Title of Invention

NOVEL 3-SULFANYL CYCLIC KETONES

Abstract

This method provides preparation of 13-thiaprostaglandin derivatives racemic or optically active depending upon the cyclic enone using zeolite catalyst which can be removed by filtration reused and recycled. This process provides cheaper methodology of preparing biologically important compounds. Thioprostaglandin are chemically and biologically stable analogs of naturally occurring prostaglandins therefore may be advantageous provided their biological activity is comparable which is yet to be explored.

Full Text

This invention relates to novel 3-sulfanyl cyclic ketones This invention particularly relates to novel 3-sulfanyl cyclic ketones of formula 3 wherein, A is methylene or ethylene, R may be hydrogen or methyl-7-heptanoate, R1 may be hydrogen, hydroxy, ter-butyldimethylsilyloxy, triethylsilyloxy, or trimethylsilyloxy:, and R2 may be, 2-hydroxyethylsulfanyl, 2-hydroxy-3-(4-methoxylphenyloxy)propylsulfanyl, 2-hydroxy-3-( 1-naphthyloxy)propyisulfanyl or 2-hydroxy-3-(2-naphthyloxy)propylsulfanyl. This invention also relates to a process for the preparation of 3-sulfanyl cyclic ketones More particularly it relates to the zeolite catalysed 1,4-addition (Michael addition) of thiols having formula (1) to cyclic enones having general formula (2) in the drawing accompanying this specification wherein, A is methylene or ethylene, R may be hydrogen or methyl-7-heptanoate, RI may be hydrogen, hydroxy, ter-butyldimethylsilyloxy, triethylsilyloxy, or trimethylsilyloxy; into cyclic ketones of the general formula (3) in the drawing accompanying this specification wherein; A, R, and RI are as above (for 2) and R2 may be 4-chlorothiophenyl, 4-methylthiophenyl, 2-hydroxyethylsulfanyl, 2-hydroxy-3-(4-methoxylphenyloxy)propylsulfanyl, 2-hydroxy-3-(l-naphthyloxy)propyl-sulfanyl or 2-hydroxy-3-(2-naphthyloxy)propylsulfanyl. Still more particularly it relates to process for the preparation of 13-thiaprostaglandin derivatives. This method provides preparation of 13-thiaprostaglandin derivatives racemic or optically active depending upon the cyclic enone used. 13-Thiaprostaglandin derivatives are biologically active molecules, e.g. prosolvin is marketed as a veterinary luteolytic drug Some other analogues are useful in the treatment of glaucoma, ocular hypertension and high blood pressure. It is believed that the 13-sulfur atom acts as a bioisostere of the 13, 14-( cis ) double bond of the normal prostaglandin omega chain The compounds of formula (3) wherein; A is methylene, R is 7-heptanoic acid, R1 is hydroxy and R2 is 2-hydroxy-3-(4-chloro or methoxyphenyloxy)propylsulfanyl have been prepared by generally employing the methods disclosed in the forgoing references either alone or in combination with other methods. Base catalysed addition of thiols on the cyclic enone system of the formula 2 with the corresponding substituents in the drawing accompanying this specification is known in the literature wherein organic bases like diisopropylamine, piperidine, triethylamine etc are used Heterogenous or inorganic catalysts such as clays, Y-type zeolites, heteropolyacids, H-ZSM-5, LaN?trts-(binaphthoxide), SmNa3 tris (binaphthoxide) have been employed for Michael addition of different substrates wherein in some reports alcohols are used instead of thiols. Y-type zeolites have been used for Michael addition of thioacetic acid to acyclic α,ß-unsaturated carboxylic acid esters. The x- and y-type zeolites are alluminosilicates with different percentages of aluminum and silica. They are commercially available or can be prepared by known methods (D.W.Breck, "Zeolite Molecular Sieves Structure, chemistry and use", London, Wiley (1974). Some of the related references are: Radunz H.E., Orth D., Baumgarth M , Schliep H.J . and Enenkil H.J., U.S.P. 4,309,441 (1982); Hess H.J.E and Schaaf T.K , U.S.P.4,1 52,527 (1979); Emon E., Arai T., Sasai H; and Shibasaki M.; J Am. Chem. Soc 1998, 120, 4043, Kengaku T., Matsumoto Y., NaK, Misono M, J.Mol.Catal, A.Chem 1998; 134, 237, Sreekumar R, Rugmini P, Padmakumar R., Tet.Lett. 1997, 38, 6557, Nishi M., Fujihara H., Yoshihara M , Maeshima T., Nihon Yukagakkaishi 1997; 46, 899, Taniguchi Y, Maruo M., Takaki K And Fujiwara Y, Tet.Lett. 1994, 35, 7789, Sera A., Takaki K., Katayama H. and Yamada H. J Org Chem. 1988,53, 1157 The inventors of the present invention are reporting for the first time the application of x-type zeolites doped with lithium, potassium or cesium metal for 1,4-addition of thiols to a cyclic enone system of the formula 2 and the preparation of compounds of the formula 3 Some of the compounds of the formula 3 prepared and reported by the present process are novel. The hitherto known methods using organic bases resulted into side products and disulfide formation as major component during the preparation of the compounds of the formula 3. However, the disulfide formation has been minimized by employing the zeolite catalyst which maintains neutral conditions for the reaction. The object of the present invention is therefore to provide a process for the preparation of 3-sulfanyl cyclic ketones using x-type zeolite with lithium / potassium / cesium cations Accordingly, the present invention provides novel 3-sulfanyl cyclic ketones having the general formula 3 of the drawing accompanying the specification wherein; A is methylene or ethylene, R may be hydrogen or methyl -7-heptanoate, RI may be hydrogen, hydroxyl, ter-butyldimethylsilyloxy, triethysilyloxy, or trimethylsilyloxy; and R2 may be 2-hydroxyethylsulfanyl, 2-hydroxy-3-(4-chloro or methoxyphenyloxy)propylsulfanyl, 2-hydroxy-3-(1-naphthyloxy)propyl-sulfanyl or 2- hydroxy-3-(1-naphthyloy)propyl-sulfanyl or 2-hydroxy-3-(2-naphthyloxy) propylsulfanyl. A process for the preparation of 3-sulfanyf cyclic ketones of the general formula 3 wherein; A is methylene or ethylene, R may be hydrogen or methyl-7-heptanoate, R1 may be hydrogen, hydroxyl, ter-butyldimethylsilyloxy, triethysilyloxy, or trimethysilyloxy; and R2 may be 4-chloro thiophenyl 4-methylthiophenyl, 2-hydroxyethylsulfanyl, 2-hydroxy-3-(4-methoxy phenyloxy)propylsulfanyl, 2-hydroxy-3-(1-naphthyloxy)propyl-sulfanyl or 2-hydroxy-3-(2-naphthyloxy)propylsulfanyl, which comprises; preparing a solution of cyclic a, p-unsaturated ketone (enone) in an organic solvent, mixing thiols, adding x-type zeolite catalyst under stirring at 10 to -10°C, continuing agitation for a period of 1.5 to 2 hr, warming the reaction mixture to room temperature, stirring further for a period of 24 to 50 hr, separating the catalyst by conventional methods, washing with the same organic solvent, washing the organic filtrate with water and brine, drying the organic layer over a dehydrating agent, concentrating the dehydrated organic layer under reduced pressure to obtain crude product, purifying the crude product by conventional methods to obtain pure 3-sulfanyl cyclic ketones of general formula 3. In one of the embodiments of the present invention the cyclic enone may be of the general formula 2 wherein, A may be methylene or ethylene, R may be Hydrogen or methyl 7-heptanoate, R1 may be hydrogen, hydroxy, ter-butyldimethylsilyloxy, triethylsilyloxy or trimethylsilyloxy In another embodiment the organic solvent used for dissolving the enone of the formula 2 may be chlorinated solvent such as chloroform, dichloromethane, carbontetrachloride, and alcohol such as methanol or ethanol. Preferably chloroform In another embodiment the thiol used may be of the formula 1 may be selected from 2-mercaptoethanol, 4-chlorothiophenol, 4-methylthiophenol, l-(3-chlorophenyloxy)-3-sulfanyl-2-propanol, l-(4-methoxyphenyloxy)-3-sulfanyl-2-propanol, l-(l-naphthyloxy)-3-sulfanyl-2-propanol or l-(2-naphthyloxy)-3-sulfanyl-2-propanol In another embodiment the x type zeolite catalyst may be doped with lithium, potassium or cesium Preferably Li-X-type zeolite. In yet another embodiment the dehydrating agent used may be sodium sulfate or magnesium sulfate. In a feature of the present invntion the crude products of the formula 3 are purified using column chromatography with silica gel as an adsorbent and petroleum ether : ethyl acetate as an eluting solvent system to achieve 50- 90% yield of the pure isolated product. Process of preparation of compounds of formula 3 is discribed and claimed in our copending application No. NF-374/99. The process of the present invention is described by the following examples, which are illustrative only and should not be considered as limit to the socpe of the invention in any manner. Example 1 A solution of 2-cyclohexenone (96 mg. 1.0 mmol) and l-(l-naphthyloxy)-3-sulfanyl-2-propanol (234mg, 1.0 mmol) in dry methanol (5 ml) was stirred at 0 °C under inert atmosphere (maintained by using nitrogen or argon gas filled in balloon), x-type zeolite doped with lithium (20% by weight of enone) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 24 hr (monitored by TLC). The catalyst was removed by filtration and washed with methanol (2 ml). The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator. The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents) to collect pure 3-[2-hydroxy-3(l-naphthyloxy)]-l-cyclohexanone (239mg. 72.4 %) the product was confirmed by spectroscopic methods. Example - 2 A solution of 2- cyclohexenone (96 mg, 1.0 mmol) and 4-chlorothiophenol (144.5mg, 1.0 mmol) in methanol (3 ml) was stirred at 0 -5°c under inert atmosphere (maintained by using nitrogen or argon gas filled in balloon), x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 28 hr (monitored by TLC). The catalyst was removed by filtration and washed with methanol (2 ml). The organic filtrate was concentrated to dryness under reduced pressure using rotary evaporator The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents) to collect pure 3-(4-chlorophenylsulfanyl)-l-cyclohexanone (197 mg, 82 % ). The product was confirmed by spectroscopic methods Example - 3 A solution of 2-cyclohexenone (96mg, 1.0. mmol) and 4-methylthiophenol (124 mg, 1.0 mmol) in dry methanol (3 ml) was stirred at 0 °c under inert atmosphere (maintained by using nitrogen or argon gas filled in balloon), x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr The mixture was warmed to room temperature and stirred further for 30 hr (monitored by TLC). The catalyst was removed by filtration and washed with methanol (2 ml). The filtrate was concentrated to dryness under reduced pressure using rotary evaporator The crude residue was purified by a column of silica gel (using petroleum ether ethyl acetate as eluents) to collect pure 3-(4-methylphenylsulfanyl)-l-cyclohexanone ( 178 2 mg, 81% ). The product was confirmed by spectroscopic methods Example - 4 A solution of 2-cyclohexenone (96mg, 1.0. mmol) and 2-mercaptoethanol (78 mg, 10 mmol) in dry methanol (3 ml) was stirred at 0 °C under inert atmosphere (maintained by using nitrogen or argon gas filled in balloon), x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 28 hr (monitored by TLC) The catalyst was removed by filtration and washed with methanol (2 ml). The filtrate was concentrated to dryness under reduced pressure using rotary evaporator. The crude residue was purified by a column of silica gel (using petroleum ether ethyl acetate as eluents) to collect pure 3-(2-hydroxyethylsulfanyl)-l-cyclohexanone ( 130. mg, 75% ) The product was confirmed by spectroscopic methods Example - 5 A solution of 4-hydroxy-cyclopent-2-enone (98 mg, 1.0. mmol) and l-(l-naphthyloxy)-3-sulfanyl-2-propanol (468 mg, 2.0 mmol) in dry chloroform (2 ml) was stirred at 0 °c under inert atmosphere (maintained by using nitrogen or argon gas filled in balloon), x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 24 hr (monitored by TLC) The catalyst was removed by filtration and washed with chloroform (2 ml). The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced, pressure using rotary evaporator. The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents) to collect pure 3-hydroxy-4-[2-hydroxy-3-(l- naphthyloxy)propylsulfanyl]-1-cyclopentanone ( 265.6 mg, 80% ) The product was confirmed by spectroscopic methods Example - 6 A solution of 4-hydroxy-cyclopent-2-enone (98 mg, 10. mmol) and l-(2-naphthyloxy)-3-sulfanyl-2-propanol (468 mg, 2.0 mmol) in dry chloroform (2 ml) was stirred at 0 °c under inert atmosphere, x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 24 hr (monitored by TLC). The catalyst was removed by filtration and washed with chloroform (2 ml). The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator. The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents) to collect pure 3-hydroxy-4-[2-hydroxy-3-(2-naphthyloxy)propylsulfanyl]-l-cyclopentanone ( 262.3 mg, 79% ). The product was confirmed by spectroscopic methods Example - 7 A solution of 4-hydroxy-cyclopent-2-enone (98 mg, 1.0. mmol) and l-(4-methoxyphenyloxy)-3-sulfanyl-2-propanol (428 mg, 2.0 mmol) in dry chloroform (2 ml) was stirred at 0 °c under inert atmosphere, x-type zeolite doped with lithium ( 20 % by "t weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr The mixture was warmed to room temperature and stirred further for 24 hr (monitored by TLC). The catalyst was removed by filtration and washed with chloroform (2 ml). The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator. The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents) to collect pure 3-hydroxy-4-[2-hydroxy-3-(4-methoxyphenoxy)propylsulfanyl]-l-cyclopentanone ( 250 mg, 79% ). The product was confirmed by spectroscopic methods. Example - 8 A solution of 4-hydroxy~cyclopent-2-enone (98 mg, 1.0. mmol) and l-(3-chlorophenyloxy)-3-sulfanyl-2-propanol (437 mg, 2.0 mmol) in dry chloroform (2 ml) was stirred at 0 °c under inert atmosphere, x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 24 hr (monitored by TLC). The catalyst was removed by filtration and washed with chloroform (2 ml) The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents) to collect pure 3-hydroxy-4-[2-hydroxy-3-(4-chlorophenoxy)propylsulfanyl]-l-cyclopentanone ( 160 mg, 50% ) The product was confirmed by spectroscopic methods. Example - 9 A solution of 4-tertiary-butyldimethylsilyioxy -cyclopent-2-enone (212mg, 1.0. mmol) and (l-(l-naphthyloxy)-3-sulfanyl-2-propanol (702 mg, 3.0 mmol) in dry chloroform (2 ml) was stirred at 0 °c under inert atmosphere (as above), x-type zeolite doped with lithium (20 % by weight of enone) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 24 hr (monitored by TLC) The catalyst was removed by filtration and washed with chloroform (2 ml) The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator. The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents) to collect pure 3-tert-butyldimethylsilyloxy-4-[2-hydroxy-3-(l-naphthyloxy)propylsulfanyl]-l-cyclopentanone (290 mg, 65%) The product was confirmed by spectroscopic methods. Example -10 A solution of 4-tertiary-butyldimethylsilyloxy -cyclopent-2-enone (2l2mg, 1.0 mmol) and (l-(2-naphthyloxy)-3-sulfanyl-2-propanol (702 mg, 3.0 mmol) in dry chloroform (2 ml) was stirred at 0 °c under inert atmosphere, x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr The mixture was warmed to room temperature and stirred further for 24 hr (monitored by TLC) The catalyst was removed by filtration and washed with chloroform (2 ml). The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator The crude residue was purified by a column of silica gel (using petroleum ether ethyl acetate as eluents) to collect pure 3-tert-butyldimethylsilyloxy-4-[2-hydroxy-3-(2-naphthyloxy)propylsulfanyl]-1 -cyclopentanone (310 mg, 69%). The product was confirmed by spectroscopic methods Example -11 A solution of 4-tertiary-butyldimethylsilyloxy -cyclopent-2-enone (212mg, 1.0. mmol) and (l-(4-methoxyphenyloxy)-3-sulfanyl-2-propanol (642 mg, 3.0 mmol) in dry chloroform (2 ml) was stirred at 0 °c under inert atmosphere, x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr The mixture was warmed to room temperature and stirred further for 28 hr (monitored by TLC). The catalyst was removed by filtration and washed with chloroform (2 ml). The organic nitrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator. The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents) to collect pure 3-tert-butyldimethylsilyloxy-4-[2-hydroxy-3-(4- methoxyphenoxy)propylsulfanyl]-l-cyclopentanone (274.68 mg, 63%) The product was confirmed by spectroscopic methods 13-Thiaprostaglandin analogues Example -12 A solution of methyl 7-(3-hydroxy-5-oxocyclopent-2-enyl) heptanoate (120 mg, o.5 mmol) and (l-(l-naphthyloxy)-3-sulfanyl-2-propanol (234 mg, 10 mmol) in dry chloroform (1 ml) was stirred at 0 -5°c under inert atmosphere (maintained by using nitrogen or argon filled ballooon), x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 48 hr (monitored by TLC). The catalyst was removed by filtration and washed with chloroform (2 ml). The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents) to collect pure methyl 7-{3-hydroxy-2-[2-hydroxy-3-(l- naphthyloxy)propylsulfanyl]-5-oxocyclopentyl}heptanoate (330 mg, 70 %) The product was confirmed by spectroscopic methods Example -13 A solution of methyl 7-(3-hydroxy-5-oxocyclopent-2-enyl) heptanoate (120 mg, o.5. mmol) and (l-(2-naphthyloxy)-3-sulfanyl-2-propanol (234 mg, 1.0 mmol) in dry chloroform (1 ml) was stirred at 0 °c under inert atmosphere (maintained by using nitrogen or argon filled ballooon), x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 48 hr (monitored by TLC). The catalyst was removed by filtration and washed with chloroform (2 ml). The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator The crude residue was purified by a column of silica gel (using petroleum ether . ethyl acetate as eluents) to collect pure 7-{3-hydroxy-2-[2-hydroxy-3-(2-naphthyloxy)propylsulfanyl]-5-oxocyclopentyl}heptanoate (250 mg, 53 %). The product was confirmed by spectroscopic methods. Example -14 A solution of methyl 7-(3-hydroxy-5-oxocyclopent-2-enyl) heptanoate (120 mg, o.5. mmol) and (l-(4-methoxyphenyloxy)-3-sulfanyl-2-propanol (428 mg, 2.0 mmol) in dry chloroform (2 ml) was stirred at 0 °c under inert atmosphere (maintained by using nitrogen or argon filled ballooon), x-type zeolite doped with lithium ( 20 % by weight of enone ) was added and the mixture was stirred at the same temperature for 2 hr. The mixture was warmed to room temperature and stirred further for 40 hr (monitored by TLC). The catalyst was removed by filtration and washed with chloroform (2 ml). The organic filtrate was washed with water followed by brine, dried over sodium sulfate and concentrated to dryness under reduced pressure using rotary evaporator. The crude residue was purified by a column of silica gel (using petroleum ether : ethyl acetate as eluents)to collect pure 7-{3-hydroxy-2-[2-hydroxy-3-(4-methoxuphenoxy)propylsulfanyl]-5-oxocyclopentyl} heptanoate product ( 295 mg, 65 % ) The product was confirmed by spectroscopic methods. BIOLOGICAL ACTIVITY : Thiaprostaglandins are prostaglandin analogs in which the trans double bond at C13-C14 in natural prostaglandin F2oe is replaced by sulfur Such sulfur analogs are known for their luteolytic activity ( veterinary ) in the literature. For example, prosolvin is presently used as lutenizing hormone in cattle breeding. The thiaprostaglandin analogs prepared and included in this specification are expected to possess similar biological activity. ADVANTAGES: Thiaprostaglandins can be readily prepared by our process using zeolite catalysts which can be removed by filtration, reused and recycled. This process provides cheaper methodology of preparing biologically important compounds. Thiaprostaglandins are chemically and biologically stable analogs of naturally occurring prostaglandins therefore may be advantageous provided their biological activity is comparable which is yet to be explored. We claim : Novel 3-sulfanyl cyclic ketones having the general formula 3 of the drawing accompanying the specification wherein; A is methylene or ethylene, R may be hydrogen or methyl-7-heptanoate, R1 may be hydrogen, hydroxyl, ter-butyldimethylsilyloxy, triethysilyloxy, or trimethylsilyloxy; and R2 may be 2-hydroxyethylsulfanyl, 2-hydroxy-3-(4-chloro or methoxyphenyloxy)propylsulfanyl, 2-hydroxy-3-(1-naphthyloxy)propyl-sulfanyl or 2-hydroxy-3-(1-naphthyloy)propyl-sulfanyl or 2-hydroxy-3-(2-naphthyloxy) propylsulfanyl. Novel 3-sulfanyl cyclic ketone as claimed in claim 1 have following structure, (Structure Removed) 3. Novel 3-sulfanyl cyclic ketone as claimed in claim 1 have following formula (Formula Removed) 4. Novel 3-sulfanyl cyclic ketone as claimed in claim 1 have following formula (Formula Removed) Wherein R=H or TBDMS 5. Novel 3-sulfanyl cyclic ketone as claimed in claim 1 have following formula (Formula Removed) Wherein R=H or TBDMS 6. Novel 3-sulfanyl cyclic ketone as claimed in claim 1 have following formula (Formula Removed) Wherein R=H or TBDMS 7. Novel 3-sulfanyl cyclic ketone as claimed in claim 1 have following formula (Formula Removed) 8. Novel 3-fulfanyl cyclic ketone as claimed in claim 1 have following formula (Formula Removed) Wherein R=H or TBDMS 9. Novel 3-sulfanyl cyclic ketone as claimed in claim 1 have following formula (Formula Removed) Wherein R=H or TBDMS 10. Novel 3-sulfanyl cyclic ketones substantially as herein described with reference to the examples.

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