Indian Patents. 257469:"C-3 ALKYL OR ARYLALKYL SUBSTITUTED 2,3-DIDEOXY GLUCOPYRANOSIDES AND A PROCESS FOR PREPARATION THEREOF"

Title of Invention	"C-3 ALKYL OR ARYLALKYL SUBSTITUTED 2,3-DIDEOXY GLUCOPYRANOSIDES AND A PROCESS FOR PREPARATION THEREOF"
Abstract	The present invention also relates to a novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides, a new series of anti-tubercular agents. Further these compounds being multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides derivatives are better from previously known anti-tubercular compounds.

Full Text	The present invention relates to a novel series of anti-tubercular multifunctionalized unsaturated C-3-alkyl or arylalkyl substituted 2,3-dideoxy glucopyranosides having general formula 6a and 6b respectively (FigureRemoved) wherein R represents aryl groups selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group , while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by p-nitrobenzoyl and different alkyl chlorides like ter/-butyldimethylsilyl and terf-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars and OR" as a whole represents thiol and all substituted thiols. The present invention also relates to a process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and - arylalkyl substituted 2,3-dideoxy glucopyranosides. This invention particularly relates to a process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and - arylalkyl substituted 2,3-dideoxy glucopyranosides, a new series of anti-tubercular agents. These unsaturated 2,3-dideoxy glucopyranosides of general formula 6a and 6b are new chemical compounds and they had not been prepared earlier. More specifically the present invention provides a process for the preparation of novel series of multifunctionalized unsaturated C-3-alkyl and - arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6a and 6b. These unsaturated C-3-alkyl and - arylalkyl substituted 2,3-dideoxy glucopyranosides are novel compounds and are useful as anti-tubercular agents. These compounds have been tested against M. tuberculosis H37RV by agar dilution method and some of these compounds have shown promising anti-tubercular activity. The invention thus relates to the pharmaceutical industry. Several of these novel compounds are showing promising anti-tubercular activity against M. tuberculosis //j/^by agar dilution method. Background of the present invention Tuberculosis (TB), a chronic bacterial infection is a leading cause of death worldwide, from a single infectious agent [(a) Dolin, P. J.; Raviglione, M. C.; Kochi, A. Bull. WHO 1994, 72, 213; (b) Huebner, R. E.; Castro, K. G. Ann. Rev. Med. 1995, 46, 47]. TB is caused by mycobacterium of the 'tuberculosis complex', including M. bovis, M. affricanum but mainly by M. tuberculosis [Pasqualoto, K. F. M.; Ferreira, E. I. Current Drug Target 2001, 2, 427]. According to WHO estimates roughly one-third of the world's population is latently infected with the tuberculosis bacteria [Farmer, P.; Bayona, J.; Becerra, M.; Furin, J.; Henry, C.; Hiatt, H.; Kim, J. Y.; Mitnick, C.; Nardell, E.; Shin, S. Int. J. Tuberc. LungDis. 1998, 2, 869]. It is a worse killer than malaria and AIDS combined. It is estimated that by 2020 A.D. nearly one billion more people will be infected, 200 million people will get sick and 70 million will die from tuberculosis if proper steps to control it are not taken. [ (a) Daffe, M.; Draper, P. Adv. Microb. Physiol 1998,39,131; (b) WHO Global tuberculosis programme- Tuberculosis Fact Sheet, 1998. (http://www.who.int/gtb/publication/index. htm#Report)]. In all, there are approximately 70 species in the genus Mycobacterium, many of which are opportunistic pathogens in humans and animals, while others like M. avium are emerging pathogens most notably in AIDS patients [Iran, T.; Saheba, E.; Arcerio, A.V.; Chavez, V.;Li, Q.; Martinez, L.E; Primm, T.P. Bioorg. Med. Chem. 2004,12,4809.]. The AIDS pandemic has had a big impact on worldwide TB prevalence. One-third of the increase in the incidences of the TB in the last 5 years can be attributed to co-infection with HIV [Rattan, A.; Kalia, A. and Ahmad, N. Emerg. Infect. Dis. 1998, 4, 195].The other factor responsible for increase in TB cases is the emergence of the so called MDR-TB, resistant to some or all currently known TB drugs. Emergence of MDR-TB is a result of lack of patient's compliance with long term chemotherapy, prescription of wrong drugs or wrong combination of drugs by doctors and health workers, unreliable drug supply, delay in diagnosis, variable efficacy of BCG vaccines and various other factors such as unavailability of drugs in remote areas of certain high risk regions, [(a) WHO Global tuberculosis programme- Tuberculosis Fact Sheet, 1998. [http://www.who.int/gtb/publication/index. htm#Report]. (b) WHO - Country Profiles: Brazil. Annual Report, 1997. [http://www.who.int]. (c) Rattan, A.; Kalia, A. and Ahmad, N. Emerg. Infect. Dis. 1998,4, 195. (d) Chopra, P., Meena, I. S., Singh, Y. Indian J. Med. ^-.,2003,7,117]. MDR-TB is becoming increasingly difficult and expensive to treat with an ever rising mortality rate that raises the specter that TB will once again become an incurable disease [Pathak, A. K.; Pathak, V.; Maddry, J. A.; Suling, W. J.;Gurcha, S. S.; Besra, G. S.; Reynolds, R. C. Bioorg. Med.Chem. 2001,9, 3145]. Current strategy for treatment of TB involves use of front line drugs like INH, rifampin, PZA and ethambutol for two months followed by four months of follow up treatment with INH and rifampin [Bass, J. B., Jr.; Farer, L. S.; Hopewell, P.C.; O'Brien, R.; Jacobs, R. F.; Ruben, F.; Snider, D. E., Jr.; Thornton, G., the American Thoracic Society. Am. J. Respir. Crit. Care Med. 1994,149, 1359]. However this combination therapy is not always successful in case of MDR suspected patients. The latest anti-TB drug was introduced almost 30 years ago when the problem of MDR-TB and co-infection with HIV did not exist and thus to effectively combat these problems there is an urgent need for development of new anti TB drugs that have unique mechanisms of action from presently used anti-tubercular drugs with improved properties such as enhanced activity against MDR strains [(a) Pathak, A. K.; Pathak, V.; Seitz, L.; Maddry, J. A.;Gurcha, S. S.; Besra, G. S.; Suling, W. J.; Reynolds, R. C.Bioorg. Med. Chem. 2001, P, 3129.(b) Pathak, A. K.; Pathak, V.; Maddry, J. A.; Suling, W. J.; Gurcha, S. S.; Besra, G. S.; Reynolds, R. C. Bioorg. Med. Chem. 2001, 9, 3145.(14) (c) C.A. no. 90: 152534y Wojtowicz, M; Wienlawski, W.Acta Pol. Pharm. 1978, 35, 37. (d) C.A. no. 89: 110253e Wojtowicz, M.; Wienlawski, W. Acta Pol. Pharm. 1977, 34, 575]. These molecules should be effective against latent TB, should have shortened duration of therapy thereby reducing chances of non-compliance of patients and should also ideally have reduced toxicity, rapid mycobactericidal mechanism of action and the ability to penetrate host cells and exert anti-mycobacterial effects in the intra cellular environments [Panda, G.; Siddiqui, S.; Mishra, J. K.; Chaturvedi, V.; Srivastava, A. K.; Srivastava, R.; Srivastava, B. Bioorg. Med. Chem. 2004,12, 5629]. The recent report [Cole, S.T.; Brosch, R.; Parkhill, J.; et al. Nature 1998, 393, 537] on complete genome sequence of Mycobacterium tuberculosis has provided a more rational and directional approach to the search for new drug targets. In general, gene products involved in mycobacterial metabolism, persistence, transcription, synthesis of cell-wall and virulence would be possible targets for the new drug development [Chopra, P., Meena, I. S., Singh, Y. Indian J. Med. Res., 2003,1,117]. The intrinsic resistance of the TB bacilli to antibiotics and chemotherapeutic agents can be ascribed to its unique and intricate cell wall structure which is made up of polysaccharides, proteins and lipids [Khasnobis, S.; Escuyer, V. E.; Chatterjee, D. Espert Opin.Ther. Targets 2002, 6,21]. The sugar components in these polysaccharides have been identified as L-rhamnose, D-arabinofuranose and D-galactofuranose which have no role in mammalian metabolism [Lee, R.E.; Smith, M.D.; Pickering, L.; Fleet, G.W. Tetrahedron Lett. 1999, 40, 8689] thus making the biochemistry and attendant enzyme pathways ideal targets for the development of new,potent and selective antimycobacterial agents [Pathak, A. K.; Pathak, V.; Maddry, J. A.; Suling, W. J.; Gurcha, S. S.; Besra, G. S.; Reynolds, R. C. Bioorg. Med. Chem. 2001, P, 3145]. Due to the easy availability of carbohydrates as sources of metabolic energy, their high tolerance [Fischer, J. F.; Harrison, A.W.; Bundy, G.L.; Wilkinson, K.F.; Rush, B.D.; Ruwart, M. J. J. Med. Chem. 1991, 34 , 4140], improved pharmacokinetics [Negre, E.; Chance, M. L.; Hanbuta, S. Y.; Monsigny, M.; Roche, A. C.; Mayer, R. M. Antimicrob. Agents Chemother. 1992, 35, 2228], better transport [Wolform, M. L.; Hanessian, S. J. Org. Chem. 1962, 27, 1800], low toxicity and their role in recognition phenomena many of which are of great pharmacological relevance [Cipolla, L.; Ferla, B. L.; Nicotra, F. Carbohydr. Polym. 1998, 37, 291], much effort is being focused towards the development of carbohydrate-based therapeutics during the last few years [McAuliffe, J.; Hindsgaul, 0. Chemistry and Industry 1997, 170]. However, current efforts are mainly directed towards the development of small molecules which are more stable, more active and whose synthesis can be easily developed [Wong, C-H. Acc.Chem. Res. 1999, 32, 376]. Certain sugar derivatives and glucofuranose analogues have been reported as antitubercular agents recently [(a) Tripathi, R.P.; Tewari, N.; Dwivedi, N.; tewari, V. K. Medicinal Research Reviews 2005, 25, 93. (b) Maddry, J. A.; Bansal, N.; Bermudez, L. E.; Comber, R.N.; Orme, W. J.; Suling, W. J.; Wilson, L. N.; Raynolds, R. C. Bioorg. Med. Chem. Lett. 1998, 8, 237. (c) John, T.B.; Varalakshmi, D.; Todd, S.; Takayama, K.; Patrick, J. B.; Besra, G.S. Science 1997, 39, 1420. (d) Chung, G. A.; Aktar, Z.; Jackson, S.; Duncan, K. Antimicrob. Agents Chemother. 1995,39,2235. (e) Namane, M.; Goujette, C.; Pillion, M.P.; Pillion, J.; Huynh, T.; Dinh, J. J. Med. Chem. 1992, 35, 3039]. During the past decades, deoxysugars, a distinct class of carbohydrates, have received special attention due to their thermal stability, hydrophobicity and important role in lipopolysaccharides, glycoproteins, and glycolipids, where they serve as ligands for cell-cell interactions or as targets for toxins, antibiotics and microorganisms [Hallis, T. M.; Liu, H-W. Ace Chem.Res. 1999,32,579]. In our ongoing programme on the search of new anti-tubercular agents we have been focusing our efforts on the synthesis of easily available monosaccharide derived anti-tubercular agents [(a) Gupta, M. K.; Sagar, R.; Shaw, A.K.; Prabhakar, Y. S. Bioorg. Med.Chem.2005,13,343. (b) Pathak, R.; Pant, C. S.; Shaw, A. K.; Bhaduri, A. P.; Gaikwad, A. N.; Sinha, S.; Srivastava, A.; Srivastava, K. K.; Chaturvedi, V.; Srivastava, R.; Srivastava, B. S. Bioorg. Med. Chem.20Q2, 10, 3187. (c) Pathak, R.; Shaw, A. K.; Bhaduri, A. P.; Chandrasekhar,K. V. G.; Srivastava, A.; Srivastava, K. K.; Chaturvedi, V.;Srivastava, R.; Srivastava, B. S.; Arora, S.; Sinha, S. Bioorg. Med.Chem.2W2,l 0,1695]. These molecules are chain extended acyclic or cyclic deoxysugar derivatives. We found from the literature survey on antimicrobial activity of cyclic deoxysugars that 2//-pyran-3(6//)-one derivatives (I) and related compounds showed good activity against gram-positive bacteria [Georgiadis, M.P.; Couladouros, E.A.; Delitheos, A. K. J. Pharm. Sci. 1992, 1126]. The derivatives of I are components of naturally occurring anthracycline antibiotics and many new synthetic derivatives of I have been reported exhibiting several biological activities. It was reported that the double bond of the compound I is essential for their antimicrobial activity [Georgiadis, M.P. J. Med .Chem. 1976, 19, 346]. It was also mentioned in the report [Georgiadis, M.P.; Couladouros, E.A.; Delitheos, A. K. J. Pharm. Sci 1992, 1126] that ether or ester functionality at C-l (at anomeric position) and bulky group at C-6 enhanced antimicrobial activity [Laliberte, R.; Medawar, G.; Lefebvre, Y. J. Med .Chem. 1973, 16, 1084]. In continuation of our endeavor to develop new anti-tubercular molecules we were interested to synthesize unsaturated C-3-alkyl and -arylalkyl 2,3-dideoxy glucopyranosides and investigate their ability to act as antitubercular agents due to some specific reasons: Firstly our group had earlier reported anti TB activity in acyclic deoxy monosaccharide derivatives prepared via Morita-Baylis-Hillman reaction between a,p-unsaturated sugar aldehydes and activated olefins [(a) Gupta, M. K.; Sagar, R.; Shaw, A.K.; Prabhakar, Y. S. Bioorg. Med. Ozew.2005, 13, 343. (b) Pathak, R.; Pant, C. S.; Shaw, A. K.; Bhaduri, A. P.; Gaikwad, A. N.; Sinha, S.; Srivastava, A.; Srivastava, K. K.; Chaturvedi, V.; Srivastava, R.; Srivastava, B. S. Bioorg. Med Chem. 2002, 10, 3187. (c) Pathak, R.; Shaw, A. K.; Bhaduri, A. P.; Chandrasekhar, K. V. G.; Srivastava, A.; Srivastava, K. K.; Chaturvedi, V.;Srivastava, R.; Srivastava, B. S.; Arora, S.; Sinha, S. Bioorg. Med. Chem. 2002,10,1695]. Secondly cyclic deoxy sugars are known to be biologically important compounds, being structural components of several antibiotics and other important naturally occurring molecules [Georgiadis, M.P. J. Med .Chem. 1976, 19, 346]. These sugar derivatives can be derived by replacing one hydroxyl group from common sugars with a hydrogen or non-0-linked functional group [Laliberte, R.; Medawar, G.; Lefebvre, Y. J. Med .Chem. 1973, 16, 1084]. Such a substitution brings a fundamental change in the chemical properties of the resulting sugar enhancing its thermodynamic stability and hydrophobicity. Thirdly our belief was further strengthened by the report of Elias. A. Couladouros et al that derivatives of 2//-pyran-3(6#)-one (I) having structure very similar to unsaturated C-3-alkyl and -arylalkyl 2,3-dideoxy glucopyranosides exhibit significant antibacterial, antifungal, anticoccidial, anti-inflammatory, and anticancer properties besides serving as intermediates in several natural product syntheses [Laliberte, R.; Medawar, G.; Lefebvre, Y..7. Med.Chem. 1973,16, 1084]. (FigureRemoved) Encouraged by the above literature report on antimicrobial properties of 2/f-pyran-3(6//)-one derivatives (I) and related compounds [(a)Georgiadis, M.P.; Couladouros, E.A.; Delitheos, A. K. J. Pharm. Sci 1992, 1126 , (b) Couladouros, E.A.; Strongilos, A.T. Angew. Chem., Int. Ed. Engl, 2002, 41, 3677] and the intriguing biological properdes of deoxysugars, we were prompted to develop the synthesis of C-3 branched enones derivatives of type I as antimycobacterial agents. Various synthetic methods have been reported for I and their derivatives [For the preparation of 2//-pyran-3(6//)-one derivatives (I) see references 1-9 in Georgiadis, M.P.; Couladouros, E.A.; Delitheos, A. K. J. Pharm. Sci. 1992, 1126]. However, based on the retro-synthetic scheme we identified deoxy enulosides 5a-c as a versatile synthetic intermediates to synthesize various molecules of the type I involving Morita-Baylis-Hillman chemistry [Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003,103, 811 & references cited therein]. In this endeavor we recently developed Morita-Baylis-Hillman chemistry of unsaturated C-3 branched deoxysugars [Sagar, R.; Pant, C. S.; Pathak, R.; Shaw, A. K. Tetrahedron 2004, 60, 11399] and now we wish to report herein the in vitro antimycobacterial activity of these deoxysugar derivatives. The unpublished compounds of the series 6a are different from the published compounds of the series in terms of the R group used while in the case of 6b series the unpublished compounds differ from the published compounds both in terms of the R group used and their stereochemistry at C-4. While all the published compounds of series 6b have threo configuration the unpublished compounds of series 6b have erythro configuration. The main objective of the present invention is to provide novel multifunctionalized unsaturated C-3-alkyl and - arylalkyl substituted 2,3-dideoxy glucopyranosides as anti-tubercular compounds. Another objective of the present invention is to provide novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides as promising anti-tubercular compounds which are better and have more potential for further exploitation, than most of the previously known anti-tubercular molecules, as they are derived from monosaccharides which are known for their easy availability as sources of metabolic energy, high tolerance [Fischer, J. F.; Harrison, A.W.; Bundy, G.L.; Wilkinson, K.F.; Rush, B.D.; Ruwart, M. J. J. Med. Chem. 1991, 34 , 4140], improved pharmacokinetics [Negre, E.; Chance, M. L.; Hanbuta, S. Y.; Monsigny, M.; Roche, A. C.; Mayer, R. M. Antimicrob. Agents Chemother. 1992, 35, 2228], better transport [Wolform, M. L.; Hanessian, S. J. Org. Chem. 1962, 27, 1800], low toxicity and their role in recognition phenomena many of which are of great pharmacological relevance [Cipolla, L.; Ferla, B. L.; Nicotra, F. Carbohydr. Polym. 1998, 37, 291], and therefore have greater compatibility to the human body (living system) and thus are very suitable candidates for the development of new drugs. Further these compounds being multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides derivatives are better from previously known anti-tubercular compounds because these novel molecules reported herein are deoxysugars, a distinct class of carbohydrates, which are thermally stable, hydrophobic in nature and play an important role in lipopolysaccharides, glycoproteins, and glycolipids, where they serve as ligands for cell-cell interactions or as targets for toxins, antibiotics and microorganisms and because of these properties they have received special attention during the last few decades. [Hallis, T. M; Liu, H-W. Ace. Chem. Res. 1999, 32, 579]. Lastly, as it is being taken into account nowadays that small molecules are more stable, more active and whose synthesis can be easily developed [Wong, C-H. Ace. Chem. Res. 1999, 32, 376] therefore, these novel class of antitubercular compounds being monosaccharide derivatives (small molecules) are better from previously known carbohydrate derived anti-tubercular molecules most of which are macromolecules like oligosaccharides (antibiotics) or part of other large molecules. The significance of these novel molecules reported in this invention as lead molecules for the development of a new anti-TB drug can very well be gauged from the above arguments. Another major objective of the present invention is to provide novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6a and 6b which show promising in vitro activity against M. tuberculosis /fj7/?v. Accordingly, the present invention provides novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides 6aa, 6ab, 6ac, 6ad, 6ae, 6af, 6ag, 6ah, 6ai, 6aj, 6ak, 6ba, 6bb, 6bc, 6bd, 6be, 6bf, 6bg, 6bh which show in-vitro activity against M. tuberculosis H3?RV in a MIC range of 50 jxg/ml to 1.56 (o,g/ml. The objective of the present invention is also to provide a process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6a and 6b, a new series of novel compounds useful as anti-tubercular agents. Accordingly, the present invention provides novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6a wherein R represents aryl groups selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group, while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by /?-nitrobenzoyl and different alkyl chlorides like tert-butyldimethylsilyl and tert-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl, In another embodiment of the present invention wherein the present invention provides a process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6a which involves the following steps : i) In another embodiment of the present invention wherein the reaction of 3,4,6-tri-O-acetyl-D-glucal of formula 1 with alcohols selected from the group consisting of methanol, propanol, isopropanol, butanol, isobutanol, sec-butanol, tert-butanol, pentanol, hexanol, heptanol, octanol, nonanol, decanol, sugar alcohols, all thioalcohols having upto ten carbons including substituted ones and thiol and variously substituted thiols in the presence of catalytic amount of la in an aprotic solvent viz tetrahydrofuron (THF) or by using lewis acids such as HfCU, ZrCU, BiCU, Cdla, Znk in solvents such as THF, dioxane, acetonitrile to furnish 2,3-dideoxy hex-2-enpyranoside derivative of formula 2. ii) In another embodiment of the present invention wherein the deacylation of formula 2 may be affected in methanol or ethanol with 2M sodium methoxide to obtain allylic alcohol of formula 3. This allylic alcohol can be isolated and purified by standard laboratory method such as column chromatography or crystallization, iii) In another embodiment of the present invention wherein the allylic oxidation of 3 is effected with oxidizing agents such as manganese dioxide (MnO2) in chloroform or dichloromethane solvent at room temperature or using Dess-Martin periodinane oxidation method to furnish 2,3-dideoxy hexenopyranoside-4-uloses of formula 4. These 2,3- dideoxy hexenopyranoside-4-uloses can be isolated and purified by standard laboratory method such as column chromatography. iv) In another embodiment of the present invention wherein the C-6 protection of 4 may be effected by using acetic anhydride with dry pyridine as solvent and dimetylaminopyridine (DMAP) as catalyst or by using acyl chlorides such as trimethylacetyl chloride, 4-nitrobenzoyl chloride in dry pyridine as solvent and dimetylaminopyridine (DMAP) as catalyst or using alkyl chlorides such as tert-butyl dimethyl silyl and tert-butyl diphenylsilyl chloride using dry dichloromethane as solvent or to furnish the compounds of formula 5 wherein R' represents the acetyl group, trimethyl acetyl group, p-nitrobenzoyl, ter/-butyl dimethyl silyl, tert-butyl diphenylsilyl respectively These protected 2,3-dideoxy hexenopyranoside-4-uloses of formula 5 can be purified by column chromatography. v) In another embodiment of the present invention wherein the formation of Baylis-Hillman adduct of general formula 6a may be effected by reacting various aliphatic and aromatic aldehydes with 5 to furnish the Morita-Baylis-Hillman adducts of formula 6a. The aliphatic aldehyde used may be selected from the group consisting of all aliphatic aldehydes having up to ten carbons and their amino, hydroxyl and keto substituted derivativatives, trihalomethylaldehyde such as chloral whereas aromatic aldehydes used may be selected from a the group consisting of all mono, di, tri, variously substituted benzaldehydes, all mono, di, tri, variously substituted aromatic heterocyclic aldehydes in the presence of lewis acids selected from the group consisting of TiCU, ZrCU, HfCLj, in different quantities and bases from the group consisting of TBAI, EtsN, PhsP, (Me)2S or lewis acids selected from the group consisting of ZnI2, Cdb, Cuh in different quantities in dry solvents from the group consisting of dichloromethane, chloroform, dioxane, tetrahydrofuran and acetonitrile in a temperature range of-78°C to 150°C. In another embodiment of the present invention wherein the present invention provides novel multi-functionalized unsaturated C-3-alkyl and -arylalkyl substituted erythro 2,3-dideoxy glucopyranosides of general formula 6b wherein R represents aryl groups selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group, while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by ;?-nitrobenzoyl and different alkyl chlorides like tert-butyldimethylsilyl and tert-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars and OR" as a whole represents thiol and all substituted thiols. In another embodiment of the present invention wherein the present invention provides a process for stereoselective reduction of C-4 keto group of unsaturated C-3 -alkyl and -arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6a by stirring them in solvents selected from the group consisting of methanol and ethanol using reducing agents selected from the group consisting of sodium borohydride, sodium triacetoxyborohydride and sodium cyanoborohydride in different quantities in the presence of CeCh.TFkO in different quantities for 1-3 h to furnish the erythro derivative of C-3-alkyl and -arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6b in good yield. These erythro derivatives of general formula 6b can be isolated and purified by standard laboratory method such as column chromatography. Accordingly the present invention also provides a pharmaceutical composition comprising therapeutically effective amount of compound of general formula 6 optionally along with pharmaceutically acceptable carriers, diluents and exciepients. In an embodiment of the invention wherein the composition is useful for the treatment of tuberculosis. The compounds 1-5 are known in the literarature and are prepared by known methods a). Pre'vost, N.; Rouessac, F. Synth. Commun. 1997,27, 2325-2335. b). Sagar, R.; Pant, C. S.; Pathak, R.; Shaw, A. K. Tetrahedron 2004, 60, 11399-11406 Water soluble derivatives of compounds of series 6a and 6b may be prepared by incorporation of the polar amino group and their salts in the form of hydrochloride or sulphate, or other polar groups such as amide and acid groups etc, into the molecules of the aforesaid series. The invention is further illustrated by the following examples which should not however be construed to limit the scope of the present invention. EXAMPLE I Isopropyl-6-0-trimethyIacetyI-3-[hydroxy (4-cyanophenyl) methyI]-2,3-dideoxy-a-D-g/Vc^ro-hex-2-enopyranoside-4-ulose (Compound 6aa) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CF^C^ (5 mL) at -78°C was added TiCU (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, trimethylacetyl (pivaloyl) protected enuloside 5a (1.0 mmol) and 4-cyanobenzaldehyde (2.0 mmol) in dry CP^Ch (5 mL) was added to the reaction mixture. The reaction mixture was slowly warmed to -30°C and stirred for 48 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6aa as oil [94%]. Example II Isopropyl-6-O-trimethylacetyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-^(vcero-hex-2-eno pyranoside-4-ulose (Compound 6ab) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2Cl2 (5 mL) at -78°C was added TiCU (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, trimetylacetyl (pivaloyl) protected enuloside 5a (1.0 mmol) and decanal (2.0 mmol) in dry CH2C12 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for SOhrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ab as oil [81%]. Example III Isopropyl-6-0-trimethylacetyl-3- [hydroxy (3-nitrophenyl) methyl] -2,3-dideoxy-a-D-g(ycer0-hex-2-enopyranoside-4-ulose (Compound 6ac) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCL* (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, trimetylacetyl (pivaloyl) protected enuloside 5a (1.0 mmol) and 3-nitrobenzaldehyde (2.0 mmol) in dry CH2C12 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 10 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ac as oil [64%]. Example IV Isopropyl-6-0-trimethylacetyI-3-[hydroxy (4-trifluoromethylphenyl) methyl]-2,3-dideoxy-a-D-£(ycm>-hex-2-enopyranoside-4-ulose (Compound 6ad) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, trimetylacetyl (pivaloyl) protected enuloside 5a (1.0 mmol) and 4-trifluromethylbenzaldehyde (2.0 mmol) in dry CH2C12 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 10 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ad as oil [86%]. Example V Isopropyl-6-0-4-nitrobenzoyI-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-£/ycero-hex-2-enopyranoside-4-ulose (Compound 6ae) To a stirred solution of tetrabutylammonium iodide, THAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and 4-nitrobenzaldehyde (2.0 mmol) in dry CH2Cl2 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 6 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ae as oil [88%]. Example VI Isopropyl-6-0-4-nitrobenzoyl-3-[hydroxy (4-trifluromethyl phenyl) methyl]-2,3-dideoxy-a-D-£(ycer0-hex-2-enopyranoside-4-ulose (Compound 6af) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2Cl2 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and 4-trifluromethylbenzaldehyde (2.0 mmol) in dry CHbCh (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 11 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6af as oil [86%]. Example VII Isopropyl-6-0-4-nitrobenzoyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-#/jcer0-hex-2-enopyranoside-4-ulose (Compound 6ag) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCLj (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and decanal (2.0 mmol) in dry CHaC^ (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 33 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ag as oil [87%]. Example VIII Isopropyl-6-0-4-nitrobenzoyl-3- [hydroxy (4-cyanophenyl) methyl] -2,3-dideoxy-a-D-£/ycer0-hex-2-enopyranoside-4-ulose (Compound 6ah) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry Cf^Ck (5 mL) at -78°C was added TiCU (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and 4-cyanobenzaldehyde (2.0 mmol) in dry CHaCb (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 7 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ah as oil [86%]. Example IX Isopropyl-6-0-4-nitrobenzoyl-3-[hydroxy (4-fluorophenyl) methyl]-2,3-dideoxy-a-D-£(ycer0-hex-2-enopyranoside-4-ulose (Compound 6ai) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and 4-flurobenzaldehyde (2.0 mmol) in dry CH2Cl2 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 21 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ai as oil [70%]. Example X Isopropyl-6-0-4-nitrobenzoylO-(l-hydroxybutyl)-23-dideoxy-a-D-£/ycm>-hex-2-enopyranoside-4-ulose (Compound 6aj) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCU (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and butanal (2.0 mmol) in dry CH2C12 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 24 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6aj as oil [84%]. Example XI Isopropyl-6-0-acetyl-3-[hydroxy (4-nitrophenyl) methyl] -2,3-dideoxy-o>D-g(ycer0-hex -2-enopyranoside-4-ulose (Compound 6ak) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, acetyl protected enuloside 5c (1.0 mmol) and 4-nitrobenzaldehyde (2.0 mmol) in dry CHaCb (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for 5 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ak as oil [64%]. Example XII Isopropyl-6-6Mrimethylacetyl-3-[hydroxy (4-cyanophenyl) methyl]-2,3-dideoxy-a-D-erythro-he\-2-enopyranoside (Compound 6ba) To a stirred solution of the compound 6aa in ethanol (10ml), NaBtLt (0.5 mmol) and CeCls.TtbO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 5h. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6ba in 75% yield. Example XIII Isopropyl-6-O-trimethylacetyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-erv//iro-hex-2-enopyranoside (Compound 6bb). To a stirred solution of the compound 6ab in ethanol (10ml), NaBRt (0.5 mmol) and CeCla.THaO (1.0 mmol) were added and the reaction mixture'was stirred continuously at room temperature for the 5hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bb in 68% yield. Example XIV Isopropyl-6-0-trimethylacetyl-3-[hydroxy (3-nitrophenyl) methyI]-2,3-dideoxy-o-D-erythro-hex-2-enopyranoside (Compound 6bc). To a stirred solution of the compound 6ac in ethanol (10ml), NaBH4 (0.5 mmol) and CeCls.THaO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 3hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bc in 90% yield. Example XV Isopropyl-6-6Mrimethylacetyl-3-[hydroxy (4-trifluoromethylphenyl) methyl]-2,3-dideoxy-a-D-£ryfAro-hex-2-enopyranoside (Compound 6bd). To a stirred solution of the compound 6ad in ethanol (10ml), NaBH4 (0.5 mmol) and CeCla.TFhO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 4hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bd in 80 % yield. Example XVI Isopropyl-6-0-4-nitrobenzoyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-eryfAro-hex-2-enopyranoside (Compound 6be). To a stirred solution of the compound 6ae in ethanol (10ml), NaBRj (0.5 mmol) and CeCls.ytbO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 6hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6be in 75% yield. Example XVII IsopropyI-6-0-4-nitrobenzoyl-3-[hydroxy (4-trifluromethyl phenyl) methyl]-2,3-dideoxy-a-D-erv^ro-hex-2-enopyranoside (Compound 6bf). To a stirred solution of the compound 6af in ethanol (10ml), NaBPL; (0.5 mmol) and (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 3hrs. After completion of the reaction (TLC control), excess NaBPLt was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bf in 80%yield. Example XVIII Isopropyl-6-6M-nitrobenzoyl-3-(l-hydroxydecyl)-23-dideoxy-a-D-eiyfAr0-hex-2-enopyranoside (Compound 6bg). To a stirred solution of the compound 6ag in ethanol (10ml), NaBH4 (0.5 mmol) and CeCl3.7H2O (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 6 hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bg in 87% yield. Example XIX Isopropyl-6-0-acetyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideo\y-a-D-erythro-hex -2-enopyranoside (Compound 6bh). To a stirred solution of the compound 6ak in ethanol (10ml), NaBtLt (0.5 mmol) and CeCb.THaO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 2h. After completion of the reaction (TLC control), excess NaBHU was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bh in 73 % yield. ADVANTAGES i) All the compounds of series 6a and 6b reported in this invention are novel. They have been reported for the first time. ii) The compounds of series 6a and 6b reported in this invention have been reported to show anti-TB activity for the first time. The compounds 6aa, 6ab, 6ac, 6ad, 6ae, 6af, 6ag, 6ah, 6ai, 6aj, 6ak, 6ba, 6bb, 6bc, 6bd, 6be, 6bf, 6bg, 6bh have been reported to show in-vitro activity against M. tuberculosis //37^?v in a MIC range of 50 ng/ml to 1.56 ug/ml. iii) The most active compounds of series 6a and 6b reported in this invention showed little or no cytotoxicity on being tested on VERO cell line. iv) The novel compounds of series 6a and 6b are promising anti-tubercular compounds which are better and have more potential for further exploitation, than most of the previously known anti-tubercular molecules, as they are derived from monosaccharides which are known for their easy availability as sources of metabolic energy, high tolerance improved pharmacokinetics, better transport, low toxicity and their role in recognition phenomena many of which are of great pharmacological relevance, and therefore have greater compatibility to the human body (living system) and thus are very suitable candidates for the development of new drugs. Further these compounds being multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides derivatives are better from previously known anti-tubercular compounds because these are deoxysugars. Deoxysugars a distinct class of carbohydrates, which are thermally stable, hydrophobic in nature and play an important role in lipopolysaccharides, glycoproteins, and glycolipids, where they serve as ligands for cell-cell interactions or as targets for toxins, antibiotics and microorganisms and because of these properties they have received special attention during the last few decades. Lastly, as it is being taken into account nowadays that small molecules are more stable, more active and their synthesis can be easily developed therefore, these novel class of antitubercular compounds being monosaccharide derivatives (small molecules) are better from previously known carbohydrate derived anti-tubercular molecules most of which are macromolecules like oligosaccharides (antibiotics) or part of other large molecules. The significance of these novel molecules reported in this invention as lead molecules for the development of a new anti-TB drug can very well be gauged from the above arguments. v) All the compounds of series 6a and 6b reported in this invention have been prepared by reacting protected 2,3-dideoxy hexenopyranoside-4-uloses of formula 5 with different aldehydes using Morita-Baylis-Hillman chemistry. Morita-Baylis Hillman (MBH) chemistry has been recognized as one of the most versatile and more economically feasible C-C bond forming reactions to generate multifunctionalized allylic alcohols generally called MBH or BH adducts. Use of this methodology thus provides a most versatile and economically viable route for the preparation of a large number of BH adducts of 6a series using different aldehydes and their reduced forms (6b series). vi) The compounds of series 6a and 6b were prepared using easily available, inexpensive and benign reagents like TiCU and TBAI in dichloromethane. vii) Taking into consideration points (i) to (vi) leads to the conclusion that the novel series of compounds 6a and 6b provide a new, most promising lead for the development of a potent new anti -TB drug. This importance of this invention lies in the fact that it provides a new, entirely different lead for the development of a potent new anti -TB drug based upon monosaccharide derived 2-deoxy sugar opening up a new, promising, hitherto unexplored chapter in the race for the development of a badly needed potent new anti-TB drug. ANTITUBERCULAR ACTIVITY Agar dilution method Briefly, 2-fold serial dilutions of each test compound/drug were incorporated into 7H10 agar. Inoculum of M. tuberculosis H37Rv was prepared from fresh Lowenstein-Jensen slants adjusted to 1 mg/mL (wet weight) in Tween 80 (0.05%) saline and diluted to 10"2 to give a concentration of approximately 107 cfu/mL. 5 mL of bacterial suspension was spotted into 7H10 agar tubes containing 2-fold serial dilution of drugs per mL. The tubes were incubated at 37°C and final readings were recorded after 30 days. The MICs were read as the minimum concentration of drugs/compounds that completely inhibited the growth of M tuberculosis per spot. Ofloxacin was used as the standard drug. Microwell plate alamar blue assay (MABA) Antimycobacterial activity was determined by Microwell plate based Alamar blue assay (MABA) using M. tuberculosis H37Ra as a surrogate for the virulent H37Rv strain. The results of MABA have been found comparable to the standard agar dilution system based assay. The standard antitubercular drugs Rifamycin, Isoniazid, p-Amino salicylic acid, Ethambutol and Ethionamide (MIC range 3 Drug susceptibility testing by BACTEC radiometric susceptibility assay: The assay was done using M. tuberculosis H37Rv as test stain. The assay grows M tuberculosis in 7H12 medium containing 14C labeled palmitic acid as substrate and 14CC>2 is produced. The amount of I4CC>2 detected reflects the rate and amount of growth occurring in the vial and is expressed in term of the "Growth Index" (GI). On addition of an antitubercular drug to the medium suppression of growth of the test organism M tuberculosis can be detected by either a decline or very small increase of the daily GI output as compared to the control. Streptomycin (6ug/ml) and Rifampin (2ug/ml) were used as positive control. All compounds showing MIC below 25(j,g/ml in agar tube dilution were confirmed for activity against M. tuberculosis HjyRv by BACTEC radiometric assay. Cytotoxicity studies The most active compounds 6aa, 6ab, 6bb and 6ak were tested for their cytotoxicity in VERO cell line. VERO cells originally obtained from ATCC and maintained in CDRI, were seeded on a 96 well plate and incubated at 37°C in 5% CC^ and 95% air. Cells were exposed to varying concentrations (25, 50, 100 ug/ml) of the compound for 72 hours. MTT assay was performed as per the standard protocol to assess cell viability. Triplicates of each assay were carried out. 6ab, 6bb and 6ak were found to be cytotoxic at 25 ug/ml while 6aa showed no cytotoxicity at the dose of 100 ug/ml. Cytotoxicity was also observed for mouse macrophage cell line J 744A.I which is an important cell line for M tuberculosis infection has been used for the assay. The assay is based on the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] reduction. The drug concentrations used for the assay were 50, 25 and 12.5 ug/ml, in parallel with known toxic compounds and standard antimycobacterial drugs like Rifampicin and Sparfloxacin. The cell death was significantly lower (8-10-fold) than the toxic compound and very similar to standard drugs. Tablel. Antimycobacterial activity against M. tuberculosis H^RV by agar dilution (TableRemoved) WE CLAIM 1) A novel multifunctionalized unsaturated C-3-alkyl or arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6 Wherein R represents aryl group selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group, while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by p-nitrobenzoyl and different alkyl chlorides like tert-butyldimethylsilyl and terf-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars and OR" as a whole represents thiol and all substituted thiols , pharmaceutically acceptable salts and derivatives therof. (Formula removed) 2) A compound as claimed in claim (1) of the structure of general formula 6 wherein the structure of the 4-keto compound is as follows formula removed i) wherein R represents aryl groups selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group, ii) R' represents hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by p-nitrobenzoyl and different alkyl chlorides like terr-butyl dimethyl silyl and tert-butyl diphenylsilyl chloride, iii) R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars, iv) OR" as a whole represents thiol and all substituted thiols, 3) A compound as claimed in claim 1 wherein the structure of the 4-erythro derivative of general formula 6a compound is as follows: i) wherein R represents aryl groups selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group. ii) R' represents hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by p-nitrobenzoyl and different alkyl chlorides like ter/-butyl dimethyl silyl and tert-butyl diphenylsilyl chloride, iii) R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars, iv) OR" as a whole represents thiol and all substituted thiols. 4) The compound as claimed in claim 1 wherein the representative compounds of general formula 6a and 6b are given below: i) Isopropyl-6-0-trimethylacetyl-3-[hydroxy (4-cyanophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6aa) ii) Isopropyl-6-O-trimethylacetyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ab) iii) Isopropyl-6-0-trimethylacetyl-3-[hydroxy (3-nitrophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ac) iv) Isopropyl-6-0-trimethylacetyl-3-[hydroxy (4-trifluoromethylphenyl) methyl]-2,3-dide oxy- v) Isopropyl-6-0-4-nitrobenzoyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose(6ae) vi) Isopropyl-6-O-4-nitrobenzoyl-3-[hydroxy (4-trifluromethyl phenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6af) vii) Isopropyl-6-O-4-nitrobenzoyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ag) viii) Isopropyl-6-O-4-nitrobenzoyl-3-[hydroxy (4-cyanophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ah) ix) Isopropyl-6-O-4-nitrobenzoyl-3-[hydroxy (4-fluorophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ai) x) Isopropyl-6-O-4-nitrobenzoyl-3-(l-hydroxybutyl)-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6aj) xi) Isopropyl-6-Oacetyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-g/vcero-hex-2-enopyranoside-4-ulose (6ak) xii) Isopropyl-6-0-trimethylacetyl-3-[hydroxy (4-cyanophenyl) methyl]-2,3-dideoxy-a-D- erythro-hex-2-enopyranoside (6ba). xiii) Isopropyl-6-O-trimethyl acetyl-3-(l-hydroxy decyl)-2,3-dideoxy-a-D-erytfzro-hex- 2-enopyranoside (6bb). xiv) Isopropyl-6-(9-trimethylacetyl-3-[hydroxy (3-nitrophenyl) methyl]-2,3-dideoxy-a-D- ery^ro-hex-2-enopyranoside (6bc). xv) Isopropyl-6-O-trimethylacetyl-3-[hydroxy (4-trifluoromethylphenyl) methyl]-2,3- dideoxy-a-D-er>tf/zr0-hex-2-enopyranoside(6bd). xvi) Isopropyl-6-O4-nitrobenzoyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D- ery//zro-hex-2-enopyranoside(6be). xvii) Isopropyl-6-O4-nitrobenzoyl-3-[hydroxy (4-trifluromethyl phenyl) methyl]-2,3- dideoxy-a-D-ery//zro-hex-2-enopyranoside6bf). xviii) Isopropyl-6-O-4-nitrobenzoyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-ery^/zro-hex-2- enopyranoside (6bg). xix) Isopropyl-6-0-acetyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-erythro- hex-2-enopyranoside (6bh). 5) A novel compound as claimed in claim 1 wherein the novel compounds of series 6a and 6b showed anti-tubercular activity for the first time. 6) A novel compound as claimed in claim 1 wherein the novel compounds of series 6a and 6b showed activity for the first time against the strain of mycobacterium tuberculi H37Ra. 7) A novel compound as claimed in claim 1 wherein the novel compounds of series 6a and 6b showed activity for the first time against the strain mycobacterium tuberculi 8) A process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6 as claimed in claim 1 comprising the following steps : i) providing the compound of formula 5 by known methods followed by formation of Baylis-Hillman adduct of general formula 6 by reacting compound of formula 5 with aliphatic or aromatic aldehydes in the presence of a lewis acid and a base in a chlorinated aprotic solvent or non-chlorinated aprotic solvent at a temperature ranging between -78 °C to 150 °C to furnish the Morita-Baylis-Hillman adducts of formula 6a, ii) stereoselective reduction of C-4 keto group of unsaturated C-3-alkyl and -arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6a obtained in step (v) by stirring in polar protic solvent using reducing agent optionally in presence of CeCls for 1-7 hr to furnish the erythro derivative of C-3-alkyl or arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6b, isolating and purifying by standard laboratory method such as column chromatography. 9) A process as claimed in claim (8) wherein the base used in step (i) is selected from the group consisting of pyridine, triethylamine. (10) A process as claimed in claim (8) wherein the solvent used in step (i) is selected from aprotic chlorinated solvents from the group consisting of chloroform dichloromethane, 1,2-dichloroethane. (11) A process as claimed in claim (8) wherein the aldehyde used in step (i) is selected from the group consisting of aliphatic aldehydes such as all aliphatic aldehydes having upto ten carbons and their amino, hydroxyl and keto substituted derivatives, trihalomethylaldehyde such as chloral etc. or from a group consisting of aromatic aldehydes such as all mono, di, tri, variously substituted benzaldehydes, all mono, di, tri, variously substituted aromatic heterocyclic aldehydes. (12) A process as claimed in claim (8) wherein the lewis acid used in step (i) is selected from the group consisting of TiCU, ZrCU, HfCU, Zn, Cdla, Cul2. (13) A process as claimed in claim (8) wherein the base used in step (i) is selected from the group consisting of TBAI, triethylamine, triphenylphosphine, dimethyl sulfide . (14) A process as claimed in claim (8) wherein the solvent used in step (i) is selected from chlorinated aprotic solvents from the group consisting of, dichloromethane, 1,2- dichloroethane , chloroform, etc. or non-chlorinated aprotic solvents selected from the group consisting of THF, acetonitrile, dioxane, diethylether. 15) A process as claimed in claim (8) wherein the reducing agent used is selected from the group consisting of sodium borohydride, sodium cyanoborohydride, sodium triacetoxy borohydride. (16) A process as claimed in claim (8) wherein the solvent used in step (ii) is selected from polar protic solvents from the group consisting of methanol, ethanol, 1,2-etanediol etc. 17. A process as claimed in claim (8) wherein the Water soluble derivatives of compounds of series 6a and fib may be prepared by incorporation of the polar amino group and their salts in the form of hydrochloride or sulphate, or other polar groups such as.amide and acid groups etc. into the molecules . 17) Use of novel compounds of general formula 6a and 6b as claimed in claim (1) for the treatment of Tuberculosis. 18) Use of novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6a and their reduced derivatives having general formula fib as claimed in claim (7) wherein the MIC value of the representative compounds fiaa, 6ab, fiac, fiad, 6ae, fiaf, fiag, fiah, fiai, fiaj, fiak, fiba, fibb, 6bc, fibd, fibe, fibf, fibg, fibh are in a range of 50 ug/ml to 1.56 ug/ml. 24) Use as claimed in claim 22 wherein in vitro activity against M. tuberculosis Hi7Rv shown by the representative compounds fiaa, fiab, fiac, fiad, fiae, fiaf, fiag, fiah, fiai, fiaj, fiak, fiba, fibb, fibc, fibd, fibe, fibf, fibg, fibh are in a MIC range of 50 ng/ml to 1.56 ug/ml. 19) Use as claimed in claim 17 wherein in vitro and in vivo activity against M. tuberculosis //37/?v shown by any of the novel compounds claimed in claim (1), (2), (3) and"(4). 20) Use as claimed in claim 17 wherein the most active compounds of the novel series of compounds of general formula 6a and fib reported in this invention showed little or no. cytotoxicity on being tested on VERO cell line. 21) A Pharmaceutical composition comprising therapeutically effective amount of compound of general formula 6 22) Wherein R represents aryl group selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group, while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by j9-nitrobenzoyl and different alkyl chlorides like tert-butyldimethylsilyl and tert-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars and OR" as a whole represents thiol and all substituted thiols optionally along with pharmaceutically acceptable carriers, diluents and exciepients. 22) A Novel multifunctionalized unsaturated C-3-alkyl or -arylalkyl substituted 2,3-dideoxy glucopyranosides substantially as herein described with reference to the examples and drawings accompanying the specification.

Full Text

The present invention relates to a novel series of anti-tubercular multifunctionalized unsaturated C-3-alkyl or arylalkyl substituted 2,3-dideoxy glucopyranosides having general formula 6a and 6b respectively
(FigureRemoved)

wherein R represents aryl groups selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group , while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by p-nitrobenzoyl and different alkyl chlorides like ter/-butyldimethylsilyl and terf-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars and OR" as a whole represents thiol and all substituted thiols. The present invention also relates to a process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and - arylalkyl substituted 2,3-dideoxy glucopyranosides.
This invention particularly relates to a process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and - arylalkyl substituted 2,3-dideoxy glucopyranosides, a new series of anti-tubercular agents.
These unsaturated 2,3-dideoxy glucopyranosides of general formula 6a and 6b are new chemical compounds and they had not been prepared earlier.
More specifically the present invention provides a process for the preparation of novel
series of multifunctionalized unsaturated C-3-alkyl and - arylalkyl substituted 2,3-
dideoxy glucopyranosides of general formula 6a and 6b.
These unsaturated C-3-alkyl and - arylalkyl substituted 2,3-dideoxy glucopyranosides are
novel compounds and are useful as anti-tubercular agents. These compounds have been
tested against M. tuberculosis H37RV by agar dilution method and some of these
compounds have shown promising anti-tubercular activity. The invention thus relates to
the pharmaceutical industry.
Several of these novel compounds are showing promising anti-tubercular activity against
M. tuberculosis //j/^by agar dilution method.
Background of the present invention
Tuberculosis (TB), a chronic bacterial infection is a leading cause of death worldwide, from a single infectious agent [(a) Dolin, P. J.; Raviglione, M. C.; Kochi, A. Bull. WHO 1994, 72, 213; (b) Huebner, R. E.; Castro, K. G. Ann. Rev. Med. 1995, 46, 47]. TB is caused by mycobacterium of the 'tuberculosis complex', including M. bovis, M. affricanum but mainly by M. tuberculosis [Pasqualoto, K. F. M.; Ferreira, E. I. Current Drug Target 2001, 2, 427]. According to WHO estimates roughly one-third of the world's population is latently infected with the tuberculosis bacteria [Farmer, P.; Bayona, J.; Becerra, M.; Furin, J.; Henry, C.; Hiatt, H.; Kim, J. Y.; Mitnick, C.; Nardell, E.; Shin, S. Int. J. Tuberc. LungDis. 1998, 2, 869].
It is a worse killer than malaria and AIDS combined. It is estimated that by 2020 A.D. nearly one billion more people will be infected, 200 million people will get sick and 70 million will die from tuberculosis if proper steps to control it are not taken. [ (a) Daffe, M.; Draper, P. Adv. Microb. Physiol 1998,39,131; (b) WHO Global tuberculosis programme- Tuberculosis Fact Sheet, 1998. (http://www.who.int/gtb/publication/index. htm#Report)].
In all, there are approximately 70 species in the genus Mycobacterium, many of which are opportunistic pathogens in humans and animals, while others like M. avium are
emerging pathogens most notably in AIDS patients [Iran, T.; Saheba, E.; Arcerio, A.V.; Chavez, V.;Li, Q.; Martinez, L.E; Primm, T.P. Bioorg. Med. Chem. 2004,12,4809.].
The AIDS pandemic has had a big impact on worldwide TB prevalence. One-third of the increase in the incidences of the TB in the last 5 years can be attributed to co-infection with HIV [Rattan, A.; Kalia, A. and Ahmad, N. Emerg. Infect. Dis. 1998, 4, 195].The other factor responsible for increase in TB cases is the emergence of the so called MDR-TB, resistant to some or all currently known TB drugs. Emergence of MDR-TB is a result of lack of patient's compliance with long term chemotherapy, prescription of wrong drugs or wrong combination of drugs by doctors and health workers, unreliable drug supply, delay in diagnosis, variable efficacy of BCG vaccines and various other factors such as unavailability of drugs in remote areas of certain high risk regions, [(a) WHO Global tuberculosis programme- Tuberculosis Fact Sheet, 1998. [http://www.who.int/gtb/publication/index. htm#Report]. (b) WHO - Country Profiles: Brazil. Annual Report, 1997. [http://www.who.int]. (c) Rattan, A.; Kalia, A. and Ahmad, N. Emerg. Infect. Dis. 1998,4, 195. (d) Chopra, P., Meena, I. S., Singh, Y. Indian J. Med. ^-.,2003,7,117].
MDR-TB is becoming increasingly difficult and expensive to treat with an ever rising mortality rate that raises the specter that TB will once again become an incurable disease [Pathak, A. K.; Pathak, V.; Maddry, J. A.; Suling, W. J.;Gurcha, S. S.; Besra, G. S.; Reynolds, R. C. Bioorg. Med.Chem. 2001,9, 3145]. Current strategy for treatment of TB involves use of front line drugs like INH, rifampin, PZA and ethambutol for two months followed by four months of follow up treatment with INH and rifampin [Bass, J. B., Jr.; Farer, L. S.; Hopewell, P.C.; O'Brien, R.; Jacobs, R. F.; Ruben, F.; Snider, D. E., Jr.; Thornton, G., the American Thoracic Society. Am. J. Respir. Crit. Care Med. 1994,149, 1359]. However this combination therapy is not always successful in case of MDR suspected patients. The latest anti-TB drug was introduced almost 30 years ago when the problem of MDR-TB and co-infection with HIV did not exist and thus to effectively combat these problems there is an urgent need for development of new anti TB drugs that have unique mechanisms of action from presently used anti-tubercular drugs with improved properties such as enhanced activity against MDR strains [(a) Pathak, A. K.; Pathak, V.; Seitz, L.; Maddry, J. A.;Gurcha, S. S.; Besra, G. S.; Suling, W. J.; Reynolds,
R. C.Bioorg. Med. Chem. 2001, P, 3129.(b) Pathak, A. K.; Pathak, V.; Maddry, J. A.; Suling, W. J.; Gurcha, S. S.; Besra, G. S.; Reynolds, R. C. Bioorg. Med. Chem. 2001, 9, 3145.(14) (c) C.A. no. 90: 152534y Wojtowicz, M; Wienlawski, W.Acta Pol. Pharm. 1978, 35, 37. (d) C.A. no. 89: 110253e Wojtowicz, M.; Wienlawski, W. Acta Pol. Pharm. 1977, 34, 575]. These molecules should be effective against latent TB, should have shortened duration of therapy thereby reducing chances of non-compliance of patients and should also ideally have reduced toxicity, rapid mycobactericidal mechanism of action and the ability to penetrate host cells and exert anti-mycobacterial effects in the intra cellular environments [Panda, G.; Siddiqui, S.; Mishra, J. K.; Chaturvedi, V.; Srivastava, A. K.; Srivastava, R.; Srivastava, B. Bioorg. Med. Chem. 2004,12, 5629].
The recent report [Cole, S.T.; Brosch, R.; Parkhill, J.; et al. Nature 1998, 393, 537] on complete genome sequence of Mycobacterium tuberculosis has provided a more rational and directional approach to the search for new drug targets. In general, gene products involved in mycobacterial metabolism, persistence, transcription, synthesis of cell-wall and virulence would be possible targets for the new drug development [Chopra, P., Meena, I. S., Singh, Y. Indian J. Med. Res., 2003,1,117].
The intrinsic resistance of the TB bacilli to antibiotics and chemotherapeutic agents can be ascribed to its unique and intricate cell wall structure which is made up of polysaccharides, proteins and lipids [Khasnobis, S.; Escuyer, V. E.; Chatterjee, D. Espert Opin.Ther. Targets 2002, 6,21].
The sugar components in these polysaccharides have been identified as L-rhamnose, D-arabinofuranose and D-galactofuranose which have no role in mammalian metabolism [Lee, R.E.; Smith, M.D.; Pickering, L.; Fleet, G.W. Tetrahedron Lett. 1999, 40, 8689] thus making the biochemistry and attendant enzyme pathways ideal targets for the development of new,potent and selective antimycobacterial agents [Pathak, A. K.; Pathak, V.; Maddry, J. A.; Suling, W. J.; Gurcha, S. S.; Besra, G. S.; Reynolds, R. C. Bioorg. Med. Chem. 2001, P, 3145].
Due to the easy availability of carbohydrates as sources of metabolic energy, their high tolerance [Fischer, J. F.; Harrison, A.W.; Bundy, G.L.; Wilkinson, K.F.; Rush, B.D.; Ruwart, M. J. J. Med. Chem. 1991, 34 , 4140], improved pharmacokinetics [Negre, E.;

Chance, M. L.; Hanbuta, S. Y.; Monsigny, M.; Roche, A. C.; Mayer, R. M. Antimicrob. Agents Chemother. 1992, 35, 2228], better transport [Wolform, M. L.; Hanessian, S. J. Org. Chem. 1962, 27, 1800], low toxicity and their role in recognition phenomena many of which are of great pharmacological relevance [Cipolla, L.; Ferla, B. L.; Nicotra, F. Carbohydr. Polym. 1998, 37, 291], much effort is being focused towards the development of carbohydrate-based therapeutics during the last few years [McAuliffe, J.; Hindsgaul, 0. Chemistry and Industry 1997, 170]. However, current efforts are mainly directed towards the development of small molecules which are more stable, more active and whose synthesis can be easily developed [Wong, C-H. Acc.Chem. Res. 1999, 32, 376]. Certain sugar derivatives and glucofuranose analogues have been reported as antitubercular agents recently [(a) Tripathi, R.P.; Tewari, N.; Dwivedi, N.; tewari, V. K. Medicinal Research Reviews 2005, 25, 93. (b) Maddry, J. A.; Bansal, N.; Bermudez, L. E.; Comber, R.N.; Orme, W. J.; Suling, W. J.; Wilson, L. N.; Raynolds, R. C. Bioorg. Med. Chem. Lett. 1998, 8, 237. (c) John, T.B.; Varalakshmi, D.; Todd, S.; Takayama, K.; Patrick, J. B.; Besra, G.S. Science 1997, 39, 1420. (d) Chung, G. A.; Aktar, Z.; Jackson, S.; Duncan, K. Antimicrob. Agents Chemother. 1995,39,2235. (e) Namane, M.; Goujette, C.; Pillion, M.P.; Pillion, J.; Huynh, T.; Dinh, J. J. Med. Chem. 1992, 35, 3039]. During the past decades, deoxysugars, a distinct class of carbohydrates, have received special attention due to their thermal stability, hydrophobicity and important role in lipopolysaccharides, glycoproteins, and glycolipids, where they serve as ligands for cell-cell interactions or as targets for toxins, antibiotics and microorganisms [Hallis, T. M.; Liu, H-W. Ace Chem.Res. 1999,32,579].
In our ongoing programme on the search of new anti-tubercular agents we have been focusing our efforts on the synthesis of easily available monosaccharide derived anti-tubercular agents [(a) Gupta, M. K.; Sagar, R.; Shaw, A.K.; Prabhakar, Y. S. Bioorg. Med.Chem.2005,13,343. (b) Pathak, R.; Pant, C. S.; Shaw, A. K.; Bhaduri, A. P.; Gaikwad, A. N.; Sinha, S.; Srivastava, A.; Srivastava, K. K.; Chaturvedi, V.; Srivastava, R.; Srivastava, B. S. Bioorg. Med. Chem.20Q2, 10, 3187. (c) Pathak, R.; Shaw, A. K.; Bhaduri, A. P.; Chandrasekhar,K. V. G.; Srivastava, A.; Srivastava, K. K.; Chaturvedi, V.;Srivastava, R.; Srivastava, B. S.; Arora, S.; Sinha, S. Bioorg. Med.Chem.2W2,l 0,1695].
These molecules are chain extended acyclic or cyclic deoxysugar derivatives. We found from the literature survey on antimicrobial activity of cyclic deoxysugars that 2//-pyran-3(6//)-one derivatives (I) and related compounds showed good activity against gram-positive bacteria [Georgiadis, M.P.; Couladouros, E.A.; Delitheos, A. K. J. Pharm. Sci. 1992, 1126]. The derivatives of I are components of naturally occurring anthracycline antibiotics and many new synthetic derivatives of I have been reported exhibiting several biological activities. It was reported that the double bond of the compound I is essential for their antimicrobial activity [Georgiadis, M.P. J. Med .Chem. 1976, 19, 346]. It was also mentioned in the report [Georgiadis, M.P.; Couladouros, E.A.; Delitheos, A. K. J. Pharm. Sci 1992, 1126] that ether or ester functionality at C-l (at anomeric position) and bulky group at C-6 enhanced antimicrobial activity [Laliberte, R.; Medawar, G.; Lefebvre, Y. J. Med .Chem. 1973, 16, 1084]. In continuation of our endeavor to develop new anti-tubercular molecules we were interested to synthesize unsaturated C-3-alkyl and -arylalkyl 2,3-dideoxy glucopyranosides and investigate their ability to act as antitubercular agents due to some specific reasons:
Firstly our group had earlier reported anti TB activity in acyclic deoxy monosaccharide derivatives prepared via Morita-Baylis-Hillman reaction between a,p-unsaturated sugar aldehydes and activated olefins [(a) Gupta, M. K.; Sagar, R.; Shaw, A.K.; Prabhakar, Y. S. Bioorg. Med. Ozew.2005, 13, 343. (b) Pathak, R.; Pant, C. S.; Shaw, A. K.; Bhaduri, A. P.; Gaikwad, A. N.; Sinha, S.; Srivastava, A.; Srivastava, K. K.; Chaturvedi, V.; Srivastava, R.; Srivastava, B. S. Bioorg. Med Chem. 2002, 10, 3187. (c) Pathak, R.; Shaw, A. K.; Bhaduri, A. P.; Chandrasekhar, K. V. G.; Srivastava, A.; Srivastava, K. K.; Chaturvedi, V.;Srivastava, R.; Srivastava, B. S.; Arora, S.; Sinha, S. Bioorg. Med. Chem. 2002,10,1695].
Secondly cyclic deoxy sugars are known to be biologically important compounds, being structural components of several antibiotics and other important naturally occurring molecules [Georgiadis, M.P. J. Med .Chem. 1976, 19, 346]. These sugar derivatives can be derived by replacing one hydroxyl group from common sugars with a hydrogen or non-0-linked functional group [Laliberte, R.; Medawar, G.; Lefebvre, Y. J. Med .Chem. 1973, 16, 1084]. Such a substitution brings a fundamental change in the chemical
properties of the resulting sugar enhancing its thermodynamic stability and hydrophobicity.
Thirdly our belief was further strengthened by the report of Elias. A. Couladouros et al that derivatives of 2//-pyran-3(6#)-one (I) having structure very similar to unsaturated C-3-alkyl and -arylalkyl 2,3-dideoxy glucopyranosides exhibit significant antibacterial, antifungal, anticoccidial, anti-inflammatory, and anticancer properties besides serving as intermediates in several natural product syntheses [Laliberte, R.; Medawar, G.; Lefebvre, Y..7. Med.Chem. 1973,16, 1084]. (FigureRemoved)
Encouraged by the above literature report on antimicrobial properties of 2/f-pyran-3(6//)-one derivatives (I) and related compounds [(a)Georgiadis, M.P.; Couladouros, E.A.; Delitheos, A. K. J. Pharm. Sci 1992, 1126 , (b) Couladouros, E.A.; Strongilos, A.T. Angew. Chem., Int. Ed. Engl, 2002, 41, 3677] and the intriguing biological properdes of deoxysugars, we were prompted to develop the synthesis of C-3 branched enones derivatives of type I as antimycobacterial agents. Various synthetic methods have been reported for I and their derivatives [For the preparation of 2//-pyran-3(6//)-one derivatives (I) see references 1-9 in Georgiadis, M.P.; Couladouros, E.A.; Delitheos, A. K. J. Pharm. Sci. 1992, 1126]. However, based on the retro-synthetic scheme we identified deoxy enulosides 5a-c as a versatile synthetic intermediates to synthesize various molecules of the type I involving Morita-Baylis-Hillman chemistry [Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003,103, 811 & references cited therein].
In this endeavor we recently developed Morita-Baylis-Hillman chemistry of unsaturated C-3 branched deoxysugars [Sagar, R.; Pant, C. S.; Pathak, R.; Shaw, A. K. Tetrahedron
2004, 60, 11399] and now we wish to report herein the in vitro antimycobacterial activity of these deoxysugar derivatives.
The unpublished compounds of the series 6a are different from the published compounds of the series in terms of the R group used while in the case of 6b series the unpublished compounds differ from the published compounds both in terms of the R group used and their stereochemistry at C-4. While all the published compounds of series 6b have threo configuration the unpublished compounds of series 6b have erythro configuration.
The main objective of the present invention is to provide novel multifunctionalized unsaturated C-3-alkyl and - arylalkyl substituted 2,3-dideoxy glucopyranosides as anti-tubercular compounds.
Another objective of the present invention is to provide novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides as promising anti-tubercular compounds which are better and have more potential for further exploitation, than most of the previously known anti-tubercular molecules, as they are derived from monosaccharides which are known for their easy availability as sources of metabolic energy, high tolerance [Fischer, J. F.; Harrison, A.W.; Bundy, G.L.; Wilkinson, K.F.; Rush, B.D.; Ruwart, M. J. J. Med. Chem. 1991, 34 , 4140], improved pharmacokinetics [Negre, E.; Chance, M. L.; Hanbuta, S. Y.; Monsigny, M.; Roche, A. C.; Mayer, R. M. Antimicrob. Agents Chemother. 1992, 35, 2228], better transport [Wolform, M. L.; Hanessian, S. J. Org. Chem. 1962, 27, 1800], low toxicity and their role in recognition phenomena many of which are of great pharmacological relevance [Cipolla, L.; Ferla, B. L.; Nicotra, F. Carbohydr. Polym. 1998, 37, 291], and therefore have greater compatibility to the human body (living system) and thus are very suitable candidates for the development of new drugs.
Further these compounds being multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides derivatives are better from previously known anti-tubercular compounds because these novel molecules reported herein are deoxysugars, a distinct class of carbohydrates, which are thermally stable, hydrophobic in nature and play an important role in lipopolysaccharides, glycoproteins, and glycolipids, where they serve as ligands for cell-cell interactions or as targets for toxins, antibiotics

and microorganisms and because of these properties they have received special attention during the last few decades. [Hallis, T. M; Liu, H-W. Ace. Chem. Res. 1999, 32, 579]. Lastly, as it is being taken into account nowadays that small molecules are more stable, more active and whose synthesis can be easily developed [Wong, C-H. Ace. Chem. Res. 1999, 32, 376] therefore, these novel class of antitubercular compounds being monosaccharide derivatives (small molecules) are better from previously known carbohydrate derived anti-tubercular molecules most of which are macromolecules like oligosaccharides (antibiotics) or part of other large molecules. The significance of these novel molecules reported in this invention as lead molecules for the development of a new anti-TB drug can very well be gauged from the above arguments. Another major objective of the present invention is to provide novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6a and 6b which show promising in vitro activity against M. tuberculosis /fj7/?v. Accordingly, the present invention provides novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides 6aa, 6ab, 6ac, 6ad, 6ae, 6af, 6ag, 6ah, 6ai, 6aj, 6ak, 6ba, 6bb, 6bc, 6bd, 6be, 6bf, 6bg, 6bh which show in-vitro activity against M. tuberculosis H3?RV in a MIC range of 50 jxg/ml to 1.56 (o,g/ml. The objective of the present invention is also to provide a process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6a and 6b, a new series of novel compounds useful as anti-tubercular agents.
Accordingly, the present invention provides novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6a wherein R represents aryl groups selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group, while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by /?-nitrobenzoyl and different alkyl chlorides like tert-butyldimethylsilyl and tert-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl,
In another embodiment of the present invention wherein the present invention provides a process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6a which involves the following steps :
i) In another embodiment of the present invention wherein the reaction of 3,4,6-tri-O-acetyl-D-glucal of formula 1 with alcohols selected from the group consisting of methanol, propanol, isopropanol, butanol, isobutanol, sec-butanol, tert-butanol, pentanol, hexanol, heptanol, octanol, nonanol, decanol, sugar alcohols, all thioalcohols having upto ten carbons including substituted ones and thiol and variously substituted thiols in the presence of catalytic amount of la in an aprotic solvent viz tetrahydrofuron (THF) or by using lewis acids such as HfCU, ZrCU, BiCU, Cdla, Znk in solvents such as THF, dioxane, acetonitrile to furnish 2,3-dideoxy hex-2-enpyranoside derivative of formula 2. ii) In another embodiment of the present invention wherein the deacylation of formula 2 may be affected in methanol or ethanol with 2M sodium methoxide to obtain allylic alcohol of formula 3. This allylic alcohol can be isolated and purified by standard laboratory method such as column chromatography or crystallization, iii) In another embodiment of the present invention wherein the allylic oxidation of 3 is effected with oxidizing agents such as manganese dioxide (MnO2) in chloroform or dichloromethane solvent at room temperature or using Dess-Martin periodinane oxidation method to furnish 2,3-dideoxy hexenopyranoside-4-uloses of formula 4. These 2,3-
dideoxy hexenopyranoside-4-uloses can be isolated and purified by standard laboratory method such as column chromatography.
iv) In another embodiment of the present invention wherein the C-6 protection of 4 may be effected by using acetic anhydride with dry pyridine as solvent and dimetylaminopyridine (DMAP) as catalyst or by using acyl chlorides such as trimethylacetyl chloride, 4-nitrobenzoyl chloride in dry pyridine as solvent and dimetylaminopyridine (DMAP) as catalyst or using alkyl chlorides such as tert-butyl dimethyl silyl and tert-butyl diphenylsilyl chloride using dry dichloromethane as solvent or to furnish the compounds of formula 5 wherein R' represents the acetyl group, trimethyl acetyl group, p-nitrobenzoyl, ter/-butyl dimethyl silyl, tert-butyl diphenylsilyl respectively These protected 2,3-dideoxy hexenopyranoside-4-uloses of formula 5 can be purified by column chromatography.
v) In another embodiment of the present invention wherein the formation of Baylis-Hillman adduct of general formula 6a may be effected by reacting various aliphatic and aromatic aldehydes with 5 to furnish the Morita-Baylis-Hillman adducts of formula 6a. The aliphatic aldehyde used may be selected from the group consisting of all aliphatic aldehydes having up to ten carbons and their amino, hydroxyl and keto substituted derivativatives, trihalomethylaldehyde such as chloral whereas aromatic aldehydes used may be selected from a the group consisting of all mono, di, tri, variously substituted benzaldehydes, all mono, di, tri, variously substituted aromatic heterocyclic aldehydes in the presence of lewis acids selected from the group consisting of TiCU, ZrCU, HfCLj, in different quantities and bases from the group consisting of TBAI, EtsN, PhsP, (Me)2S or lewis acids selected from the group consisting of ZnI2, Cdb, Cuh in different quantities in dry solvents from the group consisting of dichloromethane, chloroform, dioxane, tetrahydrofuran and acetonitrile in a temperature range of-78°C to 150°C.
In another embodiment of the present invention wherein the present invention provides novel multi-functionalized unsaturated C-3-alkyl and -arylalkyl substituted erythro 2,3-dideoxy glucopyranosides of general formula 6b wherein R represents aryl groups selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups
consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group, while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by ;?-nitrobenzoyl and different alkyl chlorides like tert-butyldimethylsilyl and tert-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars and OR" as a whole represents thiol and all substituted thiols.
In another embodiment of the present invention wherein the present invention provides a process for stereoselective reduction of C-4 keto group of unsaturated C-3 -alkyl and -arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6a by stirring them in solvents selected from the group consisting of methanol and ethanol using reducing agents selected from the group consisting of sodium borohydride, sodium triacetoxyborohydride and sodium cyanoborohydride in different quantities in the presence of CeCh.TFkO in different quantities for 1-3 h to furnish the erythro derivative of C-3-alkyl and -arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6b in good yield. These erythro derivatives of general formula 6b can be isolated and purified by standard laboratory method such as column chromatography. Accordingly the present invention also provides a pharmaceutical composition comprising therapeutically effective amount of compound of general formula 6 optionally along with pharmaceutically acceptable carriers, diluents and exciepients.
In an embodiment of the invention wherein the composition is useful for the treatment of tuberculosis.
The compounds 1-5 are known in the literarature and are prepared by known methods
a). Pre'vost, N.; Rouessac, F. Synth. Commun. 1997,27, 2325-2335.
b). Sagar, R.; Pant, C. S.; Pathak, R.; Shaw, A. K. Tetrahedron 2004, 60, 11399-11406
Water soluble derivatives of compounds of series 6a and 6b may be prepared by incorporation of the polar amino group and their salts in the form of hydrochloride or sulphate, or other polar groups such as amide and acid groups etc, into the molecules of the aforesaid series.
The invention is further illustrated by the following examples which should not however be construed to limit the scope of the present invention.
EXAMPLE I
Isopropyl-6-0-trimethyIacetyI-3-[hydroxy (4-cyanophenyl) methyI]-2,3-dideoxy-a-D-g/Vc^ro-hex-2-enopyranoside-4-ulose (Compound 6aa)
To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CF^C^ (5 mL) at -78°C was added TiCU (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, trimethylacetyl (pivaloyl) protected enuloside 5a (1.0 mmol) and 4-cyanobenzaldehyde (2.0 mmol) in dry CP^Ch (5 mL) was added to the reaction mixture. The reaction mixture was slowly warmed to -30°C and stirred for 48 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6aa as oil [94%].
Example II
Isopropyl-6-O-trimethylacetyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-^(vcero-hex-2-eno pyranoside-4-ulose (Compound 6ab)
To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2Cl2 (5 mL) at -78°C was added TiCU (1.5 mmol) dropwise. After stirring for two minutes, a
mixture containing, trimetylacetyl (pivaloyl) protected enuloside 5a (1.0 mmol) and decanal (2.0 mmol) in dry CH2C12 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for SOhrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ab as oil [81%].
Example III
Isopropyl-6-0-trimethylacetyl-3- [hydroxy (3-nitrophenyl) methyl] -2,3-dideoxy-a-D-g(ycer0-hex-2-enopyranoside-4-ulose (Compound 6ac)
To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCL* (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, trimetylacetyl (pivaloyl) protected enuloside 5a (1.0 mmol) and 3-nitrobenzaldehyde (2.0 mmol) in dry CH2C12 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 10 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ac as oil [64%].
Example IV
Isopropyl-6-0-trimethylacetyI-3-[hydroxy (4-trifluoromethylphenyl) methyl]-2,3-dideoxy-a-D-£(ycm>-hex-2-enopyranoside-4-ulose (Compound 6ad) To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, trimetylacetyl (pivaloyl) protected enuloside 5a (1.0 mmol) and 4-trifluromethylbenzaldehyde (2.0 mmol) in dry CH2C12 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 10 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad.
The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ad as oil [86%].
Example V
Isopropyl-6-0-4-nitrobenzoyI-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-£/ycero-hex-2-enopyranoside-4-ulose (Compound 6ae)
To a stirred solution of tetrabutylammonium iodide, THAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and 4-nitrobenzaldehyde (2.0 mmol) in dry CH2Cl2 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 6 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ae as oil [88%].
Example VI
Isopropyl-6-0-4-nitrobenzoyl-3-[hydroxy (4-trifluromethyl phenyl) methyl]-2,3-dideoxy-a-D-£(ycer0-hex-2-enopyranoside-4-ulose (Compound 6af)
To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2Cl2 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and 4-trifluromethylbenzaldehyde (2.0 mmol) in dry CHbCh (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 11 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution,
dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6af as oil [86%].
Example VII
Isopropyl-6-0-4-nitrobenzoyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-#/jcer0-hex-2-enopyranoside-4-ulose (Compound 6ag)
To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCLj (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and decanal (2.0 mmol) in dry CHaC^ (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 33 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ag as oil [87%].
Example VIII
Isopropyl-6-0-4-nitrobenzoyl-3- [hydroxy (4-cyanophenyl) methyl] -2,3-dideoxy-a-D-£/ycer0-hex-2-enopyranoside-4-ulose (Compound 6ah)
To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry Cf^Ck (5 mL) at -78°C was added TiCU (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and 4-cyanobenzaldehyde (2.0 mmol) in dry CHaCb (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 7 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ah as oil [86%].

Example IX
Isopropyl-6-0-4-nitrobenzoyl-3-[hydroxy (4-fluorophenyl) methyl]-2,3-dideoxy-a-D-£(ycer0-hex-2-enopyranoside-4-ulose (Compound 6ai)
To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and 4-flurobenzaldehyde (2.0 mmol) in dry CH2Cl2 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 21 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ai as oil [70%].
Example X
Isopropyl-6-0-4-nitrobenzoylO-(l-hydroxybutyl)-23-dideoxy-a-D-£/ycm>-hex-2-enopyranoside-4-ulose (Compound 6aj)
To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCU (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, 4-nitrobenzoyl protected enuloside 5b (1.0 mmol) and butanal (2.0 mmol) in dry CH2C12 (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for the 24 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6aj as oil [84%].
Example XI
Isopropyl-6-0-acetyl-3-[hydroxy (4-nitrophenyl) methyl] -2,3-dideoxy-o>D-g(ycer0-hex -2-enopyranoside-4-ulose (Compound 6ak)
To a stirred solution of tetrabutylammonium iodide, TBAI, (0.2 mmol) in dry CH2C12 (5 mL) at -78°C was added TiCl4 (1.5 mmol) dropwise. After stirring for two minutes, a mixture containing, acetyl protected enuloside 5c (1.0 mmol) and 4-nitrobenzaldehyde (2.0 mmol) in dry CHaCb (5 mL) was added. The reaction mixture was slowly warmed to -30°C and stirred for 5 hrs. A saturated aqueous solution of sodium bicarbonate was added, followed by filtration through a celite pad. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate (4x5ml). The combined organic layer was washed with brine solution, dried over sodium sulfate and evaporated in vacuo to get the crude product. The crude product was chromatographed to yield the pure compound 6ak as oil [64%].
Example XII
Isopropyl-6-6Mrimethylacetyl-3-[hydroxy (4-cyanophenyl) methyl]-2,3-dideoxy-a-D-erythro-he\-2-enopyranoside (Compound 6ba)
To a stirred solution of the compound 6aa in ethanol (10ml), NaBtLt (0.5 mmol) and CeCls.TtbO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 5h. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6ba in 75% yield.
Example XIII
Isopropyl-6-O-trimethylacetyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-erv//iro-hex-2-enopyranoside (Compound 6bb).
To a stirred solution of the compound 6ab in ethanol (10ml), NaBRt (0.5 mmol) and CeCla.THaO (1.0 mmol) were added and the reaction mixture'was stirred continuously at room temperature for the 5hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bb in 68% yield.
Example XIV
Isopropyl-6-0-trimethylacetyl-3-[hydroxy (3-nitrophenyl) methyI]-2,3-dideoxy-o-D-erythro-hex-2-enopyranoside (Compound 6bc).
To a stirred solution of the compound 6ac in ethanol (10ml), NaBH4 (0.5 mmol) and CeCls.THaO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 3hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bc in 90% yield.
Example XV
Isopropyl-6-6Mrimethylacetyl-3-[hydroxy (4-trifluoromethylphenyl) methyl]-2,3-dideoxy-a-D-£ryfAro-hex-2-enopyranoside (Compound 6bd).
To a stirred solution of the compound 6ad in ethanol (10ml), NaBH4 (0.5 mmol) and CeCla.TFhO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 4hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bd in 80 % yield.
Example XVI
Isopropyl-6-0-4-nitrobenzoyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-eryfAro-hex-2-enopyranoside (Compound 6be).
To a stirred solution of the compound 6ae in ethanol (10ml), NaBRj (0.5 mmol) and CeCls.ytbO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 6hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6be in 75% yield.
Example XVII
IsopropyI-6-0-4-nitrobenzoyl-3-[hydroxy (4-trifluromethyl phenyl) methyl]-2,3-dideoxy-a-D-erv^ro-hex-2-enopyranoside (Compound 6bf).
To a stirred solution of the compound 6af in ethanol (10ml), NaBPL; (0.5 mmol) and (1.0 mmol) were added and the reaction mixture was stirred continuously at
room temperature for the 3hrs. After completion of the reaction (TLC control), excess NaBPLt was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bf in 80%yield.
Example XVIII
Isopropyl-6-6M-nitrobenzoyl-3-(l-hydroxydecyl)-23-dideoxy-a-D-eiyfAr0-hex-2-enopyranoside (Compound 6bg).
To a stirred solution of the compound 6ag in ethanol (10ml), NaBH4 (0.5 mmol) and CeCl3.7H2O (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 6 hrs. After completion of the reaction (TLC control), excess NaBH4 was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bg in 87% yield.
Example XIX
Isopropyl-6-0-acetyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideo\y-a-D-erythro-hex -2-enopyranoside (Compound 6bh).
To a stirred solution of the compound 6ak in ethanol (10ml), NaBtLt (0.5 mmol) and CeCb.THaO (1.0 mmol) were added and the reaction mixture was stirred continuously at room temperature for the 2h. After completion of the reaction (TLC control), excess NaBHU was neutralized with acetone and the reaction mixture was concentrated in vacuo to get crude product which on column chromatography yielded the pure compound 6bh in 73 % yield.
ADVANTAGES
i) All the compounds of series 6a and 6b reported in this invention are novel. They have
been reported for the first time.
ii) The compounds of series 6a and 6b reported in this invention have been reported to
show anti-TB activity for the first time. The compounds 6aa, 6ab, 6ac, 6ad, 6ae, 6af,
6ag, 6ah, 6ai, 6aj, 6ak, 6ba, 6bb, 6bc, 6bd, 6be, 6bf, 6bg, 6bh have been reported to
show in-vitro activity against M. tuberculosis //37^?v in a MIC range of 50 ng/ml to 1.56
ug/ml.
iii) The most active compounds of series 6a and 6b reported in this invention showed little or no cytotoxicity on being tested on VERO cell line.
iv) The novel compounds of series 6a and 6b are promising anti-tubercular compounds which are better and have more potential for further exploitation, than most of the previously known anti-tubercular molecules, as they are derived from monosaccharides which are known for their easy availability as sources of metabolic energy, high tolerance improved pharmacokinetics, better transport, low toxicity and their role in recognition phenomena many of which are of great pharmacological relevance, and therefore have greater compatibility to the human body (living system) and thus are very suitable candidates for the development of new drugs.
Further these compounds being multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides derivatives are better from previously known anti-tubercular compounds because these are deoxysugars. Deoxysugars a distinct class of carbohydrates, which are thermally stable, hydrophobic in nature and play an important role in lipopolysaccharides, glycoproteins, and glycolipids, where they serve as ligands for cell-cell interactions or as targets for toxins, antibiotics and microorganisms and because of these properties they have received special attention during the last few decades. Lastly, as it is being taken into account nowadays that small molecules are more stable, more active and their synthesis can be easily developed therefore, these novel class of antitubercular compounds being monosaccharide derivatives (small molecules) are better from previously known carbohydrate derived anti-tubercular molecules most of which are macromolecules like oligosaccharides (antibiotics) or part of other large molecules. The significance of these novel molecules reported in this invention as lead molecules for the development of a new anti-TB drug can very well be gauged from the above arguments.
v) All the compounds of series 6a and 6b reported in this invention have been prepared by reacting protected 2,3-dideoxy hexenopyranoside-4-uloses of formula 5 with different aldehydes using Morita-Baylis-Hillman chemistry. Morita-Baylis Hillman (MBH) chemistry has been recognized as one of the most versatile and more economically feasible C-C bond forming reactions to generate multifunctionalized allylic alcohols generally called MBH or BH adducts. Use of this methodology thus provides a most
versatile and economically viable route for the preparation of a large number of BH
adducts of 6a series using different aldehydes and their reduced forms (6b series).
vi) The compounds of series 6a and 6b were prepared using easily available, inexpensive
and benign reagents like TiCU and TBAI in dichloromethane.
vii) Taking into consideration points (i) to (vi) leads to the conclusion that the novel
series of compounds 6a and 6b provide a new, most promising lead for the development
of a potent new anti -TB drug. This importance of this invention lies in the fact that it
provides a new, entirely different lead for the development of a potent new anti -TB drug
based upon monosaccharide derived 2-deoxy sugar opening up a new, promising, hitherto
unexplored chapter in the race for the development of a badly needed potent new anti-TB
drug.
ANTITUBERCULAR ACTIVITY Agar dilution method
Briefly, 2-fold serial dilutions of each test compound/drug were incorporated into 7H10 agar. Inoculum of M. tuberculosis H37Rv was prepared from fresh Lowenstein-Jensen slants adjusted to 1 mg/mL (wet weight) in Tween 80 (0.05%) saline and diluted to 10"2 to give a concentration of approximately 107 cfu/mL. 5 mL of bacterial suspension was spotted into 7H10 agar tubes containing 2-fold serial dilution of drugs per mL. The tubes were incubated at 37°C and final readings were recorded after 30 days. The MICs were read as the minimum concentration of drugs/compounds that completely inhibited the growth of M tuberculosis per spot. Ofloxacin was used as the standard drug. Microwell plate alamar blue assay (MABA)
Antimycobacterial activity was determined by Microwell plate based Alamar blue assay (MABA) using M. tuberculosis H37Ra as a surrogate for the virulent H37Rv strain. The results of MABA have been found comparable to the standard agar dilution system based assay. The standard antitubercular drugs Rifamycin, Isoniazid, p-Amino salicylic acid, Ethambutol and Ethionamide (MIC range 3 Drug susceptibility testing by BACTEC radiometric susceptibility assay:
The assay was done using M. tuberculosis H37Rv as test stain. The assay grows M tuberculosis in 7H12 medium containing 14C labeled palmitic acid as substrate and 14CC>2 is produced. The amount of I4CC>2 detected reflects the rate and amount of growth occurring in the vial and is expressed in term of the "Growth Index" (GI). On addition of an antitubercular drug to the medium suppression of growth of the test organism M tuberculosis can be detected by either a decline or very small increase of the daily GI output as compared to the control. Streptomycin (6ug/ml) and Rifampin (2ug/ml) were used as positive control. All compounds showing MIC below 25(j,g/ml in agar tube dilution were confirmed for activity against M. tuberculosis HjyRv by BACTEC radiometric assay. Cytotoxicity studies
The most active compounds 6aa, 6ab, 6bb and 6ak were tested for their cytotoxicity in VERO cell line. VERO cells originally obtained from ATCC and maintained in CDRI, were seeded on a 96 well plate and incubated at 37°C in 5% CC^ and 95% air. Cells were exposed to varying concentrations (25, 50, 100 ug/ml) of the compound for 72 hours. MTT assay was performed as per the standard protocol to assess cell viability. Triplicates of each assay were carried out. 6ab, 6bb and 6ak were found to be cytotoxic at 25 ug/ml while 6aa showed no cytotoxicity at the dose of 100 ug/ml. Cytotoxicity was also observed for mouse macrophage cell line J 744A.I which is an important cell line for M tuberculosis infection has been used for the assay. The assay is based on the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] reduction. The drug concentrations used for the assay were 50, 25 and 12.5 ug/ml, in parallel with known toxic compounds and standard antimycobacterial drugs like Rifampicin and Sparfloxacin. The cell death was significantly lower (8-10-fold) than the toxic compound and very similar to standard drugs.
Tablel. Antimycobacterial activity against M. tuberculosis H^RV by agar dilution
(TableRemoved)

WE CLAIM
1) A novel multifunctionalized unsaturated C-3-alkyl or arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6 Wherein R represents aryl group selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group, while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by p-nitrobenzoyl and different alkyl chlorides like tert-butyldimethylsilyl and terf-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars and OR" as a whole represents thiol and all substituted thiols , pharmaceutically acceptable salts and derivatives therof.
(Formula removed)
2) A compound as claimed in claim (1) of the structure of general formula 6 wherein the structure of the 4-keto compound is as follows
formula removed
i) wherein R represents aryl groups selected from the groups consisting of mono, di, tri,
substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and
alkyl groups selected from the groups consisting of all alkyl groups containing upto ten
carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group,
ii) R' represents hydrogen, alkyl acyl groups selected from the groups consisting of acetyl
and pivaloyl and aryl acyl group represented by p-nitrobenzoyl and different alkyl
chlorides like terr-butyl dimethyl silyl and tert-butyl diphenylsilyl chloride,
iii) R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl,
isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl,
and sugars,
iv) OR" as a whole represents thiol and all substituted thiols,
3) A compound as claimed in claim 1 wherein the structure of the 4-erythro derivative of
general formula 6a compound is as follows:

i) wherein R represents aryl groups selected from the groups consisting of mono, di, tri,
substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and
alkyl groups selected from the groups consisting of all alkyl groups containing upto ten
carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group.
ii) R' represents hydrogen, alkyl acyl groups selected from the groups consisting of acetyl
and pivaloyl and aryl acyl group represented by p-nitrobenzoyl and different alkyl
chlorides like ter/-butyl dimethyl silyl and tert-butyl diphenylsilyl chloride,
iii) R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl,
isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl,
and sugars,
iv) OR" as a whole represents thiol and all substituted thiols.
4) The compound as claimed in claim 1 wherein the representative compounds of general formula 6a and 6b are given below:
i) Isopropyl-6-0-trimethylacetyl-3-[hydroxy (4-cyanophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6aa)
ii) Isopropyl-6-O-trimethylacetyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ab)
iii) Isopropyl-6-0-trimethylacetyl-3-[hydroxy (3-nitrophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ac)
iv) Isopropyl-6-0-trimethylacetyl-3-[hydroxy (4-trifluoromethylphenyl) methyl]-2,3-dide oxy- v) Isopropyl-6-0-4-nitrobenzoyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose(6ae)
vi) Isopropyl-6-O-4-nitrobenzoyl-3-[hydroxy (4-trifluromethyl phenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6af)
vii) Isopropyl-6-O-4-nitrobenzoyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ag)
viii) Isopropyl-6-O-4-nitrobenzoyl-3-[hydroxy (4-cyanophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ah)
ix) Isopropyl-6-O-4-nitrobenzoyl-3-[hydroxy (4-fluorophenyl) methyl]-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6ai)
x) Isopropyl-6-O-4-nitrobenzoyl-3-(l-hydroxybutyl)-2,3-dideoxy-a-D-g/ycero-hex-2-enopyranoside-4-ulose (6aj)
xi) Isopropyl-6-Oacetyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-g/vcero-hex-2-enopyranoside-4-ulose (6ak)
xii) Isopropyl-6-0-trimethylacetyl-3-[hydroxy (4-cyanophenyl) methyl]-2,3-dideoxy-a-D-
erythro-hex-2-enopyranoside (6ba).
xiii) Isopropyl-6-O-trimethyl acetyl-3-(l-hydroxy decyl)-2,3-dideoxy-a-D-erytfzro-hex-
2-enopyranoside (6bb).
xiv) Isopropyl-6-(9-trimethylacetyl-3-[hydroxy (3-nitrophenyl) methyl]-2,3-dideoxy-a-D-
ery^ro-hex-2-enopyranoside (6bc).
xv) Isopropyl-6-O-trimethylacetyl-3-[hydroxy (4-trifluoromethylphenyl) methyl]-2,3-
dideoxy-a-D-er>tf/zr0-hex-2-enopyranoside(6bd).
xvi) Isopropyl-6-O4-nitrobenzoyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-
ery//zro-hex-2-enopyranoside(6be).
xvii) Isopropyl-6-O4-nitrobenzoyl-3-[hydroxy (4-trifluromethyl phenyl) methyl]-2,3-
dideoxy-a-D-ery//zro-hex-2-enopyranoside6bf).
xviii) Isopropyl-6-O-4-nitrobenzoyl-3-(l-hydroxydecyl)-2,3-dideoxy-a-D-ery^/zro-hex-2-
enopyranoside (6bg).
xix) Isopropyl-6-0-acetyl-3-[hydroxy (4-nitrophenyl) methyl]-2,3-dideoxy-a-D-erythro-
hex-2-enopyranoside (6bh).
5) A novel compound as claimed in claim 1 wherein the novel compounds of series 6a
and 6b showed anti-tubercular activity for the first time.
6) A novel compound as claimed in claim 1 wherein the novel compounds of series 6a
and 6b showed activity for the first time against the strain of mycobacterium tuberculi
H37Ra.
7) A novel compound as claimed in claim 1 wherein the novel compounds of series 6a
and 6b showed activity for the first time against the strain mycobacterium tuberculi
8) A process for the preparation of novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6 as claimed in claim 1 comprising the following steps :
i) providing the compound of formula 5 by known methods followed by formation of Baylis-Hillman adduct of general formula 6 by reacting compound of formula 5 with aliphatic or aromatic aldehydes in the presence of a lewis acid and a base in a
chlorinated aprotic solvent or non-chlorinated aprotic solvent at a temperature ranging between -78 °C to 150 °C to furnish the Morita-Baylis-Hillman adducts of formula 6a, ii) stereoselective reduction of C-4 keto group of unsaturated C-3-alkyl and -arylalkyl substituted 2,3- dideoxy glucopyranosides of general formula 6a obtained in step (v) by stirring in polar protic solvent using reducing agent optionally in presence of CeCls for 1-7 hr to furnish the erythro derivative of C-3-alkyl or arylalkyl substituted 2,3-dideoxy glucopyranosides of general formula 6b, isolating and purifying by standard laboratory method such as column chromatography.
9) A process as claimed in claim (8) wherein the base used in step (i) is selected from the group consisting of pyridine, triethylamine.
(10) A process as claimed in claim (8) wherein the solvent used in step (i) is selected
from aprotic chlorinated solvents from the group consisting of chloroform
dichloromethane, 1,2-dichloroethane.
(11) A process as claimed in claim (8) wherein the aldehyde used in step (i) is selected
from the group consisting of aliphatic aldehydes such as all aliphatic aldehydes having
upto ten carbons and their amino, hydroxyl and keto substituted derivatives,
trihalomethylaldehyde such as chloral etc. or from a group consisting of aromatic
aldehydes such as all mono, di, tri, variously substituted benzaldehydes, all mono, di, tri,
variously substituted aromatic heterocyclic aldehydes.
(12) A process as claimed in claim (8) wherein the lewis acid used in step (i) is selected
from the group consisting of TiCU, ZrCU, HfCU, Zn, Cdla, Cul2.
(13) A process as claimed in claim (8) wherein the base used in step (i) is selected from
the group consisting of TBAI, triethylamine, triphenylphosphine, dimethyl sulfide .
(14) A process as claimed in claim (8) wherein the solvent used in step (i) is selected
from chlorinated aprotic solvents from the group consisting of, dichloromethane, 1,2-
dichloroethane , chloroform, etc. or non-chlorinated aprotic solvents selected from the
group consisting of THF, acetonitrile, dioxane, diethylether.
15) A process as claimed in claim (8) wherein the reducing agent used is selected from the group consisting of sodium borohydride, sodium cyanoborohydride, sodium triacetoxy borohydride.
(16) A process as claimed in claim (8) wherein the solvent used in step (ii) is selected
from polar protic solvents from the group consisting of methanol, ethanol, 1,2-etanediol
etc.
17. A process as claimed in claim (8) wherein the Water soluble derivatives of
compounds of series 6a and fib may be prepared by incorporation of the polar amino
group and their salts in the form of hydrochloride or sulphate, or other polar groups such
as.amide and acid groups etc. into the molecules .
17) Use of novel compounds of general formula 6a and 6b as claimed in claim (1) for the
treatment of Tuberculosis.
18) Use of novel multifunctionalized unsaturated C-3-alkyl and -arylalkyl substituted 2,3-
dideoxy glucopyranosides of general formula 6a and their reduced derivatives having
general formula fib as claimed in claim (7) wherein the MIC value of the representative
compounds fiaa, 6ab, fiac, fiad, 6ae, fiaf, fiag, fiah, fiai, fiaj, fiak, fiba, fibb, 6bc, fibd,
fibe, fibf, fibg, fibh are in a range of 50 ug/ml to 1.56 ug/ml.
24) Use as claimed in claim 22 wherein in vitro activity against M. tuberculosis Hi7Rv shown by the representative compounds fiaa, fiab, fiac, fiad, fiae, fiaf, fiag, fiah, fiai, fiaj, fiak, fiba, fibb, fibc, fibd, fibe, fibf, fibg, fibh are in a MIC range of 50 ng/ml to 1.56 ug/ml.
19) Use as claimed in claim 17 wherein in vitro and in vivo activity against M.
tuberculosis //37/?v shown by any of the novel compounds claimed in claim (1), (2), (3)
and"(4).
20) Use as claimed in claim 17 wherein the most active compounds of the novel series of
compounds of general formula 6a and fib reported in this invention showed little or no.
cytotoxicity on being tested on VERO cell line.
21) A Pharmaceutical composition comprising therapeutically effective amount of
compound of general formula 6
22) Wherein R represents aryl group selected from the groups consisting of mono, di, tri, substituted phenyl groups, mono, di, tri, substituted aromatic heterocyclic groups and alkyl groups selected from the groups consisting of all alkyl groups containing upto ten carbons and all their amino and hydroxyl substituted derivatives and trihalomethyl group, while R' represents, hydrogen, alkyl acyl groups selected from the groups consisting of acetyl and pivaloyl and aryl acyl group represented by j9-nitrobenzoyl and different alkyl chlorides like tert-butyldimethylsilyl and tert-butyldiphenylsilyl chloride and while R" represents alkyl groups selected from groups consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, and sugars and OR" as a whole represents thiol and all substituted thiols optionally along with pharmaceutically acceptable carriers, diluents and exciepients. 22) A Novel multifunctionalized unsaturated C-3-alkyl or -arylalkyl substituted 2,3-dideoxy glucopyranosides substantially as herein described with reference to the examples and drawings accompanying the specification.

Documents:

533-del-2006-abstract.pdf

533-del-2006-claims.pdf

533-del-2006-correspondence-others-1.pdf

533-del-2006-correspondence-others.pdf

533-del-2006-description (complete).pdf

533-del-2006-drawings.pdf

533-del-2006-form-1.pdf

533-del-2006-form-18.pdf

533-del-2006-form-2.pdf

533-del-2006-form-3.pdf

533-del-2006-form-5.pdf

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Patent Number

257469

Indian Patent Application Number

533/DEL/2006

PG Journal Number

41/2013

Publication Date

11-Oct-2013

Grant Date

05-Oct-2013

Date of Filing

28-Feb-2006

Name of Patentee

COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

Applicant Address

ANUSANDHAN BHAWAN, RAFI MARG, NEW DELHI - 110 001, INDIA.

Inventors:

#	Inventor's Name	Inventor's Address
1	RAM SAGAR	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.
2	MOHD. SAQUIB	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.
3	ARUN KUMAR SHAW	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.
4	ANIL NILKANTH GAIKWAD	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.
5	SUDHIR KUMAR SINHA	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.
6	ANIL SRIVASTAVA	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.
7	VINITA CHATURVEDI	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.
8	RANJANA SRIVASTAVA	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.
9	MANJU YASHODA KRISHNAN	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.
10	BRAHM SHANKER SRIVASTAVA	CENTRAL DRUG RESEARCH INSTITUTE, CHATTAR MAZIL PALACE, POST BOX NO 173, LUCKNOW 226 001, INDIA.

PCT International Classification Number

C07H 15/04

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA