separated and the organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated. Example XV. Synthesis of L-phenylglycine dimethylamide Step 1. Synthesis of N-benzvloxvcabonvl -L-phenylqlvcine dimethvlamide (CBz-Pha-NMe2): N-benzyloxycarbonyl-L-phenylglycine (25g, 88 mmols) was dissolved in THF (800mL) and cooled to -10 °C. N-methylmorpholine (9.7 mL, 88 mmols) and isobutylchloroformate (11.4 mL, 88,0 mmols) were added and the mixture allowed . to stir for 1 minute. Dimethylamine (100 mL, 2M in THF) was added and the reaction was allowed to warm to room temperature. The mixture was filtered and the filtrate concentrated in vacuo to afford N-benzyloxycabonyl -L-phenylglycine dimethylamide (32.5 9) as a yellow oil. Step 2. Synthesis of L-phenvlalvcine dimethvlamide (H-Pha-NMe2): The N-benzyloxycarbonyl-L-phenylglycine dimethylamide (32.5 g) obtained above was dissolved in methanol (750 ml) and 10% palladium on activated carbon (3.3 g) was added. This mixture was hydrogenated on a Parr apparatus under 35 psi hydrogen for 2 hours. The reaction mixture was filtered and the solvent removed in vacuo and the residue recrystallized from methanol-hexanes to afford phenylglycine dimethylamide (26g) as an off white solid. The ee of this material was determined to be >99% by HPLC analysis of the 2,3,4,6-tetra-O-acetylglucopyranosylthioisocyanate derivative. Example XVI. Synthesis of (l-methvlcvclohexvl) glycine: Step 1.1-methyM-hydroxymethylcyclohexane To a solution of 1-methyl-1-hydroxycarbonylcyclohexane (10 g, 70 mmol) in tetrahydrofuran(300 raL) at 0 °C was added 1M diborane in tetrahydrofuran (200 mL, 200 mmol) over 90 minutes. The cooling bath was removed and the reaction mixture was stirred at room temperature for two days. The remaining borane was quenched by the slow addition of saturated sodium bisulfate (10 mL) over 90 min with cooling. Additional saturated sodium bisulfate (200 mL) was added and after 20 min of stirring the aqueous layer was removed. The organic layer was washed with water and saturated sodium chloride, dried, filtered and concentrated. The residue was purified by flash chromatography using 20% diethylether in hexanes to give 1-methyl-1-hydroxymethylcyclohexane (6.17 g, 48 mmol, 69%). Step 2.1-methvlcvctohexvlcarboxaldehvde: To a solution of 1-methyl-1-hydroxymethylcyclohexane (6.17 g, 48 mmol) and triethylamine (20.1 mL, 144 mmol) in dichloromethane (150 mL) at 0 °C, was added a solution of pyridine sulfur trioxide complex (22.9 g, 144 mmol) in dimethylsulfoxide (150 mL) over 15 min. The cooling bath was allowed to warm to room temperature over two hours, at which time the reaction mixture was poured into brine with ice (400 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (200 mL). The combined organic layers were diluted with hexanes (600 mL) and washed with 1M HCI (2 x 150 mL), saturated sodium chloride (2 x 100 mL), dried, filtered and concentrated. The residue was purified by flash chromatography to give 1-methylcyclohexylcarboxaldehyde (1.77 g, 13.8 mmol, 29%). Step 3. Synthesis of N-formvl-N-qlvcosvl- 1-methvlcvclohexvl- tert-butvlamide : The synthesis of the 2,3,4-tri-O-pivaloyl- - D-arabinosylamine was carried out according to the published procedure (Kunz. H.; Pfrengle, W.; Ruck, K.; Wilfried, S. Synthesis (1991) 1039-1042). To a solution of 1-methylcyclohexylcarboxaldehyde (1.17 g, 8.34 mmol), 2,3,4-tri-O-pivaloyl- -D-arabinosylamine (8.3 g, 20.7 mmol), formic acid (850 \xL, 22.2 mmol) and tert-butylisocyanide (2.4 mL, 21.2 mmol) in tetrahydrofuran (170 mL) at -30 °C was added 0.5M zinc chloride in tetrahydrofuran (41 mL, 20.57 mmol). The solution was stirred at -20 °C for 3 days, then concentrated. The residue was diluted with CH2CI2 (500 mL), washed with saturated sodium bicarbonate (2 x 500 mL), water (500 mL). The organic layer was dried, filtered and concentrated to give a clear oil. Flash chromatography (20% ethylacetate in hexanes) provided pure product (4.3 g, 6.6 mmol, 33%) Step 4. Synthesis of n-methvlcvclohexvOQlvcine: A solution of the product obtained in step 3 above (4.3 g, 6.6 mmoi) in dichloromethane (30 mL) and saturated anhydrous methanolic HCI (30 mL) was stirred overnight. The solution was concentrated and the residue was dissolved in water (100 mL) and washed with pentane (2 x 100 mL). The aqueous layer was concentrated and the residue was dissolved in 6N HCI (50-mL) and heated at reflux for 30 hours. The solution was concentrated to give the crude (1-methylcyclohexyl)glycine hydrochloride (790 mg, 3,82 mmoi, 58%). Example XVII. Synthesis of (4.4-dimethvlcvclohexvnqlvcine: Step 1. Synthesis of 4.4-dimethvlcvclohexanone: A mixture of 4,4-dimethylcyciohex-2-en-1-one (12 mL, 91.2 mmoi) and Degussa type 10% Pd on carbon (2 g) was hydrogenated at 40 psi for 18 hours. The mixture was filtered and concentrated (1H NMR showed a mixture of ketone and alcohol in a 5:3 ratio). The mixture was dissolved in acetone (400 mL) and cooled to 0 °C. Jones reagent (40 mL) was added over 30 min and the cooling bath was removed. After 2 days the excess acetone was evaporated and the resulting residue was dissolved in water and diethylether. The ether layer was washed with water until colorless, dried, filtered and concentrated to give 4,4-dimethylcyclohexanone (7.4 g, 58.6 mmol, 64%). Step 2. Synthesis of the methvl enol ether of 4.4-dimethvlcvclohexvlcarboxaldehvde: To a solution of methoxymethyl triphenylphosphonium chloride (8,6 g) in tetrahydrofuran (125 mL) at 0 °C was added n-butyllithium (1.6M in hexanes, 14.3 mL) over 10 min. After 30 min the reaction mixture was cooled to -78 °C and a solution of 4,4-dimethylcyclohexanone (2.45 g, 19.1 mmol) in tetrahydrofuran (50 mL) was added over 20 min. After 1 hour the cooling bath was remove and the reaction was warmed slowly to 0 °C. The reaction was diluted with saturated ammonium chloride (50 mL), ethylacetate (100 mL) and hexanes (100 mL), The organic layer was washed with water and brine, dried filtered and concentrated. The residue was stirred with hexanes (70 mL) for 10 min and filtered. The filtrate was concentrated and chromatographed using 25% ethylacetate in hexanes to give the title compound (1.925 g, 12.5 mmol, 65%). Step 3:4.4-dimethvlcvclohexvlcarboxaldehvde: A solution of the methyl enol ether of 4,4-dimethylcyclohexylcarboxaldehyde (1.925 g, 12.5 mmol) (Step II above), tetrahydrofuran (100 mL) and 6M HCI (20 mL) was stirred at room temperature for 4 hours. The reaction mixture was diluted with hexanes, diethylether, brine and water. The organic layer was dried, filtered and concentrated to give 4,4-dimethylcyclohexyicarboxaldehyde (1.0 g, 7.1 mmol, 57%). Step 4. Synthesis of N-formvl-N-qlvcosvl- 4,4-dimethvlcvclohexvl- tert-butvlamide : To a solution of 4,4-dimethylcyclohexylcarboxaldehyde (1.17 g, 8.34 mmol), 2,3,4-tri-O-pivaloyl-a-D-arabinosyiamine (3.43 g, 8.55 mmol), formic acid (350 nL, 9.17 mmol) and tert-butylisocyanide (990 nL, 8.76 mmol) in THF (70 mL) at -30 °C was added 0.5M zinc chloride in tetrahydrofuran (17 mL, 8.5 mmol). The solution was stirred at -20 °C for 2 days, then concentrated. The residue was diluted with dichloromethane (200 mL), washed with saturated sodium bicarbonate (2 x 200 mL), water (200 mL). The organic layer was dried, filtered and concentrated to give a clear oil. Flash chromatography (20% ethylacetate in hexanes) provided pure product (2.1 g, 3.3 mmol, 39%) Step 5. Synthesis of (4.4-dimethvlcvclohexvnqlvcine: A solution of the Ugi product obtained in step 4 above (2.1 g, 3.3 mmol) in dichioromethane (20 ml_) and saturated anhydrous methanolic HCI (20 mL) was stirred overnight. The solution was concentrated and the residue was dissolved in water (100 mL) and washed with pentane (2 x 100 mL). The aqueous layer was concentrated and the residue was dissolved in 6N HCI (40 mL) and heated at reflux for 30 hours. The solution was concentrated to give the crude (1-methylcyclohexyl)glycine hydrochloride (300 mg, 1.36 mmol, 41%). Example XVIII. Synthesis of Boc-nVal-rCHOHVGIv-OH: Step 1. Preparation of Boc-norvalinol: • To a solution of Boc-norvaline (25.0 g, 0.115 mol) in tetrahydrofuran (461 mL), cooled to 0°C, was added borane/tetrahydrofuran complex (461 mL of a 1.0M solution in tetrahydrofuran) dropwise. After 1h at 0°C, the solution was warmed to room temperature over a period of 1.5h. TLC indicated that the reaction was complete. Methanol was added to quench the reaction. The solution was concentrated to yield the title compound (22.56 g, 96%) as a foamy syrup. TLC of the products indicated satisfactory purity. Rf = 0.34 (40% ethyl acetate/hexanes). Step 2. Preparation Boc-norvalinal: To Boc-norvalinol (7.77 g, 38 mmol), in anhydrous dimethylsulfoxide (153 mL) and toluene (153 mL) was added EDC (73.32g, 382 mmol). After the solution was cooled to 0°C, dichloroacetic acid (15.8 mL, 191 mmol) was added dropwise. After addition was complete, the reaction was stirred for 15 min. The solution was allowed to warm to room temperature over a period of 2h. The reaction mixture was concentrated to remove the toluene, then dissolved in ethyl acetate. The solution was washed successively with 1N sodium bisulfate, saturated sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated to afford crude Boc-norvalinal which was used directly in the next step. TLC Rf = 0.84 (40% ethyl acetate/hexanes). Step 3. Synthesis of Boc-nVakCHOHVGlv-OEt: To a solution of the crude Boc-norvalinal (4.18 g, 20.77 mmol) in dichloromethane (83 mL) was added ethylisocyanoacetate (2.72 ml, 24.93 mmol) and pyridine (6.72 ml, 83.09 mmol). After the solution was cooled to 0°C, trifluoroacetic acid (4.15 ml, 41.54 mmol) was added dropwise. After stirring for 1h, the solution was stirred at room temperature for 18 hours while allowing the solvent from the reaction mixture in an uncovered vessel to evaporate under ambient conditions. The reaction mixture was concentrated, then dissolved in ethyl acetate. The solution was washed successively with 1N sodium bisulfate, saturated sodium bicarbonate and brine, dried over sodium sulfate, filtered and then concentrated. The residue was purified by flash chromatography eluting with 20% to 40% ethylacetate/hexanes to afford 2.8 g of the title compound as a yellow syrup. Low resolution mass spectroscopy confirmed the presence of the desired product (MH+ 333). Step 4. Synthesis of Boc-nVal-(CHOHVGIv-OH: The product obtained (Boc-nVai-(CHOH)-Gly-OEt) (1.52 g, 4.70 mmol) dissolved in ethanol (23 ml) was saponified with 1N lithium hydroxide (18.81 ml) for two hours at room temperature. The reaction mixture was acidified to pH = 2 with Dowex® 50 WX8 ion exchange resin, stirred for 20 minutes and then filtered. The resin was washed well with ethanol and water and the combined filtrates were concentrated to a white foam (0.48 g, 33%). Example XVIV. Synthesis of (2R.3S.4S.5SVtert-Butvl N-CBz-3-amino-2-hvdroxv-4.5 methylene-hexanoate: Step 1: To a solution of tert-Butyl diethylphosphonoacetate (4.7 ml_, 20 mmol) dissolved in THF (50 mL) at -78° C was added 1.6M n-butyl lithium in hexanes (12.4 mL). After 30 minutes (1S, 2S)-2-methylcyclopropylcarboxaldehyde (1 g, 12 mmol) (Barrett, A. G. M.; Doubleday, W. W.; Kasdorf, K.; Tustin, G. J., J. Org. Chem. (1996) 61, 3280) in diethyl ether (100 mL) was added over 10 min. The reaction was warmed to 0° C for 2 hours and to 6 °C for 12 hours. The reaction was quenched with saturated ammonium chloride (20 mL) and the organic layer was separated, washed with 50 mL brine and dried over sodium sulfate, filtered and concentrated to afford 3.5 g of a clear oil. Flash chromatography (20% ethylacetate in hexanes) afforded pure unsaturated tert-butylester (1.4 g). Step 2: To a solution of benzyl carbamate (3.55g, 23.5 mmols) in n-propanol (24 mL) was added a solution of sodium hydroxide (900 mg ,22.7 mmol)in water (48 mL), followed by tert-butylhypochlorite (2.57 mL, 22.7 mmol). After 15 minutes the reaction was cooled to 0 °C and (DHQ)2PHAL (350 mg, 0.45 mmoi) was added in n-propanol (24 mL), followed by unsaturated tert-butyl ester (1.4 g) from above in n-propanol (48 mL). Finally potassium osmate (110 mg, 0.30 mmol) in water (2 mL) was added and the solution very rapidly developed a dark green color which persisted for 4 hours. After 6 hours saturated sodium sulfate (50 mL) was added and the mixture extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with brine (30 mL), dried over sodium sulfate, filtered and concentrated. Flash chromatography with 20% ethylacetate in hexanes afforded the desired cBz protected amino tert-butylester as a white solid (3-16 mg). A mixture of CBz protected amino tert-butylester (316 mg, 0.9 mmoi) and 32mg 10% palladium on carbon in 9 mL methanol was hydrogenated for 8 hours. The mixture was filtered and concentrated to afford the free amine as a clear oil (195 mg). Example XX. Synthesis of 1R.2-dimethvlPropvl chloroformate: To the commercially available 2R-hydroxy-3-methylbutane (410 mg, 4.65 mmol) was added a solution of 20% phosgene in toluene (1 mL, 2 mmol). The solution was stirred for 6 hours to generate the chloroformate (2 mmol) which was reacted directly and immediately with the desired amine. The S-isomer was synthesized by the same procedure. II) Representative solution phase synthesis of HCV inhibitors Example XXI, Solution phase synthesis of iBoc-G(Chx)-Pro(4,4-dimethyl)-Leu-(CO)-Gly-Phg-dimethylamide: i Step 1. Synthesis of tert-butvloxvcarbonvl-leucinal (Boc-Leu-CHO): To a solution of the commercially available (Advanced Chem Tech) Boc-L-leucinol (0.78 g, 3.6 mmol) in anhydrous dichloromethane (17.5 ml) was added triethyl amine (2 ml, 14.36 mmol) and the mixture was cooled to 0 °C. Dimethyl sulfoxide (17.5 ml) was added followed by sulfur trioxide pyridine complex (2.3 g, 14.36 mmol) and the reaction was stirred for two hours. TLC in 1:1 ethylacetate: hexanes confirmed the completion of the reaction. The reaction mixture was concentrated and the remaining residue diluted with ethylacetate. The ethylacetate layer was washed with 1M hydrochloric acid (2x 75 ml) followed by saturated sodium bicarbonate solution (2 x 75 ml) and brine (75 ml). The organic layer was dried (sodium sulfate), filtered and concentrated to yield 775 mg of product. Step 2. Synthesis of Boc-2-hvdroxv-3-amino-5-methvl hexanovl-qlvcine ethvl ester (Boc-Leu-(CHOHVGIv-OEt): To a solution of Boc-Leucine aldehyde (0.77 g, 3.59 mmol) in anhydrous dichloromethane (24 ml) was added anhydrous pyridine (1.16 ml, 14.36 mmol) and ethylisocyanoacetate (0.4 ml, 4.66 mmol). The reaction mixture was cooled to 0 °C and trifluoroacetic acid (0.55 ml, 7/18 mmol) was added over two minutes. The reaction mixture was capped and stirred at 4 °C for four days, and at room temperature for one day. The reaction mixture was diluted with dichloromethane (350 ml) and washed twice each with 75 ml portions of 1M hydrochloric acid, saturated sodium bicarbonate and brine. The organic layer was dried, filtered and concentrated. The residue obtained was subjected to flash chromatography in a 2" x 6" silica ge! column using 10% ethyiacetate in hexanes (800 ml) followed by 1:1 ethyiacetate in hexanes (800 ml). The fractions corresponding to the product were pooled and concentrated to yield 980 mg (79%) product. Step 3. Synthesis of Boc-Leu-(CHOHVGIv-OH: To a solution of Boc-Leu-(CHOH)-Gly-Oet (0.98 g, 2.83 mmoi) in ethanol (11.3 ml) was added 2M lithium hydroxide (4.25 ml) and the reaction was stirred for five hours at room temperature. The ethanol was removed under reduced pressure and the aqueous layer was diluted with ethyiacetate. The organic layer was washed with 1M hydrochloric acid followed by brine, dried, filtered and concentrated to yield 775 mg (86%) product as a white solid. a Step 4. Synthesis of Boc-Leu-(CHOHVGIv-Pha-dimethvlamide: To a solution of Boc-l_eu-(CHOH)-Gly-OH (0.37 g, 1.18 mmol) in acetonitrile (23 ml) was added successively phenylglycine dimethylamide (obtained in Example XV, Step 2), EDC (0.34 g, 1.76 mmol), N-hydroxybenzotriazole (HOBt)(0.18 g, 1.18 mmol) and diisopropylethylamine (DIEA) (0.82 ml, 4.7 mmol) and the reaction was stirred for 18 hours at room temperature. The reaction mixture was concentrated and the remaining residue was diluted with ethyiacetate and washed successively with two 75 ml portions of 1M hydrochloric acid, saturated sodium bicarbonate and brine. The organic layer was then dried filtered and concentrated. The crude product was subjected to flash chromatography in a 2" x 6" silica gel column using 4:1 ethylacetate: hexanes (700 ml) followed by ethylacetate (1000 ml) and 10% methanol in dichloromethane (600 ml). The fractions corresponding to the product were pooled and concentrated to yield 445 mg (80%) white solid. Step 5. Synthesis of H-Leu-(CHOH)-Glv-Pha-dimethvlamide trifluoroacetate salt: To a solution Boc-Leu-(CHOH>Gly-Phg-dimethylamide (70 mg, 0.146 mmol) in dichloromethane (1 ml) was added trifluoroacetic acid (1 ml) and the reaction was stirred at room temperature for 1 hour. The reaction mixture was concentrated and taken to the next step without further purification. Step 6. Synthesis of iBoc-G(ChxVPro(4.4-dimethvlVLeu-(CHOHVGIv-Pha- dimethvlamide: i i To a solution of iBoc-G(Chx)-P(4,4-diMe)-OH (Example XIV, step 2)(53 mg, 0.148 mmol) in acetonitrile (3 ml) was added successively TFA*2HN-I_eu(CHOH)-Gly-Phg-NMe2 (61 mg, 0.148 mmol), N-Hydroxybenzotriazole (HOBt) (23 mg, 0.148 mmol), TBTU (71.5 mg, 0.222 mmol and diisopropylethyl amine (103 I, 0.593 mmol). The reaction was stirred at room temperature for 18 hours and concentrated. The remaining residue was dissolved in ethylacetate and washed with 1M hydrochloric acid (2x5 ml), saturated sodium bicarbonate solution (2x5 ml), and brine (2x5 ml). The organic layer was dried, filtered and concentrated. The product (100 mg) was taken to the next step without further purification. Step 7. Synthesis of iBoc-G(ChxVPro(4.4-dimethvn-Leu-(COVGIv-Pha-dimethylamide: ■ To a solution of iBoc-G(Chx)-Pro(4,4-dimethyl)-Leu-(CHOH)-Gly-Phg-dimethylamide (30 mg, 0.04 mmol) in dichloromethane (1 ml) was added the commercially available Dess-Martin reagent (Omega Chemical Company lnc.)(67.8 mg, 0.16 mmol) and the reaction was stirred at room temperature for 90 minutes. The reaction mixture was concentrated and the remaining residue was stirred in 5% .sodium thiosulfate. It was then diluted with dichloromethane and the layers were separated. The organic layer was washed with sodium thiosulfate (4 x 3 ml), followed by water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was dissolved in hexanes and isopropyl alcohol and was subjected to HPLC purification using a normal phase Kromasil 5 silica column (Phenomenex, 250 x 21.20 mm, 100 angstrom pore size, 5 jam gel particles) eluting with a 30 minutes gradient consisting of 0 to 25% isopropyl alcohol in hexanes (25 ml/minutes). The fractions corresponding to the product were pooled and concentrated. Lyophilization from water yielded 6.7 mg white powder. Low resolution mass spectra confirmed the desired mass (MH+ = 741.4). IIH Solid Phase Synthesis: Solid-phase synthesis is useful for the production of small amounts of certain compounds of the present invention. As with the conventional solid-phase synthesis of peptides, reactors for the solid-phase synthesis of peptidyl ketoamides are comprised of a reactor vessel with at least one surface permeable to solvent and dissolved reagents, but not permeable to synthesis resin of the selected mesh size. Such reactors include glass solid phase reaction vessels with a sintered glass frit, polypropylene tubes or columns with frits, or reactor Kans^M made by Irori Inc., San Diego CA. The type of reactor chosen depends on volume of solid-phase resin needed, and different reactor types might be used at different stages of a synthesis. The following procedures will be referenced in the subsequent examples: Procedure A: Coupling reaction: To the resin suspended in N-methylpyrrolidine (NMP) (10-15 mL/ gram resin) was added Fmoc-amino acid (2 eq), HOAt (2 eq), HATU (2 eq) and diisopropylethylamine (4 eq). The mixture was let to react for 4-48 hours. The reactants were drained and the resin was washed successively with dimethylformamide, dichloromethane, methanol, dichloromethane and diethylether (use 10-15 mL solvent/ gram resin). The resin was then dried in vacuo. Procedure B: Fmoc deprotection: The Fmoc-protected resin was treated with 20% piperidine in dimethylformamide (10 mL reagent/ g resin) for 30 minutes. The reagents were drained and the resin was washed successively with dimethylformamide, dichloromethane, methanol, dichloromethane and diethyl ether (10 mL solvent/ gram resin). Procedure C: Boc deprotection: The Boc-protected resin was treated with a 1:1 mixture of dichloromethane and trifluoroacetic acid for 20-60 minutes (10 mL solvent/ gram resin). The reagents were drained and the resin was washed successively with dichloromethane, dimethylformamide, 5% diisopropylethylamine in dimethylformamide, dimethylformamide, dichloromethane and dimethylformamide (10 mL solvent/ gram resin). Procedure D: Semicarbazone hydrolysis: The resin was suspended in the cleavage cocktail (10 mL/ g resin) consisting of trifluoroacetic acid: pyruvic acid: dichloromethane: water 9:2:2:1 for 2 hours. The reactants were c rained and the procedure was repeated three more times. The resin was washed successively with dichloromethane, water and dichloromethane and dried under vacuum. Procedure E: HF cleavage: The dried peptide-nVal(CO)-G-0-PAM resin (50 mg) was placed in an HF vessel containing a small stir bar. Anisole (10% of total volume) was added as a scavenger. In the presence of glutamic acid and cysteine amino acids, thioanisole (10%) and 1,2-ethanedithiol (0.2%) were also added. The HF vessel was then hooked up to the HF apparatus (Immuno Dynamics) and the system was flushed with nitrogen for five minutes. It was then cooled down to -70°C with a dry ice/ isopropanol bath. After 20 minutes, HF was distilled to the desired volume (10 mL HF/ g resin). The reaction was let to proceed for one and a half hour at 0°C. Work up consisted of removing all the HF using nitrogen. Dichloromethane was then added to the resin and the mixture was stirred for five minutes. This was followed by the addition of 20% acetic acid in water (4 mL). After stirring for 20 minutes, the resin was filtered using a fritted funnel and the dichloromethane was removed under reduced pressure. The remaining residue and the mixture was washed with hexanes (2x) to remove scavengers. Meanwhile, the resin was soaked in 1 mL methanol. The aqueous layer (20% HOAc) was added back to the resin and the mixture was agitated for five minutes and then filtered. The methanol was removed under reduced pressure and the aqueous layer was lyophilized. The peptide was then dissolved in 10-25% methanol (containing 0.1% trifluoroacetic acid) and purified by reverse phase HPLC. Example XXII: Representative solid phase Synthesis of Hep C inhibitors: CiBoc-G(Chx)-Pr4t-NHS02PhVnV-(C0)-G-GfPh)-NH2) Step 1. Synthesis of Fmoc-nV-(dpscVGIv-OH: A) Synthesis of allvl isocvanoacetate (steps a-b below): a) Synthesis of isocyanoacetic acid potassium salt: Ethyl isocyanoacetate (96.6 ml, 0.88 mol) was added dropwise to a chilled solution of ethanol (1.5 L) and potassium hydroxide (59.52 g( 1.0 mol). The reaction was slowly warmed to room temperature. After two hours the precipitated product was filtered on a glass funnel and washed with several portions of chilled ethanol. The potassium salt of isocyanoacetic acid thus obtained was dried in vacuo to a golden-brown solid (99.92 g, 91.8%). b) Synthesis of allyl isocyanoacetate: To the product of part a (99.92 g, 0.81 mol) dissolved in acetonitrile (810 ml) was added allyl bromide (92 ml, 1.05 mol). After heating at reflux for four hours a dark brown solution was obtained. The reaction mixture was concentrated and the remaining residue was dissolved in ether (1.5 L) and washed three times with water (500 ml). The organic layer was dried, filtered and concentrated to a dark brown syrup. The crude was purified by vacuum distillation at 7 mm Hg (98 C) to a clear oil (78.92 g, 78%). NMR 5 ppm (CDCI3): 5.9 (m, 1 H), 5.3 (m, 2H), 4.7 (d, 2H), 4.25 (s, 2H). B) Synthesis of 9-fluorenvlmethoxvcarbonvl~norvalinal (steps a-c below): a) Synthesis of 9-fluorenylmethoxycarbonyl-L-norvaline methyl ester (Fmoc-nVal-OMe): To a chilled solution of the commercially available Fmoc-norvaline (25 g, 73.75 mmol) in anhydrous methanol (469 ml) was added thionyl chloride (53.76 ml, 737.5 mmol) over one hour. TLC in ethylacetate taken an hour later confirmed the completion of the reaction (Rf = 0.85). The reaction mixture was concentrated and the remaining residue was dissolved in ethylacetate. The organic layer was washed with several 200 ml portions of saturated sodium bicarbonate followed by brine. The organic layer was dried, filtered and concentrated to afford Fmoc-norVal-OMe) as a white solid (26.03 g) in quantitative yield. NMR 5 ppm (CD3OD): 7.7 (m, 2H), 7.6 (m, 2H), 7.4 (m, 2H), 7.3 (m, 2H), 4.3 (m, 2H), 4.1 (m, 2H), 3.7 (s, 3H), 1.7 (m, 1H), 1.6 (m, 1H), 1.4 (m, 2H), 0.95 (t, 3H). b) Synthesis of 9-fluorenylmethoxycarbonyl-norvalinol (Fmoc-nValinol): To Fmoc-nVal-OMe (26.03 g, 73.75 mmol) in tetrahydrofuran (123 ml) and methanol (246 ml) was added calcium chloride (16.37 g, 147.49 mmol). The reaction mixture was cooled to 0°C and sodium borohydride (11.16 g, 294.98 mmol) was added in several batches. To the thick paste obtained, methanol (500 ml) was added and the reaction was let to stir at room temperature for 90 minutes. TLC in 2:3 ethylacetate: hexanes confirmed the completion of the reaction (Rf = 0.25). The reaction was quenched with the slow addition of water (100 ml) at 0°C. The methanol was removed under reduced pressure and the remaining aqueous phase was diluted with ethylacetate. The organic layer was washed with water (3 x 500 mi), saturated sodium bicarbonate (3 x 500 ml) and brine (500 ml). The organic layer was dried over sodium sulfate, filtered and concentrated to a white solid (21.70 g, 90.5%). NMR 8 ppm (CD3OD): 7.8 (m, 2H), 7.7 (m, 2H), 7.4 (m, 2H), 7.3 (m, 2H), 4.3-4.5 (m, 2H), 4.2 (m, 1H), 3.6 (s, 1H), 3.5 (s, 2H), 1.5 (m, 1H), 1.3-1.4 (m,3H), 0.99 (m, 3H). c) Synthesis of 9-fluorenylmethoxycarbonyl-norvalinal (Fmoc-nVal-CHO): To a solution of Fmoc-norValinol (21.70 g, 66.77 mmol) in dichloromethane (668 ml) was added triethylamine (37.23 ml, 267 mmol) and the solution was cooled to 0°C. A suspension of pyridine sulfur trioxide complex (42.51 g, 267 mmol) in dimethylsulfoxide (96 ml) was added to the chilled solution. After one hour, TLC in 2:3 ethylacetate: hexanes confirmed the completion of the reaction. The dichloromethane was removed under reduced pressure and the remaining residue was dissolved in ethylacetate and washed with water (2 x 50 ml), 1N saturated sodium bisulfate (2 x 50 ml), saturated sodium bicarbonate (2 x 50 mi) and brine (50 ml). The organic layer was concentrated to yield a white solid. Theoretical yield (21.57 g) was assumed and the reaction was taken to the next step without further purification. C) Synthesis of diphenvlmethvl semicarbazide fdpsc) trifluoroacetate salt (steps a-b below): a) Synthesis of Boc-semicarbazid-4-yl diphenylmethane To a solution of carbonyldiimidazole (16.2 g, 0.10 mole) in dimethylformamide (225 ml) was added a solution of t-butyl carbazate (13.2 g, 0.100 mol) in dimethylformamide (225 ml) dropwise over 30 minutes. Diphenylmethylamine (18.3 g, 0.10 mol) was added next over 30 minutes. The reaction was allowed to stir at room temperature for one hour. Water (10 mL) was added and the mixture was concentrated to about 150 mL under reduced pressure. This solution was poured into water (500 mL) and extracted with ethyl acetate (400 mL). The ethylacetate phase was washed two times each with 75 mL 1N HCI, water, saturated sodium bicarbonate solution and sodium chloride, and dried with magnesium sulfate. The mixture was filtered and the solution was concentrated to give 29.5 g (85% yield) of a white foam. This material could be purified by recrystallization from ethyl acetate/hexane, but was pure enough to use directly in the next step: mp 142^143°C. ^H NMR (CDCI3) d 1.45 (s, 9H), 6.10 (dd, 2H), 6.42 (s, 1H), 6.67 (bs, 1H), 7.21-7.31 (m, 10H). Anal calculated for C19H23N3O3: C, 66.84; H, 6.79; N, 12.31. Found: C, 66.46; H, 6.75; N; 12.90. b) Synthesis of diphenylmethyl semicarbazide (dpsc) trifluoroacetate salt A solution of Boc-semicarbazid-4-yl diphenylmethane (3.43 g, 10 mmol) in dichloromethane (12.5 mL) was treated with 12.5 mL of trifluoroacetic acid at room temperature and stirred for 30 min. The solution was added dropwise to 75 mL of ether and the resulting solid (2.7 g, 80%) was collected by filtration, mp 182- 184°C. 1H NMR (CD3OD) d 6.05 (s, 1H), 7.21-7.35 (m, 10H). ™C NMR (CD30D)d 57.6, 118.3 (q, CF3), 126.7, 127.9, 141.6, 156.9, 160.9 (q, CF3CO2H). D) Synthesis of Fmoc-nVal-(CHOHVGIv-Oallvl: To a solution of Fmoc-nVal-CHO (Step IB) (5.47 g, 16.90 mmol) in dichloromethane (170 ml) was added allyl isocyanoacetate (Step I A) (2.46 ml, 20.28 mmol) and pyridine (5.47 ml, 67.61 mmol). The reaction mixture was cooled to 0°C and trifluoroacetic acid (3.38 ml, 33.80 mmol) was added dropwise. The reaction was stirred at 0°C for 1h, and then at room temperature for 48 hours. TLC taken in ethylacetate confirmed the completion of the reaction. The reaction mixture was concentrated and subjected to flash chromatography using 20% to 70% ethylacetate in hexanes. Fractions containing the desired product were pooled and concentrated to a white foam (6.88 g, 87.3%). TLC in 50:50 ethylacetate shows one spot (Rf = 0.37). NMR 8 ppm (CD3OD): 7.8 (m, 2H), 7.65 (m, 2H), 7.4 (m, 2H), 7.3 (m, 2H), 5.9 (m, 1H), 5.1-5.4 (m, 2H), 4.55-4.65 (m, 2H), 4.3-4.4 (m, 2H), 4.15-4.25 (m, 1H), 4.01 (s, 1H), 3.9-4.0 (m, 3H), 1.S-1.6 tm, zri), 1.35-1.45 (m,3H), 0.9 (m,3H). E) Synthesis of Fmoc-nVal-(COVGlv-Oallvl: to a solution of Fmoc-nVal-(CHOH)-Gly-Oallyl (Step D) (5.01 g, 10.77 mmol) in dimethylsulfoxide (100 ml) and toluene (100 ml) was added EDC (20.6 g, 107.7 mmol). The reaction mixture was cooled to 0 °C and dichloroacetic acid (4.44 ml, 53.83 mmol) was added dropwise. The reaction was stirred for 15 minutes at 0 °C and 1 h at room temperature. After cooling back to 0 C, water (70 ml) was added and the toluene was removed under reduced pressure. The remaining residue was diluted with ethylacetate and washed several times with a saturated sodium bicarbonate solution followed by 1N sodium bisulfate and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The theoretical yield of 4.99 g was assumed and the reaction was taken to the next step without further purification. TLC in 50:50 ethylacetate shows one spot (Rf = 0.73). Ft Synthesis of Fmoc-nVal-(dDScVGIv-OaHvl: To a solution of Fmoc-nVal-(CO)-Gly-Oallyl (Step E) (4.99 g, 10.75 mmol) in ethanol (130 ml) and water (42 ml) was added diphenylmethyl semicarbazide (dpsc) trifluoroacetate salt (Step IC) (7.6 g, 21.5 mmol) and sodium acetate •3H2O (1.76 g, 12.9 mmol), successively . The reaction mixture was heated at reflux for 90 minutes. The completion of reaction was confirmed by TLC taken in 1:1 ethylacetate: hexane. Ethanol was removed under reduced pressure and the remaining residue was dissolved in ethylacetate and washed with 1N sodium bisulfate (2x10 ml), saturated sodium bicarbonate (2x10 ml), followed by brine (10 mi). The organic layer was dried, filtered and concentrated. The resulting residue was purified by flash chromatography in 20% to 50% ethylacetate in hexanes to give a white solid (5.76g, 78%). TLC in 50:50 ethylacetate: hexanes showed two spots (cis and trans isomers) with Rf = 0.42 and 0.5. G) Synthesis of Fmoc-nVal-(dDscVGIv-OH: To a solution of Fmoc-nVal-(dpsc)-Gly-Oallyl (Step IG) (4.53 g, 6.59 mmol) in tetrahydrofuran (300 ml) was added dimedone (4.62 g, 32.97 mmol) followed by tetrakis(triphenylphosphine) palladium(O) catalyst (0.76 g, 0.66 mmol). The completion of the reaction was confirmed by TLC after 90 minutes using 9:1 dichloromethane: methanol. The reaction mixture was concentrated and the remaining residue was dissolved in ethylacetate and washed three times with 50 ml portions of 0.1 M potassium biphosphate. The organic layer was then treated with 50 ml sodium bisulfite and the two phase system was stirred for 15 minutes. The phases were separated and the procedure was repeated twice more. The organic layer was dried and concentrated and subjected to flash chromatography with 20% to 100% ethylacetate in hexanes. This was followed with 9:1 dichloromethane: methanol solution. The fractions corresponding to the pure product were pooled and concentrated to obtain a white solid (3.99 g, 94%). TLC n 9:1 dichloromethane: methanol showed two spots (cis and trans isomers). NMR 5 ppm (CD3OD): 7.75 (m, 2H), 7.6 (m, 3H), 7.2-7.4 (m, 14H), 6.1-6.2 (m, 1H), 4.25-4.4 (m, 2H), 4.1-4.2 (m, 2H), 3.85 (s, 2H), 1.6-1.8 (m, 2H), 1.3-1.5 (m, 2H), 0.95 (t, 3H). Step 2. Synthesis H-Pha-MBHA resin: The commercially available MBHA resin (2.6 g, 1.12 mmol/g, 2.91 mmol) was transferred to a 250 mL fritted solid phase reaction vessel equipped with a nitrogen inlet. It was then washed thoroughly with 30 ml portions of dichloromethane, methanol, dimethylformamide and dichloromethane and coupled over 18 hours to the commercially available Fmoc-Phg-OH (2.17 g, 5.82 mmol) according Procedure A with 99.82% efficiency. The resin was then subjected to Fmoc deprotection according to procedure B. A qualitative ninhydrin assay on a small aliquot gave dark blue resin and solution, indicating a successful reaction. Step 3. Synthesis of H-nValfdDscVGIv-Pha-MBHA resin: The resin obtained in step II (2.6 g, 0.8 mmol/g, 2.91 mmol) was reacted with Fmoc-nVal-(dpsc)-Gly-Oallyl (Step IG) (5.82 mmol, 3.77 g) according to Procedure A. After 18 hours, quantitative ninhydrin analysis indicated 99.91% coupling efficiency. The resin was subjected to Fmoc deprotection according to procedure B. A qualitative ninhydrin assay on a small aliquot gave dark blue resin and solution, indicating a successful reaction. Step 4. Synthesis of Boc-Pro(4t-NHFmocVnVal(dDscVGIv-Pha-MBHA resin: ^NH-Fmoc Boc-hl) I 0^N\/^N/N|(/NV^NH-MBHA resin j» 6 NH-CH(Ph)2 0^N-aY^N^YN^^NH^MBHA resin ]•> 6 NH-CH(Ph)2 The compound H-nVal(dpsc)-Gly-Phg-MBHA resin (Step 3 above) (600 mg, 0.8 mmol/g, 0.67 mmol) was transferred to a fritted polypropylene tube and was coupled to Boc-Pro(4t-NHFmoc)-OH (Example VI, Step 3) (610 mg, 1.34 mmol) according to procedure A. After 18 hours, quantitative ninhydrin analysis indicated 99.96% coupling efficiency. Step 5. Synthesis of Boc-Pro^t-NH^-nVaKdpscVGIv-PhQ-MBHA resin: The resin from the previous step (Boc-Pro(4t-NHFmoc)-nVal(dpsc)-Gly-Phg-MBHA resin) was subjected to Fmoc deprotection according to procedure B. A qualitative ninhydrin assay on a small aliquot gave dark blue resin and solution, indicating a successful reaction. Step 6. Synthesis of Boc-Pro(4t-NHS02BnVnVal(dPscVGIv-Pha-MBHA resin: To the resin obtained from the previous step (Boc-Pro(4t-NH2)-nVal(dpsc)-Gly-Phg-MBHA resin) (0.2 g, 0.22 mmol) suspended in NMP (2 ml) was added 2,4,6-collidine (0.24 ml, 1.79 mmol) and benzenesulfonyl chloride and the reaction was shaken for 18 hours. The solvent was drained and the resin was washed thoroughly with 2 ml portions of dichloromethane, methanol, dimethylformamide and dichloromethane. Qualitative ninhydrin analysis showed colorless beads and solution indicating a successful reaction. Step 7. Synthesis of Fmoc-G(ChxVPro(4t-NHSOoBnVnVal(dpscVGIv-Pha-MBHA resin: The resin obtained in the previous step (Boc-Pro(4t-NHS02Bn)-nVal(dpsc)-Gly-Phg-MBHA resin) was subjected to the Boc deprotection procedure according to Procedure C. Fmoc-G(Chx) (0.17 g, 0.45 mmol) was then coupled according to procedure A. After 18 hours qualitative ninhydrin analysis showed colorless beads and the quantitative ninhydrin analysis indicated 99.79% coupling efficiency. Step 8. Synthesis of iBoc-G(ChxVPro(4t-NHSQ2BnVnVal(dDscVGIv-Pha-MBHA resin: The resin obtained in the previous step (Fmoc-G(Chx)-Pro(4t-NHS02Bn)-nVal(dpsc)-Gly-Phg-MBHA resin) was subjected to Fmoc deprotection according to procedure B. A ninhydrin assay on a small aliquot gave dark blue resin and solution, indicating a successful reaction. To the resin (0.2 g, 0.22 mmol) suspended in 2 ml NMP was added isobutylchloroformate (0.12 ml, 0.90 mmol) followed by diisopropylethylamine (0.31 ml, 1.79 mmol), and the reaction mixture was shaken for 18 hours at room temperature. Qualitative ninhydrin analysis showed colorless beads and solution indicating a successful reaction. Step 9. Synthesis of iBoo-GrChxVProf4t-NHSQ2BnVnValfCOVGIv-Phg-MBHA resin: The compound of the previous step (iBoc-G(Chx)-Pro(4t-NHS02Bn)-nVaI(dpsc)-Gly-Phg-MBHA resin) (200 mg) was subjected to semicarbazone hydrolysis Procedure D. Step 10. Synthesis of Synthesis of iBoc-G(ChxVPro(4t-NHSQ2BnVnVal(COVGIv-Pha-NH2: The resin of the previous step (iBoc-G(Chx)-Pro(4t-NHS02Bn)-nVal(CO)-Gly-Phg-MBHA resin) (100 mg) was subjected to HF cleavage condition (Procedure E) to yield the desired crude product. The material was purified by HPLC using a 2.2 x 25 cm reverse phase column, containing a C-18 resin comprised of 10 micron size gel particles with a 300 angstrom pore size, eluting with a gradient using 20-50% acetonitrile in water. Analytical HPLC using a 4.6 x 250 mm reverse phase column, containing a C-18 resin comprised of 5 micron size gel particles with a 300 angstrom pore size, eluting with 25-75% acetonitrile (containing 0.1% trifluoroacetic acid) showed one peak at 13.5 minutes. Low resolution mass spectrum confirmed the desired mass (MH+ 826.4). IV. Additional Compounds Prepared bv Solution Phase Synthesis: Representative procedures to prepare additional inventive compounds are shown below, and the compounds prepared by such procedures are listed in Table 5, Example XXIII: Preparation of a Compound of Formula XXIH: A stirred solution of ketimime XXIIla (50 g, 187.1 mmol) under N2 in dry THF (400 mL) was cooled to -78 °C and treated with 1 M solution of K^BuO (220 mL, 1.15 equiv.) in THF. The reaction mixture was warmed to 0 °C and stirred for 1 h and treated with bromomethyi cyclobutane (28 mL, 249 mmol). The reaction mixture was stirred at room temperature for 48 h and concentrated in vacuo. The residue was dissolved in Et20 (300 mL) and treated with aq. HCl (2 M, 300 mL) The resulting solution was stirred at room temperature for 5 h and extracted with Et20 (1 L). The aqueous layer was made basic to pH -12-14 with NaOH (50 % aq.) and extracted with CH2CI2 (3x300 mL). The combined organic layers were dried (MgS04), filtered, and concentrated to give pure amine (XXHIb, 18 g) as a colorless oil. Step 2. A-solution of amine XXHIb (18g, 105.2 mmol) at 0 °C in CH2CI2 (350 mL) was treated with di-terf-butyldicarbonate (23 g, 105.4 mmol) and stirred at rt. for 12 h. After the completion of the reaction (TLC), the reaction mixture was concentrated in vacuo and the residue was dissolved in THF/H2O (200 ml, 1:1) and treated with LiOH*H20 (6.5 g, 158.5 mmol) and stirred at room temperature for 3 h. The reaction mixture was concentrated and the basic aqueous layer was extracted with Et20. The aqueous layer was acidified with cone. HCl to phM-2 and extracted with CH2CI2. The combined organic layers were dried (MgS04), filtered, and concentrated in vacuo to yield XXIlIc as a colorless viscous oil which was used for next step without any further purification. Step 3. A solution of acid XXIIIc (15.0 g, 62 mmol) in CH2CI2 (250 mL) was treated with BOP reagent (41.1 g, 93 mmol), N-methyl morpholine (27 mL), N,0-dimethyl hydroxylamine hydrochloride (9.07 g, 93 mmol) and stirred overnight at it The reaction mixture was diluted with 1 N aq. HCI (250 mL), and the layers were separated and the aqueous layer was extracted with CH2CI2 (3x300 ml). The combined organic layers were dried (MgS04), filtered and concentrated in vacuo and purified by chromatography (Si02, EtOAc/Hex 2:3) to yield the amide XXIIId (15.0 g) as a colorless solid. Step 4. A solution of amide XXIIId (15 g, 52.1 mmol) in dry THF (200 mL) was treated dropwisely with a solution of LiAIH4 (1M, 93 mL, 93 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 1 h and carefully quenched at 0 °C with a solution of KHS04 (10% aq.) and stirred for 0.5 h. The reaction mixture was diluted with aq. HCI (1 M, 150 mL) and extracted with CH2CI2 (3x200 mL), The combined organic layers were washed with aq. HCI (1 M), saturated NaHCC>3, brine,, and dried (MgS04). The mixture was filtered and concentrated in vacuo to yield XXHIe as a viscous colorless oil (14 g). Step 5. A solution of the aldehyde XXIHe (14 g, 61.6 mmol) in CH2CI2 (50 mL), was treated with Et3N (10.73 mL, 74.4 mmol), and acetone cyanohydrin (10.86 g, 127.57 mmol) and stirred at room temperature for 24 hrs. The reaction mixture was concentrated in vacuo and diluted with aq. HCI (1 M, 200 mL) and extracted into CH2CI2 (3x200 mL). The combined organic layer were washed with H20, brine, dried (MgSCU), filtered, concentrated in vacuo and purified by chromatography (Si02, EtOAc/Hex 1:4) to yield XXIIIf (10.3 g) as a colorless liquid Step 6. Methanol saturated with HCI*, prepared by bubbling HCI gas to CH3OH (700 ml) at 0 °C, was treated with cyanohydrin XXIIIf and heated to reflux for 24 h. The reaction was concentrated in vacuo to yield XXIIIg, which was used in the next step without purification. * Alternatively 6M HCI prepared by addition of AcCI to dry methanol can also be used. Step 7. A solution of the amine hydrochloride XXIIIg in CH2CI2 (200 mL) was treated with Et3N (45.0 mL, 315 mmol) and Boc20 (45.7g, 209 mmol) at -78 °C. The reaction mixture was then stirred at room temperature overnight and diluted with HCI (2 M, 200 mL) and extracted into CH2CI2. The combined organic layer were dried (MgS04) filtered, concentrated in vacuo and purified by chromatography (EtOAc/Hex 1:4) to yield hydroxy ester XXIIIh. Step 8. A solution of methyl ester XXIIIh (3g, 10,5 mmol) in THF/H20 (1:1) was treated with LiOH«H20 (645 mg, 15.75 mmol) and stirred at rt. for 2 h. The reaction mixture was acidfied with aq HCI (1 M, 15 mL) and concentrated in vacuo. The residue was dried in vacuum. A solution of the acid in CH2CI2 (50. mL) and DMF (25 mL) was treated with NH4CI (2.94 g, 55.5 mmol), EDCI (3.15 g, 16.5 mmol), HOOBt (2.69 g, 16.5 mmol), and NMM (4.4 g, 44 mmol). The reaction mixture was stirred at room temperature for 3 d. The solvents were removed under vacuo and the residue was diluted with aq. HCI (250 mL) and extracted with CH2CI2. The combined organic layers were washed with aq. Sat'd. NaHC03, dried (MgS04) filtered concentrated in vacuo to obtain XXIIIi, which was used as it is in the following steps. (Alternatively XXIIIi can also be obtained directly by the reaction of XXHIf (4.5 g, 17.7 mmoi) with aq. H202 (10 mL), LiOhUH20 (820 mg, 20.8 mmol) at 0 °C in 50 mLofCH3OHfor0.5h.) Step 9. A solution of XXIIIi obtained in the previous step was dissolved in 4 N HCI in dioxane and stirred at it for 2 h. The reaction mixture was concentrated in vacuo to give XXIIIj as a solid, which was used without further purification. Step 10. The amino ester XXIIII was prepared following the method of R. Zhang and J. S. Madalengoitia (J. Org. Chem. 1999, 64, 330), with the exeception that the Boc group was cleved by the reaction of the Boc-protected amino acid with methanolic HCI. A solution of commercial amino acid Boc-Chg-OH, XXHIk (Senn chemicals, 6.64 g, 24.1 mmol) and amine hydrochloride XX1III (4.5 g, 22 mmol) in CH2CI2 (100 mL) at 0 °C was treated with BOP reagent and stirred at rt. for 15 h. The reaction mixture was concentrated in vacuo, then it was diluted with aq. 1 M HCI and extracted into EtOAc (3x200 mL). The combined organic layers were washed with sat'd. NaHC03 (200 mL), dried (MgS04), filtered and concentrated in vacuo, and chromatographed (Si02, EtOAc/Hex 3:7) to obtain XXIIIm (6.0 g) as a colorless solid. Step 11. A solution of methyl ester XXIIIm (4.0 g, 9.79 mmol) in THF/H20 (1:1) was treated with LiOH«H20 (401 mg, 9.79 mmol) and stirred at rt. for 3 h. The reaction mixture was acidified with aq. HCI and concentrated in vacuo to obtain the free acid. A solution of acid (1.5 g, 3.74 mmol) in DMF/CH2CI2 (1:1 50mL) was treated with amine XXIHj (772 mg, 3.74 mmol), EDCI (1.07 g, 5.61 mmol), HOOBt (959 mg , 5.61 mmol) and NMM (2.15 mL, 14.96 mmol) at -10 °C. The reaction mixture was stirred at 0 °C for 48 h and concentrated in vacuo. The residue was diluted with aq. 1M HCI and extracted with CH2CI2, The combined organic layers were extracted with aq. NaHC03, aq. HCI, brine, dried (MgS04), filtered and concentrated in vacuo to obtain XXIIIn (2.08 g) as a tan colored solid. Step12, A solution of amide XXIHn (2.08 g, 3.79 mmol) in toluene and DMSO (1:1 20 mL) at 0 °C was treated with EDCi (7.24 g, 37.9 mmof) and dichloroacetic acid (2.42 g, 19.9 mmol) and stirred at rt for 4 h. The reaction mixture was diluted with CH2CI2) washed with sat'd. NaHCC>3, and brine. The organic layer were dried (MgS04) filtered, concentrated, in vacuo and purified by chromatography (S1O2, Acetone/Hexanes 3:7) to yield XXIII as a colorless solid. Example XXIV Preparation of a Compound of Formula XXIV: Step 1. XXIVa XXmi XXIVb A solution of Boc-tert-Lue XXIVa (Fluka, 5.0 g 21.6 mmol) in dry CH2CI2/DMF (50 mL, 1:1 ) was cooled to 0 °C and treated with the amine XXIHt (5.3 g, 25.7 mmol), NMM (6.5 g, 64.8 mmol) and BOP reagent (11.6 g, 25.7 mmol). The reaction was stirred at it for 24h, diluted with aq. HCI (1 M) and extracted with CH2CI2. The combined organic layers were washed with HCL (aq, 1 M), sat'd. NaHC03, brine, dried (MgS04), filtered and concentrated in vacuo and purified by chromatography (Si02, Acetone/Hexane 1:5) to yield XXIVb as a * colorless solid. Step 2. A solution of methyl ester XXIVb (4.0 g, 10.46 mmol) was dissolved in HCI (4 M soln. dioxane) and stirred at rt. for 3 h. The reaction mixture was concentrated in vacuo to obtain the amine hydrochloride salt used in the next step. A solution of the amine hydrochloride salt (397 mg, 1.24 mmol) in CH2CI2 (10 mL) was cooled to -78 °C and treated with ferf-butyi isocyanate (250 mg, 2.5 mmol) and stirred at rt. overnight. The reaction mixture was concentrated in vacuo and the residue was diluted with aq. HCI (1M) and extracted with CH2CI2. The combined organic layers were washed with aq. HCI (1M), sat'd. NaHC03 and brine. The organic layers were dried, filtered and concentrated in vacuo and the residue was purified by chromatography (Si02, acetone/Hex 1:4) to yield XXIVc as a colorless solid. Step 3. A solution of methyl ester XXIVc (381 mg, 1.0 mmol) in THF/H20 (1:1,5 mL) was treated with LiOH*H20 (62 mg, 1.5 mmol) and stirred at it for 3 h. The reaction mixture was acidified with aq. HCI and concentrated in vacuo to obtain the free acid. A solution of acid (254.9 mg, 0.69 mmol) in DMF/CH2CI2 (1:1, 5.0 mL) was treated with amine XXIIIj (159 mg, 0.763 mmol), EDCI (199 mg, 1.04 mmol), HOOBt (169.5 mg , 1.04 mmol) and NMM (280 mg, 2,77 mmol) at -20 °C. The reaction mixture was stirred at -20 °C for 48 h and concentrated in vacuo. The residue was diluted with aq. 1M HCI and extracted with EtOAc, The combined organic layers were extracted with aq. NaHC03, aq. HCI, brine, dried (MgS04) filtered concentrated in vacuo to obtain XXIVd (470 mg) as a tan colored solid. Step 4. A solution of amide XXlVd (470 mg, 0.9 mmol) in toluene and DMSO (1:1 20 mL) at 0 °C was treated with EDCI (1.72 g, 9,0 mmol) and dichloroacetic acid (0.37 mL, 4.5 mmol) and stirred at 0 °C for 4h. The reaction mixture was diluted with CH2CI2, and washed with satd. NaHCC>3, and brine. The organic layer was dried (MgS04), filtered, concentrated, in vacuo and purified by chromatography (Si02, Acetone/Hexanes 3:7) to yield XXIV as a colorless solid. Example XXV Prepration of a compound of Formula XXV: Step 1. A solution of Fmoc-glycine (Bachem, 2.0 g, 6.87 mmol) in CH2CI2 (20 mL) was treated with 2-phenyl-2-propanol (Aldrich, 3.36 g, 24.7 mmol), DCC (1M soln CH2CI2, 8.24 mL), DMAP (167 mg, 1.37 mmol) and stirred at rt. for 24 h. The reaction mixture was concentrated in vacuo and diluted with Et20 (100 mL). The solid seperating out was filtered and the filterate was washed with satd. NaHC03. The organic layer was dried (MgSC>4), filtered, concentrated in vacuo, and purified by chromatography (Si02, EtOAc/Hex 1:5) to yield ester XXVc (1.1 g) as a colorless viscous liquid. Step 2. A solution of XXVc in CH2CI2 (16.0 mL) was treated with piperidine (4.0 mL) and stirred at rt. for 0.5 h. The reaction mixture was concentrated in vacuo and purified by chromatography (Si02, Acetone/Hexanes 1:10 to 1:1) to yield the amine XXVd (420 mg) as a colorless liquid. A solution of methyl ester XXIVc (381 mg, 1.0 mmol) in THF/H20 (1:1,5 mL) was treated with LiOH*H20 (62 mg, 1.5 mmol) and stirred at rt. for 3 h. The reaction mixture was acidified with aq. HCI and concentrated in vacuo to obtain the free acid. A solution of acid (2.0 g, 5.5 mmol) in DMF/CH2CI2 (1:1,40.0 mL) at -10 °C was treated with amine XXIIIg (1.51 g, 6.8 mmol), EDCI (1.57 g, 8.25 mmol), HOOBt (1*41 g, 8.25 mmol) and NMM (2.5 g, 24.7 mmol). The reaction mixture was stirred at 0 "C for 48 h and concentrated in vacuo. The residue was diluted with aq. 1M HCI (100 mL) and extracted with CH2CI2 (3x100 mL). The combined organic layers were extracted with aq. NaHCCb, aq. HCI, brine, dried (MgSO-O filtered, concentrated in vacuo to obtain XXVe (3.17 g) as a tan colored solid used further without any purification. Step 4. A solution of methyl ester XXVe (2.5 g, 4.66 mmol) in THF/H20/CH3OH (1:1:1, 60 mL) was treated with LiOH«H20 (200 mg, 4.87 mmol) and stirred at it for 4 h. The reaction mixture was acidified with aq. HCI and concentrated in vacuo to obtain the free acid. A solution of acid (200.0 mg, 0.38 mmol) in DMF/CH2CI2 (1:1, 6.0 mL) at -10 °C was treated with amine XXVd (78 mg, 0.4 mmol), EDCI (105 mg, 0.55 mmol), HOOBt (95 mg, 0.55 mmol) and NMM (150 mg, 1.48 mmol). The reaction mixture was stirred at 0 °C for 48 h and concentrated in vacuo. The residue was diluted with aq. 1M HCI (30 mL) and extracted with CH2CI2 (3x30 mL). The combined organic layers were extracted with aq. NaHC03 (2x30 mL), aq. HCI, brine (30 mL), dried (MgS04) filtered, concentrated in vacuo to obtain XXVf (240 mg) as a tan colored solid. Step 5. A solution of XXVf (240 mg, 0.28 mmol) in CH2CI2 (10 mL) was treated with Dess-Martin reagent (Omega, 242 mg, 0.56 mmol) and stirred at rt. for 2 h. After the oxidation was complete (TLC, Acetone/Hex 1:4) the reaction mixture was diluted with satd. NaHC03 (20 mL) and Na2S203 (10% aq soln, 20 mL). The reaction mixture was stirred for 30 min and extractred with CH2CI2 (3x30 mL). The combined organic layers were extracted with satd. NaHC03, brine, dried (MgS04) filtered concentrated in vacuo and purified by chromatography (Si02, acetone/Hexanes 1:5) to yield XXV (122 mg) as a colorless solid. Example XXVI Preparation of a compound of Formula XXVI: To a stirred solution of /V-Boc-3,4-dehydroproline XXVIa (5.0 g, 23.5 mmol), di-terf-butyl dicarbonate (7.5 g, 34.4 mmol), and 4-A/,A/-dimethylaminopyridine (0.40 g, 3.33 mmol) in acetonitrile (100 mL) at room temperature was added triethylamine (5.0 mL, 35.6 mmol). The resulting solution was stirred at this temperature for 18 h before it was concentrated in vacuo. The dark brown residue was purified by flash column chromatography eluting with 10-25% EtOAc/hexane to give the product XXVIb as a pale yellow oil (5.29 g, 84%). Step 2: To a stirred solution of dehydroproline XXVIb (10.1 g, 37.4 mmoi), benzyltriethyiammonium chloride (1.60 g, 7.02 mmol) in chloroform (120 mL) at room temperature was added 50% aqueous sodium hydroxide (120 g). After vigorously stirred at this temperature for 24 h, the black mixture was diluted with CH2CI2 (200 mL) and diethyl ether (600 mL). After the layers were separated, the aqueous solution was extracted with CH2CI2/Et20 (1:2, 3x600 mL). The organic solution was dried (MgS04) and concentrated. The residue was purified by flash column chromatography using 5-20% EtOAc/hexane to afford 9.34 g (71%) of XXVIc as an off-white solid. Step 3: The solution of XXVIc (9.34 g, 26.5 mmoi) in CH2CI2 (25 mL) and CF3C02H (50 mL) was stirred at room temperature for 4.5 h before it was concentrated in vacuo to give a brown residue which was used in Step 4 without further purification. Step 4 Commercial concentrated hydrochloric acid (4.5 mL) was added to a solution of the residue from Step 3 in methanol (70 mL) and the resulting mixture was warmed to 65°C in an oil bath. After 18 h, the mixture was concentrated in vacuo to give a brown oil XXVIe, which was used in Step 5 without further purification. Step 5: To a stirred solution of proline methyl ester XXVIe from Step 4, commercial N-Boc-cyclohexylglycine XXVIf (10.2 g, 40.0 mmol) and [0-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate] (HATU) (16.0 g, 42.1 mmol) in DMF (200 mL) at 0°C was added diisopropylethylamine (18.0 mL, 104 mmol). After allowed to warm to room temperature along with the ice bath over night (18 h), the reaction mixture was diluted with EtOAc (600 mL), 5% H3PO4 (150 mL) and brine (150 mL). The organic solution was washed with 5% H3PO4 (150 mL), saturated NaHC03 (2x200 mL) before it was dried (MgS04), filtered and concentrated in vacuo. The residue was purified by flash column chromatography using 5-20% EtOAc/hexane to afford 3.84 g (32%, three steps) of XXVIg as an off-white solid. Step 6: The solution of methyl ester XXVIg (5.87g, 13.1 mmol-) and LiOH (1.65 g, 39.3 mmol) in THF/MeOH/H20 (1:1:1, 90 mL) was stirred at room temperature for 4 h. Methanol and THF were removed under reduced pressure. The aqueous solution was acidified to PH~2 using 1 N aqueous HCI solution (50 mL) and saturated with solid sodium chloride before it was extracted with EtOAc (3x150 mL). The organic solutions were combined, dried (MgSCU), filtered and concentrated in vacuo to give a white solid XXVIh (5.8 g, quantitative). Step 7: The desired product XXIlli was prepared according to the procedure in Example XXIII, Step 11. Step 8: manner previously described in Example IX, Step 2a to afford 0.66 g of the desired product XXVIIId-Step 3: The product of Step 2 (0.5g) was reacted with Dess-Martin reagent (1g) in the manner previously described in Example XX, Step 7. Purification by flash column chromatography (40% EtOAc, Hexane, silica) furnished 0.35g of product XXVIIIe. Mass spectrum (LCMS) 522 (M+H+). Step 4: The product of Step 4 (0.3g) was added a 1/1 H20/MeOH solution (20 mL) and NaHC03 solid (242 mg, 5equiv.). After being stirred for 18 hours at room temperature, the reaction was diluted with EtOAc and layers were separated. The aqueous layer was acidified to pH 2 with HC11.0 N and extracted with EtOAc. The EtOAc layer was washed with brine then dried over MgS04, filtered and concentrated in vacuo to afford product XXVIIIf as a white powder (0.26g). Mass spectrum (LCMS) 508 (M+H+). Step 5: The product of Step 5 (0.15g) was dissolved in CH2CI2 and reacted with HATU (0.137g), NH4CI (0.08g, 5equiv.) and DIPEA (0.53 mL). After 2 hours at room temperature, the reaction was diluted with EtOAc, washed with a 10% citric acid solution, then a saturated NaHCC>3 solution. The EtOAc layer was washed with brine then dried over MgS04, filtered and concentrated in vacuo to afford a crude mixture. Purification by flash column chromatography (30% Acetone, Hexane, silica) furnished the desired product XXVIII (0.096g). Mass spectrum (LCMS) 507 (M+H+). Example XXIX: Preparation of a compound of formula XXIX: Stepl: To a 0 °C solution of the starting aldehyde (4.0g) in CH2CI2 (75 mL) was added acetic acid (2.0 equiv., 2.15 mL) followed by methylisocyanoacetate (1.1 equiv., 1.9 mL). The reaction was then gradually warmed-up to room temperature. . After 18 hours (overnight), the reaction was diluted with EtOAc and washed with a saturated NaHC03 solution. The EtOAc layer was washed with brine then dried over MgSC>4, filtered and concentrated in vacuo to afford a crude mixture. Purification by flash column chromatography (30 to 40% EtOAc, Hexane, silica) furnished the product XXIXa (4.5g). Step2: To a 0 °C solution of XXIXa (4.4g) in THF (100 mL) was added 26 mL (2.2 equiv.) of a 1.0 N LiOH solution. The reaction was stirred at this temperature for 2 hours then warmed-up to room temperature. After 2 hours, reaction mixture was acidified to pH 2 with a 1.0 N HCI solution. EtOAc was added and layers were separated. The EtOAc layer was washed with brine then dried over MgS04, filtered and concentrated in vacuo to afford product XXIXb (3.7g). The acid XXIXb was reacted with the amine from Example XV in the manner previously described in Example XXI, Step 4. The resulting intermediate was then treated with HCI in the manner previously described in Example XXIII, Step 9 to afford product XXIXc. The acid XXVIIIc (2.43g) was dissolved in CH2CI2 and was reacted with amine XXIXc (2.47g), HATU (2.5g) and DIPEA (5.8 mL) in the manner previously described in Example IX, Step 2a to afford, after purification by flash column chromatography (4% MeOH, CH2CI2, silica), the desired product XXIXd (4.35g). Mass spectrum (LCMS) 727 (M+H+). Step 5: The product of Step 4 (4.2g) was reacted with Dess-Martin reagent (6.4g) in the manner previously described in preparative Example XX, Step 7. Purification by flash column chromatography (100% EtOAc, silica) furnished 3 g of the final product XXIX. Mass spectrum (LCMS) 725 (M+H+). Example XXX: Preparation of a compound of formula XXX: Step 1: The alcohol 2-(trifluoromethyi)propan-2-ol (1.28g) was reacted with N,N-disucciminidyl carbonate (3.84g) and E^N (4.2 mL) in dry CH3CN (50 mL) for 18 hours. The mixture was diluted with EtOAc (200 mL) and filtered. The filtrate was washed with NaHC03, brine then dried over MgS04, filtered and concentrated in vacuo to afford a crude mixture. Purification by flash column chromatography (50% EtOAc, Hexane, silica) furnished the desired product XXXa (0.3g). Step 2: XXXb The product from Example XXIX (0.3g) was treated with 100 mL of 4.0 N HCI in dioxane. After 1 h, 200 mL of Et20 were added and the resulting precipitate was filtered off and dried under vacuo to afford the product XXXb (0.27g) as a white powder. Mass spectrum (LCMS) 625 (M - HCI +H+). Step 3: To a room temperature solution of XXXb (0.05g) in CH2CI2 (5 ml_) was added DIPEA (0.040 ml_) XXXa (1.5 equiv., 0.030g), followed by 1 crystal of DMAP. After 30 minutes, reaction was diluted with EtOAc (20 ml_) and washed with HC11.5 N then NaHC03 then brine. EtOAc layer was dried over MgS04, filtered and concentrated in vacuo to afford a crude mixture. Purification by preparative chromatography (40% Acetone, Hexane, silica) furnished the desired product XXX (0.044g). Mass spectrum (LCMS) 779 (M+H+). Example XXXI: Preparation of a compound of formula XXXI: ! To a solution of XXXb (0.05g) in CH2CI2 (5 mL) at room temperature was added DIPEA (0.040 mL) and ferf-butylisocyanate (1.2 equiv., 0.01 mL). After 18 hours, reaction was diluted with EtOAc (20 mL) and washed with HC11.5 N, NaHC03 and brine. EtOAc layer was dried over MgSC>4, filtered and concentrated in vacuo to afford a crude mixture. Purification by preparative chromatography (100% EtOAc, silica) furnished the final product XXXI (0.021g). Mass spectrum (LCMS) 724 (M+H+). Example XXXII: Preparation of a compound of formula XXXII: The product from Example XXVIII was treated in the manner previously described in preparative Example XXX, Step 2 to afford product XXXIIa. Mass spectrum (LCMS) 407 (M - HCI +H+). Step 2: The amine XXXIIa was reacted with XXXa in the manner previously described in preparative Example XXX, Step 3 to afford the desired product XXXII. Mass spectrum (LCMS) 508 (M+H+). Example XXXIII: Preparation of a compound of formula XXXIII: Step 1: The amine XXXIla was reacted with terf-butylisocyanate in the manner previously described in Example XXXI, Step 1, to afford the product XXXIII. Mass spectrum (LCMS) 561 (M+H+). Example XXXIV: Preparation of a compound of formula XXXIV: To the mixture of ester (6.0g) and molecular sieve (5.2g) in anhydrous methylene chloride (35 mL) was aded pyrrolidine (5.7 mL, 66.36 mmoL). The resulting brown slurry was stirred at room temperature under N2 for 24 h, filtered and washed with anhydrous CH3CN. The combined filtrate was concentrated to yield the desired product. Step 2: To a solution of the product from proceeding step in CH3CN (35 mL) was added anhydrous K2C03, methallyl chloride (2.77g, 30.5 mmoL), Nal (1.07g, 6.7 mmoL). The resulting slurry was stirred at ambient temperature under N2 for 24 I 50 mL of ice-cold water was added followed by 2N KHSO4 solution until pH was EtOAc (100 mL) was added and the mixture was stirred for 0.75h. Combined organic layer was collected and washed with brine, dried over MgSC>4, and evaporated to yield the desired product. Step 3: The product from preceding step (2.7 g, 8.16 mmoL) was dissolved in dioxane (20 mL) and treated with freshly prepared 1N LiOH (9 mL). The reaction mixture was stirred at ambient temperature under N2 for 20 h. The reaction mixture was taken in EtOAc and washed with H20. The combined aqueous phas was cooled to 0°C and acidifed to pH 1.65 using 1N HCI. The turbid mixture was extracted with EtOAc (2 x 100 mL). Combined organic layer was washed with brine, dried over MgS04, concentrated to give the desired acid (3.40 g). Step 4: To a suspension of NaBH(OAc)3 (3.93g, 18.5 mmoL) in CH2C!2 (55 mL) was added a solution of product from preceding step in anhydrous CH2CI2 (20 mL) and acetic acid (2 mL). The slurry was stirred at ambient temperature for 20 h . Ice cold water (100 mL) was added to the slurry and stirred for 1/2 hr. Organic layer was separated, filtered, dried and evaporated to yield the desired'product. Step 5: To a solution of the product from preceding step (1.9g) in MeOH (40 mL) was treated with excess of CH2N2 / Et20 solution and stirred for overnight The reaction mixture was concentrated to dryness to yield a crude residue. The residue was chromatographed on silica gel, eluting with a gradient of EtOAc / hexane to afford 1.07 g of the pure desired product. Step 6: f To a solution of product from preceding step (1.36 g) in anhydrous CH2CI2 (40 mL) was treated with BF3. Me20 (0.7 mL). The reaction mixture was stirred at ambient temperature for 20 h and quenched with sat NaHC03 (30 mL) ad stirred for 1/2 hr. Organic layer was separated and combined organic layer was washed with brine, dried over MgS04, concentrated to give crude residue. The residue was chromotagraphed on silica gel eluting with a gradientof EtOAc / hexane to afford 0.88 g of the desired compound. Step 7: To a solution of the product (0.92 g) from preceding step in MeOH (30 mL) was added 10 % Pd/C (0.16 g) at room temperature and hydrogenated at ambient temperature under 1 atm. Pressure. The reaction mixture was stirred for 4 h and concentrated to dryness to yeild the desired compound. Step 8: The desired product XXXIV was prepared according to the procedure in Example XXIX, Steps 4-5. Example XXXV: Preparation of a compound of formula XXXV: A solution of triethyl phosphonate (44.8 g) in THF (30 mL) at 0°C wao treated with a 1M solution (200 mL) of sodium bis(trimethylsilylamide) in THF. The resulting mixture was stirred at RT for 0.5 hour, and then cooled to 0°C. A solution of 1,4-cyclohexanedione ethylene ketal (15.6 g) in THF (50 mL) was added dropwise, and the resulting solution was stirred at RT for 18 hours. The reaction mixture was then cooled to 0°C, treated with cold aqueous citric acid, and the mixture was extracted with EtOAc. The extract was washed with saturated aqueous NaHC03, then brine; then dried over anhydrous Na2S04, filtered, and the filtrate evaporated. The residue was chromatographed on silica gel, eluting with a gradient of CH2Cl2/EtOAc to afford the title compound (21 g), 92% yield. Mass spectrum (FAB) 227.3 (M+H+). Step 2: The product of the preceding step (20 g) was dissolved in EtOH'(150 mL) and treated with 10% Pd/C under 1 atm of hydrogen for 3 days. The mixture was filtered and the filtrate evaporated to afford the title compound (20.3 g), 100 % yield. Mass spectrum (FAB) 229.2 (M+hT). Step 3: The product of the preceding step (20 g) was dissolved in MeOH (150 mL) and treated with a solution of LiOH (3.6 g) in water (50 mL), The mixture was stirred for 18 hours, and concentrated under vacuum. The residue was dissolved in cold water (100 mL), the solution was acidified to pH 2-3 with 5N HCI, and the resulting mixture was extracted with EtOAc. The extract was dried over anhydrous Na2S04, filtered, and the filtrate evaporated to afford the title compound (17.1 g), 97% yield. Mass spectrum (FAB) 201.2 (M+H+). Step 4: 1. The product of the preceding step (3.0 g) was dissolved in Et20 (150 mL)f treated with Et3N (2.1 mL), and the solution cooled to -78°C. Pivaloyl chloride (1.85 mL) was added dropwise, and after 0.25 hour additional stirring, the reaction was allowed to warm to 0CC over 0.75 hour, and then cooled again to -78°C to afford a solution of mixed anhydride for reaction in part 2. .2. A solution of (S)-4-benzyl-2-oxazolidinone (2.66 g) in THF (22 mL) was cooled to -78°CI and a 1.6 M solution (9.38 mL) of n-butyilithium in hexane was added dropwise. After an additional 0.33 hour stirring at this temperature, the solution was transferred via canula to the cold solution of part 1. The mixture was stirred at -78°C f then warmed to 0°C, and stirred at this temperature for 0.5 hour. The organic layer was separated, the aqueous layer was extracted with Et20, the combined organics were washed with brine, dried over anhydrous Na2S04, filtered, and the filtrate evaporated. The residue was chromatographed on silica gel, eluting with a gradient of hexane/EtOAc (9:1) to afford the title compound (5.0 g), 93% yield. Mass spectrum (FAB) 360.4 (M+H+). Step 5: The product of the preceding step (2.7 g) was dissolved in THF (25 mL), cooled to -78°C, transferred by canula to a solution of 0.5 M potassium bis(trimethylsilyl)amide/toluene (16.5 mL) in THF (25 mL) at -78°C, and the resulting solution was stirred at -78°C for 0.75 hour. To this solution was added via canula a solution of trisyl azide (3,01 g) in THF (25 mL) pre-cooled to -78°C. After 1.5 minutes, the reaction was quenched with acetic acid (1.99 mL), the reaction was warmed to RT, and then stirred for 16 hours. The reaction was diluted with EtOAc (300 mL), and washed with 5% aqueous NaCI. The aqueous phase was extracted with EtOAc, the combined organic phases were washed with saturated aqueous NaHC03, then brine; then dried over anhydrous Na2S04, filtered, and the filtrate evaporated. The residue was chromatographed on silica gel, eluting with EtOAc/hexane (1:3) to afford the title compound (2.65 g), 88% yield. Step 6: The product of the preceding step (11.4 g) was dissolved in 95% formic acid (70 mL) and heated at 70°C for 0.5 hour while stirring. The solution was evaporated under vacuum, and the residue was taken up in EtOAc. The solution was washed with saturated aqueous NaHC03, then brine; then dried over anhydrous Na2S04, filtered, and the filtrate evaporated. The residue was chromatographed on silica gel to afford the title compound (8.2 g). Step 7: The product of the preceding step (8.2 g) was dissolved in CH2CI2 (16 mL) and treated with diethylaminosulfur trifiuoride (DAST, 7.00 mL) at RT for 3 hours. The reaction was poured over ice/water (200 cc), and extracted with CH2CI2. The extract was washed with saturated aqueous NaHC03, then brine; then dried over anhydrous Na2S04, filtered, and the filtrate evaporated. The residue was chromatographed on silica gel, eluting with EtOAc/hexane (15:85) to afford the title compound (4.5 g), 52% yield. Step 8: The product of the preceding step (3.7 g) was dissolved in a mixture of THF (150 mL) and water (48 mL), cooled to 0°C, treated with 30% H2O2 (3.95 mL), and then with UOH-H20 (0.86 g). The mixture was stirred for 1 hour at 0°C, then quenched with a solution of Na2S03 (5.6 g) in water (30 mL), followed by a solution of 0.5 N NaHC03 (100 mL). The mixture was concentrated under vacuum to 1/2 volume, diluted with water (to 500 mL), and extracted with CH2CI2 (4 x 200 mL). The aqueous phase was acidified to pH 1-2 with 5N HCl, and > extracted with EtOAc (4 x 200 mL). The extract was washed brine; then dried over anhydrous Na2S04, filtered, and the filtrate evaporated to afford the title compound (1.95 g), 91% yield, which was used directly in the next step. Step 9: The product of the preceding example (2.6 g) was dissolved in Et20 (50 mL) and treated dropwise with a solution of CH2N2 in Et20 until the solution remained yellow. The solution was stirred for 18 hours, then evaporated under vacuum to afford the title compound (2.8), which was used directly in the next step. Step 10: The product of the preceding step (1.95 g) was dissolved in MeOH (150 mL), treated with formic acid (1.7 mL), then treated with 10% Pd/C (3.3 g, Degussa type E101) under 1 atm of hydrogen for 1.5 hours. The mixture was filtered and the filtrate evaporated to afford the title compound (2.1 g) as the formic acid salt, which was used directly in the next step. Step 11: The product of the preceding step (2.1 g) was dissolved in 1,4-dioxane (100 mL) and di-terf-butyl dicarbonate (1.9 g) was added, followed by diisopropylethylamine (2.9 mL). The solution was stirred for 18 hours, and concentrated under vacuum. The residue was treated with aqueous 5% KH2PO4 and the mixture extracted with EtOAc. The extract was washed with brine; then dried over anhydrous MgS04, filtered, and the filtrate evaporated. The residue was chromatographed on silica gel, eluting with a gradient of CH2Cl2/Et20 to afford the title compound (2.5 g), 99% yield. Mass spectrum (FAB) 307.9 (M+H+), Step 12: The product of the preceding step (2.5 g) was dissolved in 1,4-dioxane (35 mL), treated with aqueous 1M LiOH (17 mL), and stirred for 2 hours. The mixture was quenched with ice/water (125 cc)fc the mixture was acidified to pH 3-4 with 3N HCI, and extracted with EtOAc. The extract was dried ove*- anhydrous MgS04, filtered, and the filtrate evaporated to afford the title compound (2.3 g), 96% yield. Mass spectrum (FAB) 294.0 (M+H+). Step 13: f XXXVIa XXXV,b To a solution of Compound XXXVIa ( 6.58g, 22 mmol) in 100 mL of MeOH was added 10% Pd/C (0.8 g) and p-toluene sulfonic acid (4.2 g). The reaction mixture was subjected to hydrogenation at room temperature overnight. The reaction mixture was filtered through celite and washed with excess MeOH. The combined filtrate was concentrated in-vacuo to provide the title compound XXXVIb as a gummy. Conversion of XXXVIb to XXXVI and XXXVII followed the route as shown in the scheme above and according to preparative examples 11-15. Example XXXVlll, Preparation of a compound of formula XXXVlll: A compound of the formula XXXVlll was prepared utilizing the following scheme and following preparative Examples 1-1 through 15 discussed earlier. A solution of the sulfonyl chloride XXXIXa prepared by the procedure of H. Mcklwain (J. Chem. Soc 1941, 75) was added dropwise to a mixture of 1.1. equiv of t-butylmethylamine and triethylamine at -78 °C and stirred at rt for 2h. The reaction mixture was concentrated in vacuo and purified by chromatography (SiC>2, Hex/Acetone 4:1) to yield sulfonamide XXXIXb as a colorless oil. Step 2: A solution of the Cbz-protected amine XXXIXb was dissolved in methanol and treated with 5 mo!% of Pd /C (5%w/w) and hydrogenated at 60 psi. The reaction mixture was filtered through a plug of celite and concentrated in vacuo to obtain the free amine XXXIXc which solidfied on standing. Step 3: The hydroxy sulfonamide XXXIXd was synthesized similar to the procedure for the synthesis of XXVf except replacing the amine XXVd with XXXIXc. The crude reaction mixture directly used for the next reaction. Step 4: The hydroxy amide XXXIXd was oxidized to compound XXXIX using the Dess Martin reagent following the procedure for the synthesis of XXV (step 5). The crude mixture was purified by chromatography (SiC>2, Acetone/Hexane 3:7) to obtain XXXIX as a colorless solid. Assay for HCV Protease Inhibitory Activity: Spectrophotometric Assay: Spectrophotometric assay for the HCV serine protease was performed on the inventive compounds by following the procedure described by R. Zhang et a/, Analytical Biochemistry, 270 (1999) 268-275, the disclosure of which is incorporated herein by reference. The assay based on the proteolysis of chromogenic ester substrates is suitable for the continuous monitoring of HCV NS3 protease activity. The substrates were derived from the P side of the NS5A-NS5B junction sequence (Ac-DTEDWX(Nva), where X = A or P) whose C-terminal carboxyl groups were esterified with one of four different chromophoric alcohols (3- or4-nitrophenol, 7-hydroxy-4-methyl-coumarin, or 4-phenylazophenol). Presented below are the synthesis, characterization and application of these novel spectrophotometric ester substrates to high throughput screening and detailed kinetic evaluation of HCV NS3 protease inhibitors. Materials and Methods: Materials: Chemical reagents for assay related buffers were obtained from Sigma Chemical Company (St. Louis, Missouri). Reagents for peptide synthesis were from Aldrich Chemicals, Novabiochem (San Diego, California), Applied Biosystems (Foster City, California) and Perseptive Biosystems (Framingham, Massachusetts). Peptides were synthesized manually or on an automated ABi model 431A synthesizer (from Applied Biosystems). UVA/IS Spectrometer model LAMBDA 12 was from Perkin Elmer (Norwalk, Connecticut) and 96-well UV plates were obtained from Corning (Coming, New York). The prewarming block was from USA Scientific (Ocala, Florida) and the 96-well plate vortexer was from Labline Instruments (Melrose Park, Illinois). A Spectramax Plus microtiter plate reader with monochrometer was obtained from Molecular Devices (Sunnyvale, California). Enzyme Preparation: Recombinant heterodimeric HCV NS3/NS4A protease (strain 1a) was prepared by using the procedures published previously (D. L. Sali et a/, Biochemistry, 37 (1998) 3392-3401). Protein concentrations were determined by the Biorad dye method using recombinant HCV protease standards previously quantified by amino acid analysis. Prior to assay initiation, the enzyme storage buffer (50 mM sodium phosphate pH 8.0, 300 mM NaCI, 10% glycerol, 0.05% lauryl maltoside and 10 mM DTT) was exchanged for the assay buffer (25 mM MOPS pH 6.5, 300 mM NaCI, 10% glycerol, 0.05% lauryl maltoside, 5 |jM EDTA and 5 pM DTT) utilizing a Biorad Bio-Spin P-6 prepacked column. Substrate Synthesis and Purification: The synthesis of the substrates was done as reported by R. Zhang et a/, (ibid.) and was initiated by anchoring Fmoc-Nva-OH to 2-chlorotrityl chloride resin using a standard protocol (K. Barlos et al, Int. J. Pept Protein Res., 37 (1991), 513-520). The peptides were subsequently assembled, using Fmoc chemistry, either manually or on an automatic ABI model 431 peptide synthesizer. The N-acetylated and fully protected peptide fragments were cleaved from the resin either by 10% acetic acid (HOAc) and 10% trifluoroethanol (TFE) in dichloromethane (DCM) for 30 min, or by 2% trifluoroacetic acid (TFA) in DCM for 10 min. The combined filtrate and DCM wash was evaporated azeotropically (or repeatedly extracted by aqueous Na2C03 solution) to remove the acid used in cleavage. The DCM phase was dried over Na2S04 and evaporated. The ester substrates were assembled using standard acid-alcohol coupling procedures (K. Holmber et a/, Acta Chem. Scand., JB33 (1979) 410-412). Peptide fragments were dissolved in anhydrous pyridine (30-60 mg/ml) to which 10 molar equivalents of chromophore and a catalytic amount (0.1 eq.) of para-toluenesulfonic acid (pTSA) were added. Dicyclohexylcarbodiimide (DCC, 3 eq.) was added to initiate the coupling reactions. Product formation was monitored by HPLC and found to be complete following 12-72 hour reaction at room temperature. Pyridine solvent was evaporated under vacuum and further removed by azeotropic evaporation with toluene. The peptide ester was deprotected with 95% TFA in DCM for two hours and extracted three times with anhydrous ethyl ether to remove excess chromophore. The deprotected substrate was purified by reversed phase HPLC on a C3 or C8 column with a 30% to 60% acetonitrile gradient (using six column volumes). The overall yield following HPLC purification was approximately 20-30%. The molecular mass was confirmed by electrospray ionization mass spectroscopy. The substrates were stored in dry powder form under desiccation. Spectra of Substrates and Products: Spectra of substrates and the corresponding chromophore products were obtained in the pH 6.5 assay buffer. Extinction coefficients were determined at the optimal off-peak wavelength in 1-cm cuvettes (340 nm for 3-Np and HMC, 370 nm for PAP and 400 nm for 4-Np) using multiple dilutions. The optimal off-peak wavelength was defined as that wavelength yielding the maximum fractional difference in absorbance between substrate and product (product OD - substrate OD)/substrate OD). Protease Assay: HCV protease assays were performed at 30°C using a 200 pi reaction mix in a 96-well microliter plate. Assay buffer conditions (25 mM MOPS pH 6.5, 300 mM NaCI, 10% glycerol, 0.05% lauryi maltoside, 5 pM EDTA and 5 pM DTT) were optimized for the NS3/NS4A heterodimer (D. L. Sali et a/, ibid.)). Typically, 150 pi mixtures of buffer, substrate and inhibitor were placed in wells h (final concentration of DMSO 4 % v/v) and allowed to preincubate at 30 °C for approximately 3 minutes. Fifty pis of prewarmed protease (12 nM, 30°C) in assay buffer, was then used to initiate the reaction (final volume 200 pl).The plates were monitored over the length of the assay (60 minutes) for change in absorbance at the appropriate wavelength (340 nm for 3-Np and HMC, 370 nm for PAP, and 400 nm for 4-Np) using a Spectromax Plus microtiter plate reader equipped with a monochrometer (acceptable results can be obtained with plate readers that utilize cutoff filters). Proteolytic cleavage of the ester linkage between the Nva and the chromophore was monitored at the appropriate wavelength against a no enzyme blank as a control for non-enzymatic hydrolysis. The evaluation of substrate kinetic parameters was performed over a 30-foid substrate concentration range (-6-200 pM). Initial velocities were determined using linear regression and kinetic constants were obtained by fitting the data to the Michaelis-Menten equation using non-linear regression analysis (Mac Curve Fit 1.1, K. Raner). Turnover numbers (/feat) were calculated assuming the enzyme was fully active. • Evaluation of Inhibitors and Inactivators: The inhibition constants (Ki*) for the competitive inhibitors Ac-D-(D-Gia)-L-l-(Cha)-C-OH (27), Ac-DTEDWA(Nva)-OH and Ac-DTEDWP(Nva)-OH were determined experimentally at fixed concentrations of enzyme and substrate by plotting VQ/VJ VS. inhibitor concentration ([I] 0) according to the rearranged Michaelis-Menten equation for competitive inhibition kinetics: Vo/Vj = 1 + [|] 0 /(Ki* (1 + [S] 0 /Km)), where v0 is the uninhibited initial velocity, Vj is the initial velocity in the presence of inhibitor at any given inhibitor concentration ([l]0) and [S]0 is the substrate concentration used. The resulting data were fitted using linear regression and the resulting slope, 1/(Ki*(1+[S]o/Km), was used to calculate the Ki* value. The obtained Ki* values for the various compounds of the present invention are given in the afore-mentioned Tables wherein the compounds have been arranged in the order of ranges of Ki* values. From these test results, it would be apparent to the skilled artisan that the compounds of the invention have excellent utility as NS3-serine protease inhibitors. While the present invention has been described with in conjunction with the specific embodiments set forth above, many alternatives, modifications and other variations thereof will be apparent to those of ordinary skill in the art. All such alternatives, modifications and variations are intended to fall within the spirit and scope of the present invention. WE CLAIM: 1. A compound, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound having the general structure shown in Formula I: Formula I wherein: Y is selected from the group consisting of the following moieties: alkyl, alkyl-aryl, heteroalkyl, heteroaryl, aryl-heteroaryl, alkyl-heteroaryl, cycloalkyl, alkyloxy, alkyl-aryloxy, aryloxy, heteroaryloxy, heterocycloalkyloxy, cycloalkyloxy,, alkylamino, arylamino, alkyl-arylamino, arylamino, heteroarylamino, cycloalkylamino and heterocycloalkylamino, with the proviso that Y may be optionally substituted with XuorX12; X11 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, heterocyclyl, heterocyclylalkyl, aryl, alkylaryl, arylalkyl, heteroaryl, alkylheteroaryl, or heteroarylalkyl, with the proviso that X may be additionally optionally substituted withX12; X12 is hydroxy, alkoxy, aryloxy, thio, alkylthio, arylthio, amino, alkylamino, arylamino, alkylsulfonyl, arylsulfonyl, alkylsulfonamido, arylsulfonamido, carboxy, carbalkoxy, carboxamido, alkoxy carbonylamino, alkoxy carbonyloxy, alkylureido, arylureido, halogen, cyano, or nitro, with the proviso that said alkyl, alkoxy, and aryl may be additionally optionally substituted with moieties independently selected from X12; R1 is COR5, wherein R5 is COOR8, CONR9R10, CF3, C2F5, C3F7, CF2R6, or R6, wherein R6, R8, R9 and R10 are independently selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl, [CH(Rr)]pCOORn, [CH(Rr)]pCONR12R13, [CH(R1')]pS02R11, [CH(R1')]pCORn, [CH(Rr)]pCH(OH)Rn, CH(Rr )CONHCH(R2' )COO R11, CH(R1')CONHCH(R2')CONR12R13, CH(Rr)CONHCH(R2' )R', CH(Rr)CONHCH(R2')CONHCH(R3)COO R11, CH(Rr)CONHCH(R2)CONHCH(R3')CONR12R13, CH(R1')CONHCH(R2')CONHCH(R3')CONHCH(R4')COOR11, CH(R1')CONHCH(R2')CONHCH(R3')CONHCH(R4')CONR12R13, CH(Rr)CONHCH(R2' )CONHCH(R3')CONHCH(R4')CONHCH(R5')COO R11 and CH(Rr )CONHCH(R2' )CONHCH(R3')CONHCH(R4')CONHCH(R5') CONR12R13, wherein R1', R2', R3', R4', R5', R11, R12, and R13 are independently selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, alkyl-aryl, alkyl- heteroaryl, aryl-alkyl and heteroaralkyl; Z is selected from O, N, CH or CR; W may be present or absent, and if W is present, W is selected from C=0, C=S, C(^-CN),orS02; Q may be present or absent, and when Q is present, Q is CH, N, P, (CH2)P, (CHR)P , (CRR')P, O, NR, S, or S02; and when Q is absent, M may be present or absent; when Q and M are absent, A is directly linked to L; A is O, CH2, (CHR)p , (CHR-CHR')P, (CRR')P, NR, S, or S02; E is CH, N, CR, or a double bond towards A or L; G is absent, and E is directly connected to the carbon atom in Formula I as G is linked to; J is present, J is (CH2)P, (CHR)P, or (CRR')P, S02, NH, NR or O; L is present, L is CH, CR, O, S or NR; M may be present or absent, and when M is present, M is O, NR, S, S02, (CH2)p, (CHR)P (CHR-CHR')P, or (CRR')P; p is a number from 0 to 6; and R, R\ R , R and R are independently selected from the group consisting of H; Cr Cio alkyl; C2-Ci0 alkenyl; C3-C8 cycloalkyl; C3-C8 heterocycloalkyl, alkoxy, aryloxy, alkylthio, arylthio, amino, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, halogen; (cycloalkyl)alkyl and (heterocycloalkyl)alkyl, wherein said cycloalkyl is made of three to eight carbon atoms, and zero to six oxygen, nitrogen, sulfur, or phosphorus atoms, and said alkyl is of one to six carbon atoms; aryl; heteroaryl; alkyl-aryl; and alkyl-heteroaryl; wherein said alkyl, heteroalkyl, alkenyl, heteroalkenyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl moieties may be optionally and chemically-suitably substituted, with said term "substituted" referring to optional and chemically-suitable substitution with one or more moieties selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl, heterocyclic, halogen, hydroxy, thio, alkoxy, aryloxy, alkylthio, arylthio, amino other than for R2, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, sulfonamido, sulfoxide, sulfone, sulfonyl urea, hydrazide, and hydroxamate; further wherein said unit N-C-E-L-J-N represents a five-membered or six-membered cyclic ring structure with the proviso that when said unit N-C-E-L-J-N represents a five-membered cyclic ring structure, or when the bicyclic ring structure in Formula I comprising N, C, E, L, J, N, A, Q, and M represents a five-membered cyclic ring structure, then said five-membered cyclic ring structure lacks a carbonyl group as part of the cyclic ring. 2. The compound of claim 1, wherein R1 is COR5, and R5 is COOR8 or CONR9R10. 3. The compound of claim 2, wherein R1 is COCONR9R10, and R9 is H, R10 is H, R14, [CHCR^JpCOOR11, [CH(R15)] pCONR12R13, [CH(Rr)]pS02Rn, [CH(Rr)]pCORn, CH(R1)CONHCH(R2)COOR11, CH(Rr)CONHCH(R2) CONR12R13, or CH(R^CONHCH(R2')(R*), wherein R14 is H, alkyl, aryl, heteroalkyl, heteroaryi, cycloalkyl, alkyl-aryl, alkyl-heteroaryl, aryl-alkyl, alkenyl, alkynyl or heteroaralkyl. 4. The compound of claim 3, wherein R10 is H, R14, CH^COOR11, CHl^^CHC^^COOR11, CH(R1)CONRl2R13, CH(Rr)CH(Rr)CONR12R13, CH(R1)CH(Rr)S02R11, CHCR^CH^SOsN R12R13, CH(R1')CH(R1')COR11, CH(Rl)CONHCH(R2)COORu, CH(Rr)CONHCH(R2') CONR12R13,or CH(R1')CONHCH(R2')(R'), wherein R1' is H or alkyl, and R2' is phenyl, substituted phenyl, hetero atom-substituted phenyl, thiophenyl, cycloalkyl, piperidyl or pyridyl. 5. The compound of claim 4, wherein R1 is H. 6. The compound of claim 5, wherein R11 is H, methyl, ethyl, allyl, terr-butyl, benzyl, a-methylbenzyl, a,a-dimethylbenzyl, 1-methylcyclopropyl or 1- methy ley clopenty 1; R' is hydroxymethyl or CH2CONR12R13; R2 is independently selected from the group consisting of: wherein: U1and U2 may be same or different and are selected from H, F, CH2COOH, CH2COOMe, CH2CONH2, CH2CONHMe, CH2CONMe2, azido, amino, hydroxyl, substituted amino, substituted hydroxyl; U3 and U4 may be same or different and are selected from O and S; U5 is selected from the moieties consisting of alkyl sulfonyl, aryl sulfonyl, heteroalkyl sulfonyl, heteroaryi sulfonyl, alkyl carbonyl, aryl carbonyl, heteroalkyl carbonyl, heteroaryl carbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl or a combination thereof; and NR12R13 is selected from the group consisting of: wherein U6 is H, OH, or CH2OH, and R14 is selected from the group consisting of: H, Me, Et, w-propyl, methoxy, cyclopropyl, n-butyl, l-but-3-ynyl, benzyl, a-methylbenzyl, phenethyl, allyl, l-but-3-enyl, OMe, cyclopropylmethyl. 7. The compound of claim 2, wherein R2 is selected from the group consisting of the following moieties: c Wherein G is absent and J is selected from the group consisting of (CH2)P, (CHR)P, (CHR-CHR')p, and (CRR')P; A and M are independently selected from the group consisting of O, S, S02, NR, (CH2) p, (CHR)P, (CHR-CHR')P, and (CRR')P; and Q is CH2, CHR, CRR\ NH, NR, O, S, S02, NR, (CH2) p, (CHR)P, and (CRR')p. 17. The compound of claim 16, wherein structure c is selected from the following structures: The pharmaceutically composition of claim 20 additionally comprising a pharmaceutical^ acceptable carrier. 23. The pharmaceutically composition of claim 22, additionally containing an antiviral agent. 24. The pharmaceutically composition of claim 23, further containing an interferon. 25. The pharmaceutically composition of claim 24, wherein said antiviral agent is ribavirin and said interferon is a-interferon orpegylated interferon. 26. A method of preparing a pharmaceutical composition for treating the disorders associated with the HCV, said method comprising bringing into intimate contact a compound of claim 1 and a pharmaceutical^ acceptable carrier. 27. A compound exhibiting HCV protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being selected from the compounds of structures listed below: A pharmaceutically composition for treating disorders associated with the HCV, said composition comprising therapeutically effective amount of one or more compounds in claim 27 and a pharmaceutically acceptable carrier. 29. The pharmaceutically composition of claim 28, additionally containing an antiviral agent. 30. The pharmaceutically composition of claim 29, still additionally containing an interferon or PEG-interferon alpha conjugate. 31. The pharmaceutically composition of claim 30, wherein said antiviral agent is ribavirin and said interferon is a-interferon. 32. An invitro method of modulating the activity of hepatitis C virus (HCV) Protease, comprising contacting HCV protease with one or more compounds of claim 27. 33. The methods of claims 32, wherein the HCV protease is the NS3/NS4a protease. 34. The method of claim 33, wherein the compound or compounds inhibit HCV ND3/NS4a protease. 35. A methods of modulating the processing of hepatitis C virus (HCV) polypeptide, comprising contacting a composition containing the HCV polypeptide under conditions in which the polypeptide is processed with one or more compounds of claim 27. 36. The compound of claim 8, wherein R3 is: 37. A compound exhibiting HCV protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: 38. A compound exhibiting HCV protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: 39. A compound exhibiting HCV protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: 40. A compound exhibiting HCV protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutical^ acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: 41. A compound exhibiting HCV protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prod rug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: 42. A compound exhibiting HCV protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: 43. A compound exhibiting HCVprotease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: 44. A compound exhibiting HCV protease inhibitory activity, including 'enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: 45. A compound exhibiting HCV protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being the compound of structure shown below: 46. A compound exhibiting HCV protease inhibitory activity, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, s or of said prodrug, said compound being the compound of structure shown below: 47. A pharmaceutical composition comprising as an active ingredient a compound, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts 10 or solvates of said compound, or of said prodrug, said compound being selected from the following: 48. The pharmaceutically composition of claim 47, additionally containing an antiviral agent. 49. The pharmaceutically composition of claim 48, still additionally containing an interferon or PEG-interferon alpha conjugate. 50. The pharmaceutical composition of claim 49, wherein said antiviral agent is ribavirin and said interferon is a-interferon. 51. A compound of claim 37, which has the formula shown below: 52. A compound of claim 37, which has the formula shown below: 53. A compound of claim 38, which has the formula shown below: 54. A compound of claim 38, which has the formula shown below: 72. The pharmaceutically composition of claim 71, additionally containing an antiviral agent. 73. The pharmaceutically composition of claim 72, additionally containing an interferon or pegylated-interferon alpha conjugate. 74. The pharmaceutically composition of claim 73, wherein said antiviral agent is ribavirin and said interferon is alpha-interferon. 75. A pharmaceutically composition comprising as an active ingredient a compound, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being selected from a compound of claim 1, said pharmaceutical composition further comprising an interferon. 76. The pharmaceutically composition of claim 75, wherein said interferon is alpha-interferon orpegylated interferon. 77. The pharmaceutically composition of claim 76, suitable for oral or subcutaneous administration. 78. A pharmaceutically composition comprising as an active ingredient a compound, including enantiomers, stereoisomers, rotamers, tautomers, racemates and prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being selected from a compound of claim 27, said pharmaceutical composition further comprising an interferon. 79. The pharmaceutically composition of claim 78, wherein said interferon is alpha-interferon or pegylated interferon. 80. The pharmaceutically composition of claim 79, suitable for oral or subcutaneous administration. 81. The pharmaceutically composition of claim 47, and an interferon. 82. The pharmaceutically composition claim 81, wherein said interferon is alpha-interferon or pegylated interferon. 83. The pharmaceutically composition of claim 82, suitable for oral or subcutaneous administration. 84. The pharmaceutically composition of claim 75, further comprising an antiviral agent. 85. A pharmaceutically composition comprising as an active ingredient a compound, including prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being selected from a compound of any one of claims 51-70, said pharmaceutical composition further comprising an interferon. 86. The pharmaceutically composition of claim 71 further comprising an interferon. 87. A pharmaceutically composition comprising as an active ingredient a compound, including prodrug of said compound, and pharmaceutically acceptable salts or solvates of said compound, or of said prodrug, said compound being selected from the

Documents:

089-chenp-2003-abstract.pdf

089-chenp-2003-assignement.pdf

089-chenp-2003-claims duplicate.pdf

089-chenp-2003-claims original.pdf

089-chenp-2003-correspondnece-others.pdf

089-chenp-2003-correspondnece-po.pdf

089-chenp-2003-description complete duplicate.pdf

089-chenp-2003-description complete original.pdf

089-chenp-2003-drawings.pdf

089-chenp-2003-form 1.pdf

089-chenp-2003-form 13.pdf

089-chenp-2003-form 26.pdf

089-chenp-2003-form 3.pdf

089-chenp-2003-form 5.pdf

089-chenp-2003-pct.pdf