CA1335669C - 2,3-epoxycyclopentanones - Google Patents

Abstract

2,3-Epoxycyclopentanones are described having substituents in the 4-position or in both 4- and 5-positions. When both 4-and 5-positions are substituted, the 4-substituent is a substituted or unsubstituted aliphatic hydrocarbon group, and the 5-substituent is a hydroxyl- or carboxyl-containing group. When the 4-position only is substituted, one 4-substituent is hydroxyl or protected hydroxyl, and the second 4-substituent is a substituted or unsubstituted aliphatic hydrocarbon group. These compounds have anti-tumor or bone formation acceleration activity, or are intermediates for preparing such compounds.

Description

~ 133~69 This application is a divisional application of Serial No.
597,198, filed April 19, 1989.
BACKGROUND OF THE INVENTION
1. Field of the Invention The present invention relates to novel 2-substituted-2-cyclopentanones. More specifically, the present invention relatesto2-substituted-2-cyclopentenoneshavingpharmacological activities such as an excellent anti-tumor activity, and an excelent bone formation acceleration activity, and to an anti-tumor agent and a bone formation accelerator.

2. Description of the Related Art Prostaglandins are compounds having specific biological activities such as platelet aggregation inhibitory activities and hypotensive activities, and are naturally occurring substances which are useful as therapeutical agents for peripheral circulatory organ system diseases in current medical treatments.
Among these prostagIandins, prostagl~n~; n~ A are known to have a double bond in the cyclopentane ring; for example, prostaglandin A~ is considered to be a medicament having hypotensive activities (see E.J. Corey et al., J. Amer. Chem.
Soc., 95, 6831, 1973).
Also, since prostaglandins A inhibit potential DNA
synthesis, the possibility of using prostaglandins A as an anti-tumor agent has been reported (see Biochem. Biophys. Res.
Commun., 87, 795, 1979; W.A. Turner et al., Prostaglandins and Cancer: First International Conference ~305.1982).
European Une~;ned Published Patent Publication No. 0106576 (published on April 25, 1984), disclosed 4,5-substituted 2-cyclopentenones including prostaglandins A, among which are 5-alkylidene-4-substituted-2-cyclopentenones represented by the formula:
O
~ W

wherein W represents a hydrocarbon group having 1 to 12 carbon atoms which also may be substituted, and Y
represents a hydrocarbon group having 1 to 12 carbon atoms which also may be substituted and 5-(1-hydroxy-hydrocar~on)-4-substituted-2-cyclopentenones of the formula:

O OH

wherein W' and Y' are the same as W and ~, respectively.
Further, it is disclosed that these compounds are useful for the treatment of malignant tumors.
Also, European Un~m;ned Published Patent Publication No. 0131441 (published on January 16, 1985), disclosed 5-alkylidene-2-halo-4-substituted-2-cyclo-pentenones of the formula:

X ~Ra Rb wherein Ra represents a substituted or non-substituted hydrocarbon having 1 to 12 carbon atoms or a substituted or non-substituted phenyl group; Rb represents a substituted or non-substituted hydrocarbon having 1 to 12 carbon atoms; and X represents a halogen atom, and further, that these compounds are similarly effective for the treatment of malignant tumors.
Further, prostaglandins D and J different from prostaglandins A are ~nown to be useful as antitumor agents (Japanese Une~m;ned Patent Publication (Kokai) 58-216155 and proceedings of the National Academy of Sciences of the United States of America (Proc. Natl.
Acad. Sci. U.S.A.), 81, 1317 - 1321, 1984).

Also, prostaglandin analogues represented by the formula:
O OCOCH
_ ~ COOCH3 and isolated from coral produced in Okinawa [Okinawa soft coral: clavularia viridis] are known to have an antiinflammatory activity and antitumor activity as physiological activities thereof [see Kikuchi et al, Tetrahedron Lett., 23, 5171, 1982; Kobayashi et al, Tetrahedron Lett., 23, 5331, 1982; Masanori Fukushima, Cancer and Chemotherapy, 10, 1930, 1983).
Japanese Unexamined Patent Publication (Kokai) No. 59-59646 disclosed clavulon derivatives including the above natural products of the formula:
l R2 OCOCH3 CHa-CHb : CHc-CH-CH2CH2COOCH3 CH2--CHd--''' CHe--CH2CH2CH2CH2CH3 (R3)n R1 and R2 together represent a keto group, or one thereof is a hydrogen group and the other is hydroxy group~ R3 is a hydrogen atom or acetoxy group, n is O or 1, n being 0 when there is a double bond between the positions 8 and 12, a, b, c, d, and e are each 1 or 2, and the dotted line denotes a single bond or double bond between c and d, and that these compounds are useful as antiinflammatory agents.
Japanese Unexamined Patent Publication (Kokai) No. 59-184158 disclosed, as a compound having a similar antiinflammatory activity, culavulon derivatives of the formula:

OAc ,J~,~ CH-CH=CH-CH-CH2CH2COOCH3 7--CH2-CH=CH-CH2CH2CH2CH2CH20Ac OAc wherein Ac denotes an acetyl group.
Japanese Unexamined Patent Publication (Kokai) 10No. 60-4129 disclosed that the culavalon derivatives included in the above two formulae are useful as antitumor agents.
E. J. Corey et al synthesized the culavalon derivatives represented by the following formula:

(Journal of the American Chemical Society (J. Am. Chem.
Soc.), 106, 3384, 1984).
Nagaoka et al similarly synthesized culavulon derivatives represented by the following formula:
O ~ COOCH
~~~ ~ OcOCH3 (Tetrahedron Letters, vol. 25, No. 33, pages 3621 - 3624, 1984).
Further, recently, punaglandins 1 and 2 represented by the formula:

O OAc OAc ~L ~ COOME

C \~ OAc OH

and the formula:
O OAc OAc ~ ~ COOME
~ l Cl-\~ OAc \'~\ /\
OH

~were isolated from Telesto riisei growing on a ship's bottom at Oaf Island (P.J. Sherer et al., J. Amer. Chem.
Soc. 107 2976 (1985).
2n Also, published PCT Patent Application No. w085-03706 (publication date: August 29, 1985) disclosed punaglandins represented by the following formula:
O OR
~ COORl Cl \\ ¦ OR
~4\`/'== " /~=='\~
. R O
wherein R1 represents a hydrogen atom, C1 - C10 an alkyl group or one equivalent cation, R , R , R may be the same or different, and each represents a hydrogen atom . or C2 - C10 acyl group, and the representation _ _ denotes a single bond or double bond, and that these punaglandins are useful for the therapy of malignant tumors.

Masanori Fukushima et al reported that the compounds of the following formula included in the above formula:
O AcO OAc ~ ~ COOC~3 Cl ~ ~

OH

have an antitumor activity (see ~asanori Fukushima et al collected gists of the 43rd Meeting of Japanese Society of Cancer, p. 258, 1984).
Furthér, Japanese Unexamined Patent Publi-cation (Kokai) No. 62-96438 disclosed 4-hydroxy-2-cyclopentenones which are culavulon analogues and punaglandin analogues of the formula:
A B

X~J ~R
e~ R2 oR3 - wherein X represents a hydrogen atom or a halogen atom;
A and B represent a combination of A which is a hydrogen atom and B which is a hydroxyl group or A and B are bonded mutually to represent one bonding arm; R1 represents a substituted or non-substituted alkyl group, and an alkenyl group or alkynyl group having 1 to 10 carbon atoms; R2 represents a substituted or non-substituted alkyl, alkenyl or alkynyl group having 1 to 10 carbon atoms; and R3 represents a hydrogen atom or a protective group for a hydroxyl group; with the proviso that R2 cannot be 2-octenyl, 8-acetoxy-2-octenyl or 2,5-octadienyl and that these compounds are useful for the therapy of malignant tumors.
Furthermore, the bone metabolism of an average healthy human is considered to be valid when a good balance is maintained between repeated bone resorption with an osteoclast and bone formation with an osteoblast, and when this balance between bone resorption and bone formation is disturbed, diseases such as osteoporosis or osteomalacia may occur. As the therapeutical agents for such bone diseases, active type vitamin preparations, calcitonin preparations, diphosphonic acid preparations, estrogen preparations and calcium preparations may be employed, but although many of these preparations have been reported to inhibit bone resorption, etc., none have clearly manifested an effect of accelerating bone formation. Further, the effects of these preparations are uncertain, and accordingly, there is a strong demand for the development of a drug which causes an acceleration of bone formation with osteoblast, without uncertainty about the effects thereof.
Ko~h;h~ra et al. found that prostaglandin D2 has a calcification accelerating activity on human osteoblast, as reported in the Biochemical Society of Japan (Collected Gists, p. 767, 1988) thought to be caused by the activity of 1Z_ prostaglandin J2 formed by a decomposition of prostaglandin D2.
Nevertheless, a bone acceleration activity of the 2-substituted-2-cyclopentanones is not known.
SUMMARY OF THE INVENTION
Accordingly, an object of the present invention is to obviate the above-mentioned problems in the prior art and to provide novel 2-substituted-2-cyclopentenones, namely 2-cyclopentenones substituted at the 2-position with a sulfur atom in the form of a thioether and to provide novel 2,3-epoxycyclopentanones substituted in the 4-, or 4- and 5-positions.
Another object of the present invention is to provide such 2~substituted-2-cyclopentenones having a remarkable anti-tumor activity.
A further object of the present invention is to provide such .

2-substituted-2-cyclopentenones having a remarkable bone formation accelerating activity.
A still further object of the present invention is to provide a process for producing 2-substituted-2-cyclopentenones of the present invention.
Other objects and advantages of the present invention will be apparent from the description set forth hereinbelow.
The invention includes 2,3-epoxycyclopentanones represented by the formula (iv-a-10): 0 OH

~ R
O ~ a-10 wherein R2 represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 10 carbon atoms, in which the substituent of the substituted group is selected from -CooR5l wherein R5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or one equivalent cation; -oR6~ wherein R6 represents a hydrogen atom, an acyl group having 2 to 7 carbon atoms, a tri(C1-C7)hydrocarbonsilyloxy group, a methoxymethyl group, a 1-ethoxyethyl group, a 2-methoxy-2-propyl group, a 2-ethoxy-2-propyl group, a 2-methoxyethoxy-methyl group, a tetrahydropyran-2-yl group, a tetrahydrofuran-2-yl group, a 6,6-dimethyl-3-oxa-2-oxo-bicyclo[3.1.0]-hexan-4-yl group, an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1-C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1-C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an --- 8a -acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1-C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms;~and R34 represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 10 carbon atoms, wherein the substituent of the substituted group is selected from -CooR5~ wherein R5 is a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a one equivalent cation; -oR6, wherein R6 is a hydrogen atom, an acyl group having 2 to 7 carbon atoms, a tri(C1-C7)hydrocarbonsilyl group, a group which forms an acetal bond with the oxygen atom to which R6 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1-C7) hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; or an alicyclic hydrocarbon group which may be substituted with a halogen atom, hydroxyl group, a tri(C1 -C7) hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms.

- 8b -The invention also includes 2,3-epoxycyclopentanones represented by the formula (iv-b-10):
o ~ --- (IV-~-10 O \ \ R
OR~0 wherein R34 represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 10 carbon atoms, wherein the substituent of the substituted group is selected from -CooR5~
wherein R5 is a hydrogen atom, an alkyl group having 1 to lO
carbon atoms or a one equivalent cation; -oR6, wherein R6 is a hydrogen atom, an acyl group having 2 to 7 carbon atoms, a tri (C1-C7) hydrocarbonsilyl group, a group which forms an acetal bond with the oxygen atom to which R6 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1-C7) hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; or an alicyclic hydrocarbon group which may be substituted with a halogen atom, hydroxyl group, a tri(C1-C7) hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; and R40 represents a hydrogen atom or a 13~56~9 - 8c -protecting group of the protected hydroxyl group.
As part of the related subject matter there is provided a 2~substituted-2-cyclopentenones represented by the formula (I):
B A

R1-S ~ R2 .... (I) ()n ~ R3 X

wherein A is a hydroxy group or (I )m -b-Rl and B is a hydrogen atom or A and B are bonded together to form one bonding arm;
R1 represents a substituted or unsubstituted hydrocarbon group having 1 to 10 carbon atoms;
RZ represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 10 carbon atoms;
R3 represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 10 carbon atoms; wherein, when R3 is a single bond bonded to the cyclopentene skeleton, X represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group; and when R3 is a double bond bonded to the pentene skeleton, X
represents a bonding arm constituting a part of said double bond;
and m and n independently represent 0, 1 or 2.

- 9 - 133~6~9 In the above formula (I), A and B represent a combination of A which is a hydroxyl group or ()m -S-R
and B is a hydrogen atom or A and B are bonded together to represent one bonding arm. That is, when A is a hydroxyl group and B is a hydrogen group, the above formula ~I) represents 2-substituted-2-cyclopentenones represented by the following formula (I-b'):
OH
O H
Rl_S ~ R2 .... (I-b') ()n ~ R3 wherein Rl, R2, R3, X and n are as defined above; when A is ()m -S-R
and B is a hydrogen atom, the above formula (I) represents 2-substituted-2-cyclopentanones represente,d by the following formula 5 I-b"):
( lol ) m S-R
o H l R1_s ~ R2 .... (I-b") ()n ~ R3 X

wherein Rl, R2, R3, X, m and n are as defined above;
when A and B are bonded together to represent one bonding arm, the above formula (I) represents 2-substi-tuted-2-cyclopentenones represented by the following formula (I-a):

- - 10 - 13~56 6g Rl_s ~ ~ r~R2 .... (I-a~

( O ~ l\

wherein R1, R~, R3, X and n are 2S defined above, and the representation - denotes that the substituent bonded to the double bond is in an E-configuration or a 1~ Z-configuration or a mixture thereof at any desired ratio.
In the above formula (I), R1 represents a substi-tuted or non-substituted hydrocarbon group having 1 to 10 carbon atoms. Examples of the non-substituted hydrocarbon group having 1 to 10 carbon atoms include alkyl groups such as methyl, ethyl, propyl, isopropyl butyl, isobutyl, s-butyl t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl and the like; aralkyl groups such as benzyl, phenetyl, phenylpropyl, phenylbutyl and the like; or aryl groups such as phenyl, p-tolyl, 1-naphthyl, 2-naphthyl groups, and the like. The hydrocarbon group may be substituted with a plural dlfferent substitution groups. The substituents on such hydrocarbon groups include a hydroxyl group; tri(Cl - C7)hydrocarbonsilyloxy groups such as trimethylsilyloxy, triethylsilyloxy, t-butyldimethylsilyloxy, t-butyldiphenylsilyloxy, and tribenzylsilyloxy groups; halogen atoms such as fluorine, chlorine, and bromine; alkoxy groups such as 3~ methoxy and ethoxy groups; acyloxy groups such as acetyloxy and propanoyl groups; and dCyl groups such as acetyl and propionyl groups; alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, and propoxycarbonyl;
and carboxyl group. Preferably R1 represents alkyl groups having 1 to 5 carbon atoms such as methyl, ethyl, propyl, butyl, and pentyl groups, and phenyl groups, particularly preferably, a methyl group.

~ - 11 133S6~

In the above formula (I~, m and n are the same or different and represent 0, 1 or 2. The substituent R1-S- or R1-S-(O)m (O)n represents a hydrocarbonthio group when m or n is 0, ahydrocarbonsulfinyl group when m or n is 1, and a hydrocarbonsulfonyl aroup when m or n is 2.
In the above formula (I), R2 represents a substi-tuted or non-substituted aliphatic hydrocarbon group 1~ having 1 to 10 carbon atoms. Examples of the non-substituted aliphatic hydrocarbon group having 1 to 10 carbon atoms include alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, 3,7-dimethyloctyl, nonyl or decyl groups; alkenyl groups such as vinyl, 1-propenyl 2-propenyl, 1-butenyl, 1,3-butadienyl, 2-~utenyl, 1-pentenyl, 2-pentenyl, 1-hexenyl, 2-hexenyl, 1,5-hexadienyl, 3-hexenyl, 1-heptenyl, 1-octenyl, 1,7-octadienyl, 1-nonenyl or 1-decenyl groups; and alkynyl groups such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 3-buten-1-ynyl, 2-butynyl, 1-pentynyl, 2-pentynyl, 1-hexynyl, 2-hexynyl, 5-hexen-1-ynyl, 3-hexynyl~ heptynyl, 1-octynyl, 7-octen-1-ynyl, 1-nonynyl or l-decynyl groups. The aliphatic hydrocarbon group may be substituted with plural different substitution groups. The substitutent on such aliphatic hydrocarbon groups include~ -CooR5 (wherein R5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or one equivalent 3~ cation); _oR6 (wherein R6 represents a hydrogen atom; an acyl group having 2 to 7 carbon atoms; a tri(Cl - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R6 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl ~ - 12 - 133S669 , group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group a tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 ~o 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 -C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms~ Examples of R in -CooR5 include a hydrogen atom; alkyl groups having 1 to 10 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl, pentyl, neopentyl, hexyl, heptyl, octyl, nonyl or decyl groups; one equivalent cation such as cations of ammonium, tetramethyl ammonium, monomethyl ammonium, dimethyl ammonium, trimethyl ammonium, benzyl ammonium, and phenetyl ammonium, or a morpholinium cation, piperidinium cation or Na , K , 1/2Ca 1/2Mg2 , 1/2Zn , 1/3A13 . Preferably, R5 represents a hydrogen atom, methyl group, and ethyl group.
Examples of R6 in _oR6 include a hydrogen atom;
3 n acyl groups having 2 to 7 carbon atoms such as acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, hexanoyl, heptanoyl, and benzoyl groups; tri(Cl - C7)-hydrocarbonsilyl groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenyl-silyl, and tribenzylsilyl groups; and groups which forman acetal bond together with the oxygen atom to which R6.
is bonded such as methoxymethyl, 1-ethoxyethyl, ~ - 13 - 1335669 2-methoxy-2-propyl, 2-ethoxy-2-propyl, 2-me~hoxyet;~oxy-methyl, te~rahydropyran-2-yl, tetrahydrofuran-2-yl, and 6~6-dimethyl-3-oxa-2-oxO-biCyClO[3.l.o]hexan-4-yl groups. Examples of the aromatic hydrocarbons which may be substituted with a halogen atom, a hydroxyl group, a tri(Cl - C7)hydrocarbonsilyloxy group, a carboxyl sroup, an acyloxy group having 2 to 7 carbon atoms, an acy' group having 2 to 7 carbon atoms an alkoxycarbonyl group having 2 to 5 carbon atoms, or an alkyl group having 1 to 4 carbon atoms are phenyl, 1-naphthyl, 2-naphthyl, and 1-anthranyl. Examples of the substituent are 2 halogen atom such as fluorine, chlorine, and bromine; a hydroxyl group; tri(C1 - C7)hydrocarbonsilyloxy groups such as trimethylsilyloxy, triethylsililoxy, t-butyldimethylsilyloxy, t-butyldiphenylsililoxy, and tribenzylsilyloxy groups; a carboxyl group; an acyloxy groups such as acetoxy, propionyloxy, butyryloxy, isobutyryloxy, valeryloxy, isovaleryloxy, hexanoyloxy, heptanoyloxy, and benzoyloxy groups; acyl groups sucn as acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, hexanoyl, heptanoyl, and benzoyl groups;
alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, and s-butoxycarbonyl groups; alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, and t-butyl groups;
and alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, and t-butoxy groups. Particularly preferably, R~ represents a hydrogen atom, acetyl group, trimethylsilyl group, t-butyldimethylsilyl group, tetrahydropiran-2-yl group, and phenyl group.
Examples of the aromatic hydrocarbon group and the substituent, when the substituent group of R is an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms, are those as mentioned in the case of R6.
Preferable substituents are phenyl, 3,4-dimethoxyphenyl, and 4-methoxycarbonylphenyl.
When R2 is an alicyclic hydrocarbon group having 4 to 10 carbon atoms which may be substituted with a halogen atom, a hydroxyl group, tri(C1 - C7)-hydrocarbonsilyloxy group, a carboxyl group, an acyloxygroup having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms, examples of such an alicyclic group are cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, 4-cyclohexenyl, cycloheptyl, cyclooctyl, bicyclo[4.4.0]decane-2-yl groups and examples of the substituent are halogen atoms such as ~luorine, chlorine, and bromine; a hydroxyl group; tri(C1 - C7)hydrocarbonsilyloxy groups such as trimethylsililoxy, triethylsililoxy, t-butyldimethylsilyloxy, t-butyldiphenylsililoxy, and tribenzylsilyloxy groups; a carboxyl group; acyloxy groups such as acetoxy, propionyloxy, butyryloxy, isobutyryloxy, valeryloxy, isovaleryloxy, hexanoyloxy, heptanoyloxy, and benzoyloxy groups; acyl groups such as acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, hexanoyl, heptanoyl, and benzoyl groups;
alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, and s-butoxycarbonyl groups; alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl groups; and alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, and t-butoxy ~ - 15 - 1335669 groups. Particularly preferably, 4-hydroxycyclohexyl, 3,5-diacetoxycyclohexyl, cyclopentyl, and 3-ethylcyclopentyl can be exemplified.
In the above ~ormula (I), R3 represents a substi-tuted or non-substituted aliphatic hydrocarbon group having 1 to 10 carbon atoms, and when R3 is bonded through a single bond to the cyclopentene skeleton, X
represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group, and when R3 is bonded through a double bond to the cyclopentene skeleton, X represents a part of said double bond. More specifically, when R3 is bonded through a single bond to the cyclopentene skeleton, the above formula (I) represents 2-substi-tuted-2-cyclopentenones represented by the following formula (I'):
B A
O - ,~
R1 S ~ R2 ... (I') ( )n ~ R34 Il X

wherein A, B, R1, R2 and n are as defined above; R3 represents a substituted or non-substituted aliphatic hydrocarbon group having 1 to 10 carbon atoms; X
represents a hydrogen atom, hydroxyl group or a protected hydroxyl group]; when R3 is bonded through a double bond to the cyclopentene skeleton and X
represents a bond in said double bond, the above formula (I) represents 2-substituted-2-cyclopentenones represented by the following formula (I"):

B A
O
R1-S ~ ~ R2 ... (I") ()n ~ ~ R33 wherein A, B, R , R , n and the representation ~~v are as defined above; R33 represents a hydrogen atom or a substituted or non-substituted aliphatic hydrocarbon group having 1 to 9 carbon atoms.
R3 in the above formula (I') represents a substituted or non-substituted aliphatic hydrocarbon group having 1 to 10 carbon atoms, and examples of such R34 include the same groups as mentioned above for R2, also including the substituents.
Xl in the above formula (I') represents a hydrogen atom, hydroxyl group or a protected hydroxyl group, and examples of the protected hydroxyl group include alkoxy groups such as methoxy, ethoxy, propoxy, and isopropoxy;
tri(C1 - C7)hydrocarbonsilyloxy groups such as trimethylsilyloxy, triethylsilyloxy, t-butyldimethyl-silyloxy, t-butyldiphenylsilyloxy, and tribenzylsilyloxy groups; acetal groups such as methoxymethoxy, l-ethoxy-ethoxy, 2-methoxyethoxymethoxy, and tetrahydropyran-2-yloxy groups; and acyloxy groups such as acetoxy, propionyloxy, and butyryloxy groups. Preferably, X
represents a hydrogen atom, hydroxyl group, methoxy group, ethoxy group, trimethylsilyloxy group, and acetoxy group.
R33 in the above formula (I") represents a substituted or non-substituted aliphatic hydrocarbon group having 1 to 9 carbon atoms and examples of the substituent for such R33 include the same substituents as mentioned above for R2. Examples of the non-substituted aliphatic hydrocarbon group having 1 to 9 carbon atoms of R33 include alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl or nonyl groups; alkenyl groups such as vinyl, l-propenyl, 2-propenyl, l-butenyl, 1,3-butadienyl, 2-butenyl, l-pentenyl, 2-pentenyl, l-hexenyl, 2-hexenyl, 1,5-hexadienyl, 3-hexenyl, 1-heptenyl, 2,6-dimethyl-heptenyl, l-octenyl, 1,7-octadienyl or l-nonenyl groups;

- 17 _ 1335669 and alkynyl groups such zc ethynyl, l-propynyl, 2-propynyl, l-butynyl, 3-~uten-l-ynyl, 2-butynyl, l-pentynyl, 2-pentynyl, l-hexynyl, 2-hexynyl, 5-hexen-1-ynyl, 3-hexynyl, l-heptynyl, l-octynyl, 7-octen-l-ynyl S or 1-nonynyl groups.
Examples of 2-substituted-2-cyclopentenones represented by the above-mentioned formula (I) include the compounds set forth below.
(1) 2-methylthio-5-(l-hydroxy-6-methoxycarbonyl-l~ hexyl)-4-(3-t-butyldimethylsilyloxy-l-octenyl)-2-cyclo-pentenone (2) 2-methylthio-5-~1-hydroxy-6-methoxycarbonyl)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone (3) 2-methylsulfinyl-~-(l-hydroxy-6-methoxy-carbonyl-hexyl)-4-(3-hydr-xy-l-octenyl)-2-cyclopentenone (4) 2-methylsulfony'-5-(l-hydroxy-6-methoxy-carbonylhexyl)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone (5) 2-methylthio-5-~l-hydroxy-6-carboxyhexyl)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone 20(6) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-t-butyldimethylsilyloxy-l-octenyl)-2-cyclopentenone (7) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (8) 2-methylsulfiny7-5-(6-methoxycarbonylhexyli-dene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (9) 2-methylsulfonyl-5-(6-methoxycarbonylhexyli-dene)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone (10) ?-methylthio-S-(s-methoxycarbonylhexylidene)-4-(3-actetoxy-l-octenyl)-)-2-cyclopentenone 30(ll) 2-methylthio-5-(6-carboxyhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (l2) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(1-octenyl)-2-cyclopent~one (13) 2-methylsulfinyl-5-(6-methoxycarbonylhexyli-dene)-4-(l-octenyl)-2-cyclopentenone (14) 2-methylsulfonyl-5-(6-methoxycarbonylhexyli-dene)-4-(1-octenyl)-2-cyclopentenone ~ - 18 - 133~6~9 (~5) 2-methylthio-5-(6-carboxyhexylidene)-4-~1-octenyl)-2-cyclopentenone (16) 2-methylthio-5-(1-methylthio-6-methoxy-carbonylhexylidene)-4-(1-actenyl)-2-cyclopentenone (17) 2-methylsulfinyl-5-(1-methylsulfinyl-6-methoxycarbonylhexylidene)-4-~1-octenyl)-2-cyclo-pentenone (18) 2-methylsulfonyl-5-(1-methylsulfonyl-6-methoxycarbonylhexylidene)-4-~1-octenyl)-2-cyclo-1~ pentenone (19) 2-ethylthio-5-(1-hydroxy-6-methoxycarbonyl-hexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclo-pentenone.
(20) 2-ethylthio-5-(6-methoxycarbonylhexylidene).-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone (21) 2-ethylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (22) 2-ethylsulfinyl-5-(6-methoxycarbonylhexyli-dene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (23) 2-ethylsulfonyl-5-(6-methoxycarbonylhexyli-dene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (24) 2-ethylthio-5-(6-carboxylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (25) 2-phenylthio-5-(8-ethoxycarbonyloctylidene)-4-[3-(tetrahydropyran-2-yloxy)-1-octenyl]-2-cyclo-pentenone ~26) 2-phenylthio-S-(8-ethoxycarbonyloctylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (27) 2-phenylsulfinyl-5-(8-ethoxycarbonyloctyli-dene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (28) 2-phenylsulfonyl-5-(8-ethoxycarbonyloctyli-dene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (29) 2-phenylthio-5-(8-carboxyoctylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (30) 2-(5-methoxycarbonylpentylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-t-butyldimethylsily-loxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone ~ - 19 - 13356~9 (31) 2-(5-methoxycarbonylpentylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-hydroxy-3-cyclo-pentyl-l-propenyl)-2-cyclopentenone (32) 2-(5-methoxycarbonylpentylthio)-5-(6-methoxy-carbonyl-2-hexynylidene)-4-(3-t-butyldimethylsilyloxy-3--cyclopentyl-1-propenyl)-2-cyclopentenone (33) 2-(5-methoxycarbonylpentylthio)-5-(6-methoxy-carbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone (34) 2-(5-methoxycarbonylpentylsulfinyl)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclo-pentyl-1-propenyl)-2-cyclopentenone (35) 2-(5-methoxycarbonylpentylsulfonyl)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclo-pentyl-1-propenyl)-2-cyclopentenone (36) 2-(3-phenylpropylthio)-5-(1-hydroxy-6-methoxy-carbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-l-propenyl)-2-cyclopentenone (37) 2-(3-phenylpropylthio)-5-(1-hydroxy-6-methoxy-carbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone (38) 2-(3-phenylpropylthio)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-t-butyldimethylsilyloxy-3-cyclo-pentyl-1-propenyl)-2-cyclopentenone (39) 2-(3-phenylpropylthio)-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl~-2-cyclopentenone (40) 2-(3-phenylpropylsulfinyl)-5-(6-methoxy-carbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone (41) 2-(3-phenylpropylsulfonyl)-5-(6-methoxy-carbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone (42) 2-phenylthio-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone (43) 2-phenylthio-5-(6 methoxycarbonyl-2-hexynyli-~ _ 20 ~ 5 6 69 dene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclo-pentenone (44) 2-phenylsulfinyl-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone (45) 2-phenylsulfonyl-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone (46) 2-(6-methoxylnaphthyl-2-thio)-5-(1-hydroxy-6-1~ methoxycarbonyl-2-hexynyl)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone (47) 2-(6-methoxynaphthyl-2-thio)-5-(6-methoxy-carbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propen~l)-2-cyclopentenone (48) 2-(6-methoxynaphthyl-2-sul~inyl)-5-(6-methoxy-carbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2c~clopentenone (49) 2-(6-methoxynaphthyl-2-sulfonyl)-5-(6-methoxy-carbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopent~1-1-propenyl)-2-cyclopentenone (50) 2-(4-chlorophenylmethylthio)-5-(1-hydroxy-6-methoxycarbonyl-5-hexenyl)-4-(3-hydroxy-5-methyl-1-nonenyl)-2-cyclopentenoner (51) 2-(4-chlorophenylmethylthio)-5-(6-methoxy-~5 carbonyl-5-hexenylidene-4-(3-hydroxy-5-methyl-1-nonenyl)-2-cyclopentenone (52) 2-(4-chlorophenylmethylsulfinyl)-5-(6-methoxycarbonyl-5-hexenylidene)-4-(3-hydroxy-5-methyl-1--nonenyl)-2-cyclopentenone 3~ (53) 2-(4-chlorophenylmethylsulfonyl)-5-(6-methoxy-carbonyl-5-hexenylidene)-4-(3-hydroxy-5-methyl-1-nonenyl)-2-cyclopentenone (54) 2-ethylthio-5-(1-hydroxy-6-methoxy(carbonylhexyl)-4-[3-(tetrahydropyran-2-yloxy)-3-cyclohexyl-1-propenyll-2-cyclopentenone (55) 2-ethylthio-5-(6-methoxycarbonylhexylidene)-4-[3-(tetrahydropyran-2-yloxy)-3-cyclohexyl-1-propenyl]-2-cyclopentenone (56) 2-ethylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-2-cyclopentenone (57) 2-(4-methylphenylthio)-5-(1-hydroxy-3-phenyl-2-propenyl)-4-butyl-2-cyclopentenone (58) 2-(4-methylphenylthio)-5-(3-phenyl-2-pro-penylidene)-4-butyl-2-cyclopentenone (59) 2-(4-methylphenylsulfinyl)-5-(3-phenyl-2-propenylidene)-4-butyl-2-cyclopentenone (60) 2-(4-methylphenylsulfonyl)-5-(3-phenyl-2-propenylidene)-4-butyl-2-cyclopentenone (61) 2-methylthio-5-(1,4,7-trihydroxy-2-heptenyl)-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone (62) 2-methylthio-5-(1,4,7-trihydroxy-2-heptenyl)-4-~4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (63) 2-methylsulfinyl-5-(1,4,7-trihydroxy-2-heptenyl)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (64) 2-methylsulfonyl-5-(1,4,7-trihydroxy-2-heptenyl)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (65) 2-methylthio-5-(1-hydroxy-4,7-diacetoxy-2-heptenyl)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (66) 2-methylthio-5-(4,7-dihydroxy-2-heptenyli-dene)-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclo-pentenone (67) 2-methylthio-5-(4,7-dihydroxy-2-heptenyli-dene)-4-(4-phenoxybutyl)-4-methoxy-2-cyclopentenone (68) 2-methylthio-5-(4,7-dihydroxy-2-heptenyli-dene)-4-(4-phenoxybutyl)-4-ethoxy-2-cyclopentenone (69) 2-methylthio-5-(4,7-diacetoxy-2-heptenyli-dene)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (70) 2-methylthio-5-(4,7-diacetoxy-2-heptenyli-dene)-4-(4-phenoxybutyl)-4-acetoxy-2-cyclopentenone (71) 2-methylsulfinyl-5-(4,7-dihydroxy-2-heptenyli-dene)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopetenone (72) 2-methylsulfonyl-5-(4,7-dihydroxy-2-heptenyli-dene)-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone ~ - 22 - 133S6~9 (73) 2-methylthio-5-(4,7-dihydroxy-2-heptenyli-dene)-4-(4-phenoxybutylidene)-2-cyclopentenone (74) 2-methylsulfinyl-S-(4,7-dihydroxy-2-heptenyli-dene)-4-(4-phenoxybutylidene)-2-cyclopentenone (75) 2-methylsulfonyl-5-(4,7-dihydroxy-2-heptenyli-dene~-4-(4-phenoxybutylidene)-2-cyclopentenone (76) 2-methylthio-5-[1-hydroxy-3-(4-methoxy-carbonylcyclohexyl)propyl~-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (77) 2-methylthio-5-[3-(4-methoxycarbonylcyclo-hexyl)propylidene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclo-pentenone (78) 2-methylsul~inyl-5-~3-(4-methoxycarbonylcyclo-hexyl)propylidene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclo-pentenone (79) 2-methylsulfonyl-5-[3-(4-methoxycarbonylcyclo-hexyl)propylidene~-4-(4-phenoxybutyl)-4-hydroxy-2-cyclo-pentenone (80) 2-methylthio-5-[1-hydroxy-4-(4-methoxyphenyl)-butyl]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (81) 2-ethylthio-5-[4-(4-methoxyphenyl)butylidene]
4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (82) 2-methylsulfinyl-5-~4-(4-methoxyphenyl)butyli-dene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (83) 2-methylsulfonyl-5-r4-(4-methoxyphenyl)butyli-dene]-4-(4-phenoxybutyl)-4-hydroxy-2-cyclopentenone (84) 2-phenylthio-5-(1-hydroxyoctyl)-4-(4-phenoxy-butyl)-4-hydroxy-2-cyclopentenone (85) 2-phenylthio-5-octylidene-4-(4-phenoxybutyl)-3~ 4-hydroxy-2-cyclopentenone (86) 2-phenylsulfinyl-5-octylidene-4-(4-phenoxy-butyl)-4-hydroxy-2-cyclopentenone (87) 2-phenylsulfonyl-5-octylidene-4-(4-phenoxy-butyl)-4-hydroxy-2-cyclopentenone (88) 2-methylthio-5-(1-hydroxy-6-methoxycarbonyl-hexyl)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclopentenone ~ - 23 - 1335669 (89) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-~3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclo-pentenone (90) 2-methylsulfinyl-5-(6-methoxycarbonylhexyli-dene)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclopentenone (91) 2-methylsulfonyl-5-(6-methoxycarbonylhexyli-dene)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclopentenone (92) 2-methylthio-5-(1-hydroxy-6-methoxycarbonyl-hexyl)-4-(3,7-dimethyloctyl)-4-hydroxy-2-cyclopentenone (93) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3,7-dimethyloctyl)-4-hydroxy-2-cyclopentenone (94) 2-methylsulfinyl-5-(6-methoxycarbonylhexyli-dene)-4-(3,7-dimethyloctyl)-4-hydroxy-2-cyclopentenone (95) 2-methylsulfonyl-5-(6-methoxycarbonylhexyli-dene)-4-(3,7-dimethyloctyl)-4-hydroxy-2-cyclopentenone (96~ 2-methylthio-5-(1-hydroxy-6-methoxycarbonyl-hexyl)-4-(1-hexynyl)-4-hydroxy-2-cyclopentenone (97) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(1-hexynyl)-4-hydroxy-2-cyclopentenone (98) 2-methylsulfinyl-5-(6-methoxycarbonylhexyli-dene)-4-(1-hexynyl)-4-hydroxy-2-cyclopentenone (99) 2-methylsulfonyl-5-(6-methoxycarbonylhexyli-dene)-4-(1-hexynyl)-4-hydroxy-2-cyclopentenone (100) 2-methylthio-5-(l-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-4-hydroxy-2-cyclopentenone (101) 2-methylthio-5-(6-methoxycarbonyl-2-hexynyli-dene)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-4-hydroxy-2-cyclopentenone (102) 2-methylsulfinyl-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-4-hydroxy-2-cyclopentenone (103) 2-methylsulfonyl-5-(6-methoxycarbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclohexyl-1-propenyl)-4-hydroxy-2-cyclopentenone (104) 2-methylthio-5-(1-hydroxy-6-methoxycarbonyl-hexyl)-4-methyl-4-hydroxyl-2-cyclopentenone (105) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-methyl-4-hydroxyl-2-cyclopentenone (106) 2-methylsulfinyl-5-(6-methoxycarbonylhexyli-dene)-4-methyl-4-hydroxy-2-cyclopentenone (107) 2-methylsulfonyl-5-(6-methoxycarbonylhexyli-dene)-4-methyl-4-hydroxy-2-cyclopentenone (108) 2-methylthio-5-(1-hydroxy-6-methoxycarbonyl)-4-octyl-4-hydroxy-2-cyclopentenone (109) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-octyl-4-hydroxy-2-cyclopentenone (110) 2-methylsulfinyl-5-(6-methoxycarbonylhexyli-dene)-4-octyl-4-hydroxy-2-cyclopentenone (111) 2-methylsulfonyl-5-(6-methoxycarbonylhexyli-dene)-4-octyl-4-hydroxy-2-cyclopentenone (112) 2-methylthio-5-(6-carboxyhexylidene)-4-octyl-4-hydroxy-2-cyclopentenone (113) 2-(2-phenylethylthio)-5-[1-hydroxy-5-(acetoxy-methyl)-6-acetoxyhexyl]-4-(6-nonynyl)-4-hydroxy-2-cyclo-pentenone (114) 2-(2-phenylethylthio)-5-[5-(acetoxymethyl)-6-acetoxyhexylidene]-4-(6-nonynyl)-4-hydroxy-2-cyclo-pentenone (115) 2-(2-acetoxyethylthio)-5-(1-hydroxy-10-methoxydecyl)-4-benzyl-4-hydroxy-2-cyclopentenone (116) 2-(2-acetoxyethylthio)-5-(10-methoxydècyli-dene)-4-benzyl-4-hydroxy-2-cyclopentenone (117) 2-(3-acetylphenylmethylthio)-5-[1-hydroxy-4-(4-chlorophenoxy)butyl]-4-(1-octenyl)-4-hydroxy-2-cyclopentenone (118) 2-(3-acetylphenylmethylthio)-5-[4-(4-chloro-phenoxy)butyl]-4-(1-octenyl)-4-hydroxy-2-cyclopentenone Of the 2-substituted-2-cyclopentenones of the above formula (I), 2-substituted-2-cyclopentenones represented by the following formula (I-b-11):

~ - 25 - 13356~9 OH
Rl_s ~ R2 - (I-b-11) ()n R34 wherein Rl, R2 and R34 are as defined above, but preferably R2 and R34 are aliphatic hydrocarbon groups having 1 to 10 carbon atoms which also have as the substitutent -COOR5 (where R5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or one equivalent cation); _oR6 (where R6 is a hydrogen atom;
an acyl group having 2 to 7 carbon atoms; a tri(Cl - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with a oxygen atom to which R6 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, an hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; and n represents 0, 1 or 2; can be prepared by subjecting 2-cyclopentenones represented by ~ 133~6~
the following formula (III-a):

O OH

~ 21 .. (III-a) wherein R2l and R3l represent an aliphatic hydrocarbon l~ group having l to l0 carbon atoms which may have as the substituent -CooR5l (where R5l is an alkyl group having l to l0 carbon atoms); -OR6l (where R6l is an acyl group having 2 to 7 carbon atoms; a tri(Cl - C7)hydro-carbonsilyl group; a group which forms an acetal bond together with an oxygen atom to which R6l is bonded; an aromatic hydrocarbon group also may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having l to 4 carbon atoms, and an alkoxy group having l to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(Cl - C7)-hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having l to 4 carbon atoms, and an alkoxy group having l to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having l to 4 carbon atoms and an alkoxy group having l to 4 carbon atoms; to epoxydization reaction to obtain 2,3-epoxycyclopenta-nones of the following formula (IV-a-l):

~ - 27 - 1335~9 O OH

\ .... (IV-a-1) wherein R 1 and R31 are as defined above, then reacting thiols represented by`-the following formula (V):
R -SH .... (V) wherein Rl represents a substituted or non-substituted hydrocarbon group having 1 to 10 carbon atoms with said 2,3-epoxycyclopentanones in the presence o~ a basic compound, a alumina or silica gel, and subsequently, subjecting the reaction product, if necessary, to oxidation reaction, deprotection reaction or protection reaction.
The starting material represented by the above formula (III-a) is known per se, and can be prepared by the method disclosed in Japanese Unexamined Patent Publication (Kokai) No. 59-164747.
In the above ~ormula (III-a), R21 and R31 represent an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -CooR51 (where R51 is an alkyl group having 1 to 10 carbon atoms);
-OR61 (where R61 represents an acyl group having 2 to 7 carbon atoms, a tri(C1 - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the hydrogen atom to which R61 is bonded; an aromatic hydrocarbon group which also may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxy-carbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a ~ - 28 - 133~669 tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms; an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a tri(Cl - C7~hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms an alkoxycarbonyl group lQ having 2 to S carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms. ~s specific examples of R and R3 , the same specific examples as described above for R2 and R3 in the above formula (I), respectively, can be included.
In the process of the present invention, the compounds of the above formula (III-a~ are subjected to epoxydization reaction. As the reagent for the epoxydization reaction, an alkylhydroperoxide such as t-butylhydroperoxide or hydrogen peroxide may be used, but preferably hydrogen peroxide is used. Although anhydrous hydrogen peroxide may be used, a 90 to 5%
aqueous hydrogen carbon, preferably 50 to 10% aqueous hydrogen peroxide is generally used. The amount of hydrogen peroxide used may be 1 to 50 equivalents, preerably 3 to 20 equivalents, relative to 2-cyclo-pentenones represented by the above formula (III-a).
Preferably the epoxydization reaction is carried out in the presence of a basic compound, and examples of such basic compounds include quaternary ammonium hydroxides such as tetramethyl ammonium hydroxide, and benzyltrimethyl ammonium hydroxide; hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; and carbonates such as sodium carbonate and potassium carbonate. Preferably, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal carbonates such as sodium carbonates and potassium carbonate particularly - 29 - 133 5~ 69 preferably sodium hydroxide, are used. The amount of the basic compound used may be 0.01 to 5 equivalents, preferably 0.05 to 2 equivalents, relative to the 2-cyclopentenones represented by the above formula (III-a).
The reaction solvent may include alcohols such as methanol, ethanol, and t-butyl alcohol;
ketones such as acetone and methyl ethyl ketone;
ethers such as dioxane, and dimethoxyethane, which 1~ are inert to hydrogen peroxide, and can be mixed with water, preferably alcohols such as methanol, ethanol, and t-butyl alcohol, particularly preferably methanol or ethanol.
The reaction temperature of the epoxydization reaction is preferably within -20 to 50C, more preferably -5 to 30C.
The reaction time of the epoxydization reaction may differ depending on the starting compound, the reagent, the reaction solvent is and the reaction temperature employed, but preferably is within 5 minutes to 5 hours, more preferably 10 minutes to 1 hour.
After completion of the epoxydization reaction, the 2,3-epoxycyclopentanones represented by the above formula (IV-a-l) can be isolated and purified by a conventional means such as extraction, washing, drying, concentration, and chromatography, but the unpuri~ied reaction mixture also ca~ be provided as such for the subsequent reactions without isolation of said 2,3-epoxycyclopentanones.
The 2,3-epoxycyclopentanones represented by the above formula (IV-a-l) obtained in the above epoxy-dization reaction are novel compounds. The reaction between the compounds of the above for (IV-a-1) and the thiols represented by the above formula (V) is carried out in the presence of a basic compound, alumina or silica gel.

13356&9 In the above formula (V), R represents a substi-tuted or non-substituted hydrocarbon having 1 to 10 carbon atoms. Specific examples of R include those which are the same as the specific examples described for the above formula (I).
When a basic compound is used in carrying out the reaction between the 2,3-epoxycyclopentenones of the above formula (IV-a-1) and the thiols of the formula (V), such basic compounds are preferably alkali metal hydroxides or carbonates such as sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate; or tertiary amines such as trimethylamine, triethylamine, and pyridine; bicyclo strong bases such as diazabicyclo[2.2.2]octane and diazabicyclo[3.4.0]-nonen; and quaternary ammonium salts such as benzyltrimethyl ammonium hydroxide. Particularly preferably, the above tertiary amines such as triethylamine are used.
To allow a better reaction, preferably an inert solvent is used. As the solvent to be used, any inert solvent which can dissolve the starting compound may be used, but preferably alcohols such as methanol and ethanol; ethers such as ethyl ether and tetrahydrofuran;
and hydrocarbons such as hexane and benzene, are used.
The amount of the solvent used should permit the reaction to proceed smoothly, and is preferably 1 to 100-fold volume of the starting material, more preferably 2 to 20-fold volume.
The amount of the thiols (V) to be used in the present invention is preferably stoichiometrically equimolar to the starting material (IV-a-1). The basic compound which catalyzes the reaction is preferably used in an amount of 0.001 to 20-fold mol, more preferably 0.1 to 2-fold mol, relative to the starting material (IV-a-1).
Preferably, the reaction temperature is within -20 to 100C, more preferably 0 to 30C, and preferably the ~ - 31 - 13356~

reaction time for completion of the reaction is 20 minutes to 2 hours.
After the reaction, the 2-substituted-2-cyclo-pentenones represented by the following formula (I-b-10):
O OH

Rl-s R21 .... (I-b-10) \R3'1 wherein R1, R21 and R31 are as defined above can be isolated and purified by treating the reaction mixture by a customary procedure. For example, isolation and purification can be performed by extraction, washing, concentration, and chromatography, or combinations thereof, but the unpurified reaction mixture can be subjected as such to oxidation reaction, deprotection reaction and/or protection reaction without isolation of said 2-substituted-2-cyclopentenones, to produce the compounds of the above formula (I-b-ll).
Preferably, such an oxidation reaction is carried out in an inert solvent in the presence of an oxidizing agent.
Examples of the oxidizing agent used when producing sulfoxide preferably include peracids such as hydrogen peroxide, peracetic acid, perbenzoic acid, and m-chloro-perbenzoic acid; and sodium metaperiodate, selenium dioxide, chromic acid, iodosylbenzene, hypochlorous 3~ acid, and t-butyl hydroperoxide; and when producing sulfone, preferably include hydrogen peroxide, hydrogen peroxide and a tungsten oxide or vanadium oxide catalyst, peracetic acid, perbenzoic acid, m-chloroperbenzoic acid, ruthenium oxide, and osmium tetraoxide.
As the inert organic solvent, for example, preferably acetic acid, methylene chloride, chloroform, - 32 - - 13356~9 ~ dicycloroethzne, benzene, and ethyl acetate are used.
Preferably the reaction temperature is within -78C
to 50C, more preferably -20C to 30C.
The reaction time may dif~er depending on the starting compound, the reaction temperature, and the kind of oxidizing agent, but preferably is 30 minutes to 38 hours.
For example, when a sulfoxide is to be produced by using an oxidizing agent which can produce both sulfoxide and sulfone, preferably the amount of the oxidizing agent is not enough to produce sulfone, for example, an amount of about 1 to about 1.5 e~uivalents relative to the (I-b-10) used, and the reaction is monitored by thin layer chromatography (i.e., TLC).
After completion of the reaction, the desired compound can be isolated and purified by conventional methods such as extraction, washing, concentration, and chromatography.
Further, a desired compound having protective groups in the molecule can be subjected to deprotection reaction.
Elimination of the protective group, when the protective group is a group forming an acetal bond together with oxygen atom of hydroxyl group, is preferably carried out by using acetic acid, and a pyridinium salt of p-toluenesulfonic acid or cation ion exchange resin as the catalyst, and by using a reaction solvent such as water, tetrahydrofuran, ethyl ether, 3~ dioxane, acetone, and acetonitrile. Preferably the reaction is carried out at a temperature of from -78C
to +30~C, for about 10 minutes to 3 days. When the protective group is a tri(C1 - C7)hydrocarbonsilyl group, the reaction may be practiced in the reaction solvent as mentioned above in the presence of, for example, acetic acid, hydrogen fluoride-pyridine, tetrabutylammonium fluoride, and cesium fluoride at the - 33 - 13 3 S~ ~9 same temperature and for the same time. When the protective group is an acyl group, the reaction may be practiced by carrying out hydrolysis in, for example, an aqueous solution of sodium hydroxide, potassium hydroxyde, and calcium hydroxide, or a water-alcohol mixture or a methanol or ethanol solution contA i n ing sodium methoxide, potassium methoxide, and sodium ethoxide.
An ester group in the required compound can be subjected to hydrolysis, which can be carried out by using an enzyme such as lipase in water or a solvent containing water at a temperature of from -10C to +60C for about 10 minutes to 24 hours.
When the desired compound has a carboxyl group in the molecule, the compound can be further subjected to a salt forming reaction, to obtain a corresponding carboxylic acid salt. The salt forming reaction is known per se, and may be practiced by carrying out the neutralization reaction with a basic compound such as sodium hydroxide, potassium hydroxyde, sodium carbonate, or ammonia, trimethylamine, monoethanolamine, and morpholine, by a customary procedure, in an amount substantially equal to the carboxylic acid.
Further, a desired compound having a hydroxyl group in the molecule can be subjected to protection reaction.
Known methods can be employed for the protection reaction of the hydroxyl group. For example, when the protective group is an acyl group such as an acetyl group, propionyl group, or benzoyl group, the protective group can be easily introduced by reacting an acid halide or an acid anhydride with pyridine. When the protective group is a trihydrocarbonsilyl group such as a trimethylsilyl group or t-butyldimethylsilyl group, the protective group can be introduced by reacting a trihydrocarbonsilyl halide in the pressure of amines such as triethylamine and dimethylaminopyridine. When the protective group is a tetrahydropyran-2-yl group, - 3~ _ 1335669 tetrahydrofuran-2-yl group, or 1-ethoxyethvl group, the protective group can ~e introduc~d by placing the compound in contact with dihydropyrane, dihydrofuran, or ethyl vinyl ether, which is a correspondir~g vinyl other compound, in the presence of an acidic catalyst such as p-toluenesulfonic acid, and thus novel 2-substituted_2_ cyclopentenones represented by the above formula (I-b-11) are prepared.
When alumina or silica gel is used during the rezction between the 2,3-epoxycyclopentenones of the a~ove formula (IV-a-1) and the thiols of the formula (V), s~ch alumina or silica gel may be silica gel or alumina used generally during a sepzration and purification of an organic compound. For the silica gel, for example, *Wakol Gel C-300, *Wakol Gel 200 (pro-duced by Wako Pure Chemical Industries, Ltd.) may be emp-loyed. Similarly, for the alumina, for example, prefer-ably basic alumina (basic alumina produced by Woelm Co.), acidic alumina (neutral alumina produced by Woelm Co.), and active alumina are used, more preferably, basic alumina.
To allow a better reaction, preferably an inert solvent is used. As the solvent, any inert solvent which can dissolve the starting compound may be used, but preferably alcohols such as methanol and ethanol, ethers such as ethyl ether and tetrahydrofuran, and hydrocarbons such as hexane and ben~ene are employed.
The amount of the solvent should permit the reaction to proceed smoothly, but pre~erably 1 to 100-fold volumes of the starting material, more preferably 2 to 20-fold volumes are employed.
The amount of the thiols (V) to be used in the present invention is preferably stoichiometrically equimolar to the starting material (IV-a-1). The silica gel and alumina which catalyse the reaction is preferably used in an amount of 0.1 to 20-fold weight, more preferably 0.5 to 5-fold weight, relative to the starting material (IV-a-1).

*Trade mark 13356~9 Preferably, the reaction temperature is within -20 to 100C, more preferably 0 to 30C. The reaction time may differ depending on the catalyst amount and the solvent used, but preferably the reaction is completed within 10 minutes to 24 hours.
After the reaction, the 2-substituted-2-cyclo-pentenones represented by the above formula (I-b-10) can be obtained only by filtering the reaction mixture to remove alumina and silica gel, and evaporating the reaction solvent, but for a further purification, they also can be obtained by the methods of, for example, recrystallization and chromatography, or a combination thereof.
Of the 2-substituted-2-cyclopentenones of the above formula (I), the 2-substituted-2-cyclopentenones represented by the following formula (I-a-l).

Rl-lS~ R .... (I-a-l) ()n R34 ~, wherein R , R , R3 and n are as defined above; the representation .~ ~ denotes that the substituent bonded to the double bond is in an E-configuration or a Z-configuration or mixtures thereof at any desired ratio; can be produced according to the present invention by dehydrating the 2-substituted-2-cyclopentenones represented by the following formula (I-b-lO):
O OH
R1-s ~ / \ R21 .... (I-b-10) - 36 - ~33~9 wherein R1, R21 and R31 are as defined above, and subjecting the dehydrated product to oxidation, deprotection reaction and/or protection reaction.
In the above formula tI-b-10), R represents a substituted or non-substituted hydrocarbon group having 1 to 10 carbon atoms. Specific examples of Rl include the same specific examples as described above for the formula (I).
In the above formula (I-b-10), R 1 and R31 represent an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -CooR5 (where R51 is an alkyl group having 1 to 10 carbon atoms) or _oR6 (where R6 is an acyl group having 2 to 7 carbon atoms; a tri(C1 - C7)hydrocarbonsilyl group, a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom~ a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms. In the above formula (I-b-10), specific examples of R21 and R31 include the same specific examples as 133~669 described for R2 and R3 in the above formula (I).
In the process, the compounds of the aDove formula (I-b-10) are subjected to dehydration reaction. Dehydration reaction is preferably carried out by using a basic compound and a reactive derivative of an organic sulfuric acid. ~ore specifically, the compound of the above formula (I-b-10) is preferably first treated with a basic compound and a reactive derivative of an organic sulfonic acid, and further treated with a basic compound. The dehydration reaction is completed by a sulfonylation of the hydroxyl group of the compound of the formula (I-b-ll), and then elimination of an organic sulfonic acid.
Preferably, amines are used as the basic compound together with the deri~ative of an organic sulfonic acid, and examples of such amines include pyridine, 4-dimethylaminopyridine, triethylamine, diisopropyl-cyclohexylamine, 1,5-diazabicyclo[4.3.0]non-5-ene (hereinafter abbreviated as DBN), 1,8-diazabicyclo-~5.4.0]undec-7-ene (hereinafter abbreviated as DBU), quinacridine, triethylenediamine, isopropyldimethyl-amine, and diisopropylethylamine. Particularly, preferably are pyridine, 4-dimethylaminopyridine, DBU, and DBN.
Examples of reactive derivatives of organic sulfonic acid include organic sulfonic acid halides such as methanesulfonylchloride, ethanesulfonylchloride, n-butanesulfonylchloride, t-butanesulfonylchloride, trifluoromethanesulfonylchloride, benzenesulfonyl-chloride, and p-toluenesulfonylchloride; and anhydrous organic sulfonic acids such as anhydrous methanesulfonic acid, anhydrous ethanesulfonic acid, anhydrous trifluoromethanesulfonic acid, anhydrous benzenesulfonic acid, and anhydrous p-toluenesulfonic acid.
The basic compound itself as mentioned above may be also used as the solvent, but prefera~ y halogenated hydrocarbons such as dichloromethane, chloroform, carbon - 38 - 1335~9 tetrachloride, and dichloroethane; ethers such as ether and tetrahydrofuran; and hydrocarbons such as benzene, toluene, pentane, hexane, and cyclohexane are used. Most preferably, pyridine and dichloromethane is used.
Preferably, the derivative of an organic sulfonic acid is used at a ratio of 1 to 10 equivalents relative to 1 mol of the compound of the above formula (I-b-10).
Preferably, the basic compound is used at a ratio of 1 equivalent or more, most preferably 2 or more equivalents, relative to the reactive derivatives of the organic sulfonic acid employed.
Preferably, the amount of the solvent used is 1 to 1000-fold volume, more preferably 5 to 100-fold volume, relative to the compound represented by the above formula (I-b-10). The reaction temperature may differ depending on the starting compound, the basic compound, and the solvent, etc. employed, but preferably is from -40C to 100C, more preferably from 0C to 30C. The reaction time depends on the conditions, but preferably is about 0.1 to 10 hours. The progress of the reaction is monitored by a method such as thin layer chromato-graphy.
Therefore, according to the above reaction (hereinafter referred to as the first reaction), an organic sulfonyloxyoxy derivative is formed in which the hydroxyl group on the alkyl group at the 5-position of the 2-substituted-2-cyclopentenones of the above formula (I-b-10) is converted to an organic sulfonyloxy group, and the compound is subsequently treated with a basic compound (hereinafter referred to as the second reaction) to eliminate a corresponding organic sulfonic acid, thereby giving 2-substituted-2-cyclopentenones represented by the following formula (I-a-10):

o 133~669 ~l_S ~ ~21 --- (I-a-10) wherein R , R R and the representation ^ -^ are as defined above.
As the basic compound which can be used in the 1~ second reaction, the same basic compounds as mentioned in the above first reaction may be included, or the basic compound used in the second reaction may be different from that used in the first reaction.
The second reaction can be permitted to proceed within the same temperature range. Also, the organic sulfonyloxy derivative may be isolated and then subjected to the second reaction, or the first reaction and the second reaction may be carried out in the same reaction system. After completion of the reaction, the desired compound can be isolated and purified by conventional means such as extraction, washing, concentra~ion, chromatography or combinations thereof, but if necessary, the unpurified reaction mixture can be subjected as such to oxidation, deprotection reaction and/or protection reaction without isolation of said 2-substituted-2-cyclopentenones, whereby 2-substituted-2-cyclopentenones of the above formula (I-a-1) can be prepared. Such oxidation reaction, deprotection reaction or protection reaction can be accomplished by the same methods as used for producing the 2-substi-tuted-2-cyclopentenones represented by the above formula (I-b-11) from the 2-substituted-2-cyclopentenones represented by the above formula (I-b-10).
Of the 2-substituted-2-cyciopentenones of the above formula (I), the 2-substituted-2-cyclopentenones represen-ted by the above formula (I-a-1) and the 2-substituted-2-cyclopentenones ~ 40 - 13356~9 represented by the following formula (I-b-12):
( ~1 ) m O S-R

Rl-s ~\~/~ \ R2 ~ (I-b-12) (o)n~ - R34 1 n wherein R1, R2, R34 and n are as defined above and m is O, 1 or 2 can be produced by allowing 2,3-epoxy-cyclopentanones represented by the following formula (IV-a-2):

~ R 1 / \ / --. (IV-a-2) wherein R21, R31 and the representation ~,v~~ are as deined above to react with thiols represented by the following formula (V):
R -SH . .... (V) wherein Rl is the same as defined above in the presence of a basic compound, alumina or silica gel, and then carrying out an oxidation reaction, deprotection reaction and/or protection reaction, if desired.
The starting material represented by the above formula (IV-a-2) is a material known per se, and can be prepared by, for example, the method described in Japanese Unexamined Patent Publication (Kokai) No. 61-47437.
In the above formula (IV-a-2), R and R31 represent an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -CooR5 (where R51 is an alkyl group having 1 to 10 carbon atoms); -OR61 (where R51 is an acyl group having 2 to 7 ~ - 133566~
carbon atoms; a tri(Cl - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic hydrocarbon group which may be substituted with a halosen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an al~yl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 - 15 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, a acyl group having 2 to 7 carbon atoms, an al~oxycarbonyl group ha~ing 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms. In the above formula (IV-a-2), specific examples of R21 and R31 include the same specific examples as mentioned above for R2 and R3 in the above formula (I).
In the above formula (V), R1 represents a substi-tuted or non-substituted hydrocarbon group having 1 to 10 carbon atoms, specific examples of R1 may include the same specific examples as mentioned above for the above formula (I).

The reaction is carried out between 2,3-epoxycyclopenta-nones represented by the above formula (IV-a-2) and the thiols represented by the above formula (V) in the presencç of a basic compound, alumina or silica gel, and then the reaction product is subjected to oxidation reaction, deprotection reaction and/or protection - 42 - ~I335669 reaction, i~ desired, whereby the 2-substituted-2-cyclopentenones represented by the above formula (I-a-1) and (I-b-1~) can be obtained. Such production processes can be accomplished by the same processes for producing 2-substituted-2-cyclopentenones represented by the above formula (I-b-11) from the 2,3-epoxycyclopentenones represented by the above formula (IV-a-1) and the thiols represented by the above formula (V).
Of the 2-substituted-2-cyclopentenones of the above formula (I), the 2-substituted-2-cyclopentenones represen~ed by the following formula (I-b-2):

O OH

_s ~ ' ~ \ R2 ... (I-b-~) ()n ~ R34 \
OR-wherein R1, R2, R34 and n are as defined above; and R
represents a hydrogen atom or a protected group of the protected hydroxyl group; can be prepared by subjecting the 2-substituted-2-cyclopentanones represented by the following formula (III-b):
o Il ~ ,... (III-b) \\R31 o~4o wherein R31 represents an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may be as ~he substituent -CooR51 (where R51 is an alkyl group having 1 to 10 carbon atoms); -OR51 (where R61 is an acyl group having 2 to 7 carbon atoms; a tri(C1 ~ 43 ~ 133~669 - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to ?
carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; and R40 represents a hydrogen atom or a protected group of the protected hydroxyl group to epoxydization reaction to obtain the 2,3-epoxycyclopentanones represented by the followlng formula (IV-b-1):
O

0 ~ R3~ - (IV-b--l) oR4 o wherein R31 and R40 are the same as defined above, which can be subjected to deprotection of R31, if desired, to result in R34, then reacting the 2,3-epoxycyclopentanones with the thiols represented by the following formula (V):

133~6~9 R1_SH ... (V) wherein R1 is as defined above, further protecting the hydroxyl group, if desired, to obtain the 2-substituted-2-cyclopentenones represented by the following formula (I-c-l):
o Rl_5 ~ ....................... (I-c-l) oR40 wherein R1, R34, and R40 are the same as defined above; and for the further reaction, converting R34 to R31 and R40 to R41 which represents a protective group of the protected hydroxyl group, subjecting this to aldol condensation reaction with aldehydes represented by the following formula (II):

OHC-R21 (II) where R21 is as defined above, and subsequently subjecting the reaction product to oxidation reaction, deprotection reaction and/or protection reaction, if desired.
The starting material represented by the above formula (III-b) is a material known E~ se, and may be prepared by the method described in Japanese Unexamined Patent Publication (Kokai) No.
62-96438. In the above formula (III-b), R31 represents an aliphatic hydrocarbon group having l to lO carbon atoms which may have as the substituent -CooR51 (where R51 is an alkyl group having l to lO carbon atoms); -oR61 (where R61 is an acyl group having 2 to 7 carbon atoms); a tri (Cl-C7) hydrocarbonsilyl group;
a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, an acyloxy group having 2 to 7 carbon ~ 45 ~ 1~ 356 69 atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having l to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.
Specific examples of R31 include the same specific examples as mentioned above for R3 in the above formula (I). In the above formula (III-b), R4 represents a hydrogen atom or a protected group of the protected hydroxyl group. Specific examples of R40 include a hydrogen atom; alkyl groups such as methyl, ethyl, propyl, and isopropyl; tri(Cl - C7)hydrocarbon-silyl groups such as trimethylsilyl, triethylsilyl,t-butyldimethylsilyl, t-butyldiphenylsilyl, and tribenzylsilyl; groups which form an acetal bond together with the oxygen atom to which R40 is bonded such as methoxymethyl, l-ethoxyethyl, 2-methoxyethoxymethyl, and tetrahydropyran-2-yl; and acyl groups such as acetyl, propionvl and butvrvl.

The compound of the above formula (III-b) is subjected to epoxydization reaction to obtain the 2,3-epoxycyclo-pentanones of the above formula (IV-b-l). The epoxy-dization reaction method can be the same method used for preparation of the 2,3-epoxycyclopen~anones represented - ~6 -by the above formula (IV-a-1) by subjecting the 2-cyclopentenones represented by the above formula tIII-a) to epoxydization reaction.
The 2,3-epoxycyclopentanones represented by the above formula (IV-b-l) obtained in the above epoxy-dization rezction are novel compounds. The reaction between the compounds of the above formula (IV-b-l) and the thiols represented by the above formula (V) is carried out in the presence of a basic compound, alumina or silica gel.
In the above formula (V), Rl represents a substi-tuted or non-substituted hydrocarbon group having 1 to 10 carbon atoms. Specific examples of R1 include the same specific examples as mentioned above for the above formula (I).

The reaction is carried out between the 2,3-epoxycyclo-pentanones represented by the above formula (IV-b-l) and the thiols represented by the above formula (V) in the presence of a basic compound, alumina or silica gel, and then the reaction product is subjected to protection reaction to obtain the 2-substituted-2-cyclopentenones represented by the above formula (I-c-1); if desired.
This production process can be accomplished by the same process used for producing the 2-substituted-2-cyclo-pentenones represented by the above formula (I-b-10) from the 2,3-epoxycyclopentanones represented by the above formula (IV-a-l) and the thiols represented by the above formula (v).
The 2-substituted-2-cyclopentenones represented by the above formula (I-c-l) obtained in the above reaction are novel compounds. In the above formula tI-c-1), R represents a protected group o~ the protected hydroxyl group. Specific examples of R41 include al~yl groups such as methyl, ethyl, propyl, and - isopropyl; tri(C1 - C7)hydrocarbonsilyl groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, - ~7 ~ 13356~9 t-butyldiphenylsilyl, and tribenzylsilyl; groups which form an acetal bond together with the oxygen atom to which R41 is bonded such as methox~methyl, 1-ethoxyethyl, 2-methoxyethGxymethyl, and tetrahydropyran-2-yl; and acyl groups such as acetyl, propionyl, and butyryl.

The compounds represented by the above formula (I-c-1) and the aldehydes represented by the above formula (II) are subjected to aldol condensation reaction.
In the above formula (II), R21 represents an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -CooR51 (where R51 is - an alkyl group having 1 to 10 carbon atoms); -OR61 (where R~1 is an acyl group having 2 to 7 carbon atoms;
a tri(C1 - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7.carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group havlng 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.

~ - 48 - 1335669 Specific examples of R include the same specific examples as mentioned above for R2 in the above formula (I).

The compounds represented by the above formula (I-c-l) and the aldehydes represented by the above formula (II) are subjected to aldol condensation reaction.
The aldol condensation reaction is carried out in the presence of a basic compound in a solvent.
Examples of the basic compound and the reaction solvent include those described in: A. T. Nielsen, W. J.
~aulihan, Organic Reaction (Org. React.), 16, 1 (1968);
~. O. House, "Modern Synthetic Reactions" 2nd Ed., Benjamin (1972), p. 629; and New Experimental Chemistry Course 14, II736, III851, etc.
For the aldol condensation reaction, preferably metal amides such as lithium diisopropylamide, lithium diethylamide, and lithium bistrimethylsilylamide; or dial~ylborontrifluoromethanesulfonic acids such as dibutylborontrifluoromethanesulfonic acid in the presence of a tertiary amine such as triethylamine, diisopropylethylamine, and tributylamine, are employed.
When the aldol condensation reaction is carried out by using a metal amlde, preferably the amount thereof is 0.2 to 50 equivalents, more preferably 0.9 to 10 equivalents, relative to the compound of the above formula (I-c-l). As the reaction solvent, or example, ethers such as ether and tetrahydrofuran; and hydro-carbons such as petroleum ether, hexane, and pentane, may be employed. Preferably the reaction temperature is from -150C to 100C, more preferably from -80~C to 0C.
When the aldol condensation reaction is carried out by using a tertiary amine and a dialkylboryl trifluoro-methanesulfonate, preferably the amounts used thereof are, for example, 0.5 to 50 equivalents, more preferably 1 to 10 equivalents, relative to the compound of the above formula (I-c-1).

~ 49 ~ 13356~
The aldehyde of the formula (II), which is the other starting material, preferably is used at a ratio of 0.S to 10 equivalents, more prefexably 0.8 to 2 equivalents, relative to the compound of the formula (I-c-1).
The reaction time depends on the starting compound, the reagents, and the reaction solvent employed, but preferably is from 5 minutes to 48 hours, more preferably from 10 minutes to 12 hours.
After completion o~ the reaction, the 2-substi-tuted-2-cyclopentenones represented by the following formula (I-b-20):
O OH

R1_5 _ R --- (I-b-20) oR41 h ei R1 R21 R31 and R~l are as defined above can be obtained by isolating and purifying the reaction mixture by a conventional means such as extraction t water washing, drying, a~d chromatography, but the unpurified reaction mixture can be subjected to an oxidation reaction, deprotection reaction or protection reaction without isolation of said 2-substituted-2-cyclopentenones, whereby the compound of the abovP
formula (I-b-2) can be prepared. Such an oxidation reaction, deprotection reaction or protection reaction can be carried out by the same methods as used in the preparation of the 2-substituted-2-cyclopentenones represented by the above formula (I-b-ll) from the 2-substituted-2-cyclopentenones represented by the.above 3S formula (I-b-10).
Of the 2-substituted-2-cyclopentenones of the above formula (I), the 2-substituted-133~669 2-cyclopentenones represented by the following formula (I-a-2):
O

R~ O ~ R2 .... (I-a-2) ()n ~ R34 OR

wherein R , R R34, R4, n and the representation ~___ are as defined above can be prepared by dehydrating the 2-substituted-2-cyclopentenones represented by the following formula (I-b-20):
O OH

R1 S ~ R21 --- (I-b-20) oR41 wherein R1 R21 R31 and R41 are as defined above and subsequently subjecting the dehydrated product to an oxidation reaction, deprotection reaction and/or protection reaction, if désired.
In the above formula (I-b-20), R1 represents a substituted or non-substituted hydrocarbon group having 1 to 10 carbon atoms, and specific examples of Rl include the same specific examples as mentioned above for the above formula (I).
In the above formula (I-b-20), R21 and R
represent an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -CooR5 (where R51 is an alkyl group having 1 to 10 carbon atoms) or -OR61 (where R61 is an acyl group having 2 to 7 carbon atoms; a tri(C1 - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic ~ - 51 - 13356~9 hydrocarbon group which may be substituted wi~h a halosen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, ~n acyl group having 2 to 7 carbon atoms, an alkoxycar~onyl grour having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms; and an alkoxy grou?
having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 c2rbon atoms, and an alkoxy group having 1 to 4 carbon atoms;
or an alicyclic group which may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having l to 4 carbon atoms. Specific examples of R21 and R31 in the above formula (I-b-20) include the same specific examples as mentioned above or R2 and R3, respectively for the above formula (I).
In the above formula (I-b-20), R41 represents a protected group of the protected hydroxyl group.
Specific examples of R41 include alkyl groups such as methyl, ethyl, propyl, and isopropyl; tri(C1 - C7)-hydrocarbonsilyl groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiDhenyl-silyl, and tribenzylsilyl; groups which form an acetalbond together with the oxygen atom to which R41 is bonded such as methoxymethyl, l-ethoxyethyl, 2-methoxyethoxymethyl, and tetrahydropyran-2-yl; and acyl groups such as acetyl, propionyl, and bu~yryl.
The compound of the above formula (I-b-20) is subjected to dehydration reaction. This dehydration reactlon can be - 52 - 133566~

carried out by the same method as used in the prepa-ration of the 2-substituted-2-cyclopentenones represented by the above formula (I-b-10) from the 2-substituted-2-cyclopentenones represented by the above formula (I-b-10), whereby 2-substituted-2-cyclopente-nones represented by the following formula (I-a-20):
o .... (I-a-20) OR

i Rl R21 R31 R41 and the representation ~~~--are as defined above can be obtained.
The compound o~ the above formula (I-a-20) can be further subjected to oxidation reaction, deprotection reaction or protection reaction, if desired, to be converted to 2-substituted-2-cyclopentenones of the above formula (I-a-2). This oxidation reaction, deprotection reaction andJor protection reaction can be carried out by the same method as used in the prepa-ration of the 2-substituted-2-cyclopentenones represented by the above formula (I-b-ll) from the 2-substituted-2-cyclopentenones represented by the above formula (I-b-10).

Of the 2-substituted-2-cyclopentenones of the above formula (I), the 2-substituted-2-cyclopentenones represented by the following formula (I-a-3'):

R -S - R33 --- (I-a-3~) 133~669 wherein R1, R , n and the representation ~~ are as defined above; and R33 represents a hydrogen atom or an aliphatic hydrocarbon group having 1 to 9 carbon atoms having as the substituent -CooR5 (where R5 represents hydrogen atom, an alkyl group having 1 to 10 carbon atoms or one equivalent cation); _oR6 (where R6 is an acyl group having 2 to 7 carbon atoms; a tri(Cl - C7)-hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R6 is 1~ bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a caroboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an al~oxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a hydroxyl group, a tri(Cl - C7)hydrocarbonsilyloxy group, a carboxyl ~group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; can be prepared by subjecting the 2-substituted-2-cyclopentenones represented by the formula (I-a-21):

, 133s669 Rl_s ~ ~R21 .... (I-a-21) ()n \ ~ R32 oR4 wherein R , R , R , n and the representation ~~~ are as defined above; and R represents a hydrogen atom or an aliphatic hydrocarbon group having 1 to 9 carbon atoms which may have as the substituent -CooR51 (where R51 is an alkyl group having 1 to 10 carbon atoms);
-OR61 (where R61 is an acyl group having 2 to 7 carbon atoms; a tri(C1 - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be 3~ substituted with a halogen atom, a tri(Cl - C7)-hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having l to 4 carbon atoms; and subsequently sub~ecting the reaction product to an oxidation reaction, deprotection reaction and/or 13356~9~

protection reaction, if desired.
. In the above formula (I-a-21), R1 is substituted or non-substituted hydrocarbon group having 1 to 10 carbon atoms, and specific examples of Rl include the same specific examples as mentioned above for the above formula (I).
In the above formula (I-a-21), R21 is an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -COOR51 (where R51 is an alkyl group having 1 to 10 carbon atoms); _oR6 (where R is an acyl group having 2 to 7 carbon atoms; a tri(Cl - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 29 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an aliphatic group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyloxy group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.
Specific examples of R21 include the same specific examples as mentioned for Rl in the above formula (I).
In the above formula (I-a-21), R32 represents a hydrogen atom or an aliphatic hydrocarbon group having 1 - ~6 - 1335669 to 9 carbon atoms which may have as the substituent -CooR51 (where R51 is an alkyl group having 1 to 10 carbon atoms); -OR61 (where R61 is an acyl group having 2 to 7 carbon atoms; a tri(C1 - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R6 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl groups having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms;
2~ or an alicyclic group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms. Specific examples of R32 include the same specific examples as mentioned for R33 in the above formula (I").
In the above formula (I-a-21), R4 represents a 3~ hydrogen atom, or a protected group of protected hydroxyl group. Specific examples of R4 include a hydrogen atom; alkyl groups such as methyl, ethyl, propyl, and isopropyl; tri(C1 - C7)hydrocarbonsilyl groups such as trimethylsilyl, triethylsilyl, t-butyl-dimethylsilyl, t-butyldiphenylsilyl, and tribenzylsilyl;
groups which form an acetal bond together with the protective group of the protected hydroxyl group such as ~ 57 ~ ~3~
-methoxyme~hyl, l-ethoxyethyl, 2-methoxyethoxymethyl, and tetrahydropyran-2-yl and acyl groups such as acetyl, propionyl, and butylyl.
The 2-substituted-2-cyclopentenones represented S by the above formula (I-a-21) can be prepared by forming an alkyldiene group at the 4-position of the cyclopentenone skeleton by an elimination reaction, carrying ou~ the oxidation reaction when S bonded at the 2-position is to be converted to sulfoxide or sulfone, and further, subjecting the reaction product to a deprotection reaction of a hydroxyl group or carboxyl group, and/or a protection reaction.
The compound of the above formula (I-a-21) ls subjected to an elimination reaction, which is preferably practiced by using an acidic compound. As the acidic compound, there may be employed organic carboxylic acids such as acetic acid, propanoic acid, butanoic acid, oxalic acid, malonic acid, tartaric acid, and ~en~oic acid; inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and hydrofluoric acid; organic sulfonic acids such as p-toluenesulfonic acid, methanesulfonic acid, and benzenesulfonic acid, but preferably, acetic acid is used.
The solvent to be used includes water; alcohols such as methanol and ethanol; ethers such as ether, tetrahydrofuran, dioxane, and dimethoxyethane; aprotic polar solvents such as hexamethylphosphoric triamide, 3~ dimethylformamide, and dimethylsulfoxide; halogenated hydrocarbons such as dichloromethane and chloroform; and acetonitrile and nitromethane, which may be used alone or as a mixture thereof.
The acidic compound may be be used at a ratio preferably of 0.001 to 1000 equivalents per 1 mol of the compound of the above formula (I-a-21).
Preferably, the amount of the solvent used is 1 to ~ - 58 - 1335 6 B9 1000-fold volume, more preferably 5 to 100-fold volume, relative to the compound represented by the above formula (I-a-21). The reaction temperature may differ depending on the starting compound, the acidic compound, and the amount of solvent employed, but preferably is rom -20C to 100C, more preferably from 0C to 50C.
The reaction time, which is differs depending on the conditlons, is about 0.1 to 100 hours. The progress of the reaction is monitored by a method such as chromatography.
After completion of the reaction, the desired compound may be puri~ied by a conventional means such as extraction, washing, concentration, and chromatography, or combination thereof, but the unpurified reaction mixture can be subjected as such, without isolation of the desired compound, to an oxidation reaction, deprotection reaction or protection reaction, i~
desired, to prepare the 2-substituted-2-cyclopentenones represented by the above formula (I-a-3). This oxidation reaction, deprotection reaction and/or protect7on reaction can be carried out by the same method as used in the preparation of the 2-substituted-2-cyclopentenones represented by the above formula (I-b-11) from the 2-substituted-2-cyclopentenones represented by the above formula (I-b-10).
Of the 2-substituted-2-cyclopentenones of the above formula (I), the 2-substituted-2-cyclopentenones represented by the following formula (I-a-3'):

R -S ~ R2 .... (I-2) ~) ~ 3 X

~ - 59 - 1335669 wherein R1, R2, R3 and ~ are as defined above;
A11 and B are such that A11 represents a hydroxyl group or ( ) i and B represents a hydrogen atom or A11 and B together represent a single bond k is 1 or 2; and i is 0, 1, or 2, can be prepared by subjecting the 2-substituted-2-cyclopentenones represented by the following formula (I-1):
B A

R -S ~ ~ R21 .... (I-1) (~ ~ --7\R30 wherein R1 and R~1 are as defined above; A12 and B are such that A12 represents a hydroxyl group or -S-R
and B represents a hydrogen atom or A12 and B
together represent a single bond; and R30 represents 25 . a substituted or non-substituted aliphatic hydrocarbon group having 1 to lO carbon atoms, when R30 is a single bond and is bonded to the cyclopentene s~eleton, X0 represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group, and when R30 is a double bond 3~ and bonded to the cyclopentene skeleton, X0 represents a bonding arm constituting a part of said double bond;
~ is 0 or 1; and j is O, 1, or 2; to oxidation reaction, and then to deprotection reaction and/or protection reaction, if desired.
In the above formula (I-1), A12 and B represent a combination in which B is a hydrogen atom when A12 is a hydroxyl group or ~ - 60 --S-R , or A12 and B are mutually bonded together to represent one bonding arm. Specific examples of Al and B include the same specific examples as mentioned above for the above formula (I).
In the above formula (I-l), R represents a substituted or non-substituted hydrocarbon group having 1 to 10 carbon atoms. Specific examples of R1 include the same specific examples as mentioned above for the above formula (I).
In the above formula (I-1), R21 represents an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -CooR51 (where R5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or one equivalent cation); -OR
(where R61 is an acyl group having 2 to 7 carbon atoms;
a tri(C1 - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 ~ - 61 - 13356~9 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.
Specific examples of R21 include the same specific examples as mentioned above for R2 in the above formula (I).
In the above formula (I-1), R30 represents a substituted or non-substituted aliphatic hydrocarbon group having 1 to lO carbon atoms. Where R30 is a single bond and bonded to the cyclopentene s~eleton, XO
l~ represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group, and when R30 is a double bond and bonded to the cyclopentene skeleton, X represents a bond in said double bond. Specific examples of R30 and XO include the same specific examples as mentioned above for R3 and X, respectively, in the above formula (I).
In the above formula (I-1), Q represents O or 1 and j represents 0, 1 or 2. In the process, the 2-substituted-2-cyclopentenones represented by the above by subjecting the compound of the above formula 2~ l) to an oxidation reaction, and further to a deprotection reaction and!or protection reaction, if necessary, formula (I-2) can be prepared.
This oxidation reaction, deprotection reaction and/or protection reaction can be carried out by the same method as used in the preparation of the 2-substituted-2-cyclopentenones represented by the above formula (I-b-11) from the 2-substituted-2-cyclopentenones represented by the above formula ~I-b-lO).
The preparation processes according to the embodi-ments as shown below are applicable.

l. A process for preparing the 2-substituted-2-cyclopentenones represented by the following formula (I-b-11):

~ - 62 -133~6~9 OH
Rl_S ~ R2 --- (I-b-ll) (O) R34 n wherein Rl is as defined above;
As defined above, R2.and R34 are preferably aliphatic hydrocarbon groups having 1 to 10 carbon atoms which may have as the substitutent -CooR5 (where R5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or one equivalent cation); _oR6 ( where R6 is a hydrogen atom; an acyl group having 2 to 7 carbon atoms; a tri(Cl - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with a oxygen atom to which R6 is bonded; an aromatic hydrocarbon group which may be also substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydro-carbon group which may be~substituted with a halogen atom, a hydroxyl group, a tri(Cl - C7)hydrocarbon-silyloxy group, a carboxyl group, an acyloxy grouphaving 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a hydroxyl group, a tri(Cl - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy - group having 1 to 4 carbon atoms; and n represents 0, 1 or 2, which ~ - 63 - 133S6~9 comprises subjecting the 2-cyclopentenones represented by the following formula (III-a~:
OH
/ \-~ \ R21 .... (III-a) wherein R21 and R31 represent an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -CooR51 (where R51 is an alkyl group having 1 to 10 carbon atoms); _oR6 (where R61 is an acyl group having 2 to 7 carbon atoms; a tri(Cl - C7)hydro-carbonsilyl group; a group which forms an acetal bond together with a hydrogen atom to which R61 is bonded; an aromatic hydrocarbon group may be also substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydro-carbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a tri(Cl - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; to an epoxydization reaction to obtain the 2,3-epoxycyclo-pentanones of the following formula (IV-a-l):

~ - 64 -1~356~9 O OH

R .... (IV-a-1) 0~

wherein R21 and R31 are as defined above, then reacting thiols represented by the following formula (V):
R -SH .... (V) wherein R1 represents a substituted or non-substituted hydrocarbon group having 1 to 10 carbon atoms with said 2,3-epoxycyclopentanones in the presence of a basic compound, alumina and/or silica gel, and subsequently subjecting the reaction product, if necessary, to an oxidation reaction, deprotection reaction and/or protection reaction.
2. A process for preparing the 2-substituted-2-cyclopentenones represented by the following formula (I-a-l):

R -S ~ ~ ~R2 ... (I-a-1) ()n R34 wherein R1, R2, R34, and n are as defined above; and the representation ~r~r~ denotes that the substituent bonded to the double bond is in an E-configuration or a ~-configuration or mixtures thereof at any desired ratio which comprises dehydrating the 2-substituted-2-cyclo-pentenones represented by the following formula (I-b-10):

- 65 - 1335 6 ~9 OH
~1_5 ~ R21 ( wherein R1 R21 and R31 are as defined above and subsequently subjecting the dehydrated product to oxidation reaction, deprotection reaction and/or protection reaction.
3. A process for preparing the 2-substituted-2-cyclopentenones represented by the following formula (I-a-l):
O

Rl_s ~ ~R2 ..,. (I-a-1) ()n R34 R1 R2 R34 n and the representa are as defined above, and the 2-substituted-2-cyclopentenones represented by the following formula (I-b-12):
()m O S-R

Rl_s ~ ~ R2 .... (I-b-12) ()n R34 wherein Rl, R2, R34, and n are as defined above, and m represents 0, 1 or 2. which comprises allowing the 2,3-epoxycyclopentanones represented by the following formula (IV-a-2):

~ -- 6D

o ~ ~R
--- (IV-a-2) R

wherein R21, R31 and the representation ~~-- are as defined above, to react with thiols represented by the following formula (V):
R -SH .... (V) wherein R1 is as defined above, in the presence of a basic compound, alumina and/or silica gel, and then carrying out an oxidation reaction, deprotection reaction and/or protection reaction, if desired.
4. A process for preparing the 2-substituted-2-cyclopentenones represented by the following formula (I-b-2):
O OH

1 S ~ R2 .... (I-b-2) ()n ~ R34 oR4 wherein R1, R2, R34 and n are as defined above; and R4 represents a hydrogen atom or a protected group of the protected hydroxyl group, which comprises subjecting the 2-substituted-2-cyclopentenones represented by the following formula (III-b):
o Jl~
~\ .... (III-b) oR40 ~ - 67 -13356~9 wherein R31 represents an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -CooR51 (where R51 is an alkyl group having 1 to 10 carbon atoms); -OR51 (where R6 is an acyl group having 2 to 7 carbon atoms; a tri(C1 - C7)hydro-carbonsilyl group; a group which forms an acetal bond together with the o~ygen atom to which R61 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 t.o 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, 2Q and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; and R40 represents a hydrogen atom or a protected group of the protected hydroxyl group, to an epoxydization reaction to obtain the 2,3-epoxycyclo-pentanones represented by the following formula(IV-b-1):

O ~ ~ R31 --- (IV-b-1 oR4 o wherein R31 and R are as defined above, then reacting the thiols represented by the following formula (V):
R -SH .... (V) wherein R1 is as defined above, with the 2,3-epoxycyclopentanones in the presence of a basic compound, alumina and/or silica gel, and further protecting the hydroxyl group, if desired, to obtain the 2-substituted-2-cyclopentenones represented by the following formula (~-c-1):
o R1-S ~ .... (I-c-l) \\ R31 ' o wherein Rl and R31 are as defined above; and R41 represents a protected group of the protected hydroxyl group, and carrying out an aldol condensation reaction which aldehydes represented by the following formula (II):
oHc-R2l .... (II) wherein R21 is as defined above, and subse~uently, subjecting the reaction product to an oxidation reaction, deprotection reaction and/or protection reaction, if desired.
5. A process for preparing the 2-substituted-2-cyclopentenones represented by the following formula (I-a-2):
o R1-S ~ ~1~R2 .... (I-a-2) ()n ~ R34 OR

- 69 - 133S6~9 wherein R , R , R , R , n and the representation are as defined above, which comprises dehydrating the 2-substituted-2-cyclopentenones represented by the following formula (I-b-20):
` OH

Rl_s ~ R21 .... (I-b-20 . OR 1 wherein R1 R21 R31 and R41 are as defined above and subsequently subjecting the dehydrated product to oxidation reaction, deprotection reaction and/or protection reaction, if desired.
6. A process for preparing the 2-substituted-2-cyclopentenones represented by the following formula (I-a-3'):
o Rl_5 ~R33 , . . ( I-a-3 ' ) wherein R1, R2, n and the representation ~ are as defined above; and R33 represents a hydrogen atom or an aliphatic hydrocarbon group having 1 to 9 carbon atoms having as the substituent -CooR5 (where R5 represents hydrogen atom, an alkyl group having 1 to 10 carbon atoms or one equivalent cation); _oR6 (where R6 is an acyl group having 2 to 7 carbon atoms; a tri(C1 - C7)-hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R6 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(Cl - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having l to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms); an aromatic hydrocarbon ~roup which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to ~ carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; which comprises subjecting the 2-substituted-2-cyclopentenones represented by the formula (I-a-21):
o R1-S ~ \ , ~ R21 .... (I-a-21) ()n ~ ~ '~ R32 oR4 1 R21 R4 n and the representa are as defined above; and R32 represents a hydrogen atom or an aliphatic hydrocarbon group having 1 to 9 carbon atoms which may have as the substituent -CooR5 (where R51 is an alkyl group having 1 to 10 carbon atoms);
-OR61 (where R61 is an acyl group having 2 to 7 carbon atoms; a tri(Cl - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R51 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a ~ - 71 - 13~56~9 tri(C1 - C7)hydrocarbonsilyloxy group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having l to 4 carbon atoms, and an alkoxy group haviny l to 4 carbon atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxy group, a tri(Cl - C7)-hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having l to 4 carbon atoms, and an alkoxy group having l to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydro-carbonsilyloxy group, a carboxyl group, an acyloxy grouphaving 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group havi.ng l to 4 carbon atoms and an alkoxy group having l to 4 carbon atoms, and subsequently subjecting the reaction product to oxidation reaction, deprotection reaction and/or protection reaction, if desired.
7. A process for preparing the 2-substituted-2-cyclopentenones represented by the following formula (I-2):
B A

Rl_s ~ ~ R2 .... (I-2) (o)k\~\R3 wherein Rl, R2, R3 and X are as defined above; Al1 and B
are such that All represents a hydroxyl group or ( li ) il -S-R

~ - 72 - 13356~9 and B represents a hydrogen atom or A and B together represent a single bond; k represents 1 to 2; and i represents 0, 1 or 2, which comprises subjecting the 2-substituted-2-cyclopentenones represented by the following formula (I~
B A
R1-S ~ R21 .... (I-1) ()~ --~\ R30 XO

wherein R1 and R21 are as defined above; A12 and B are such that A12 represents a hydroxyl group or -S-R
and B represents a hydrogen atom or A12 and B together represent a slngle bond, and R30 represents a substituted or non-substituted aliphatic hydrocarbon group having 1 to 10 carbon atoms, when R30 is a single bond and is-bonded to the cyclopentene skeleton, x represents a hydrogen atom, hydroxyl group or a protected hydroxyl group,~and when R30 is a double bond and bonded to the cyclopentene skeleton, XO represents a bonding arm constituting a part of said double bond;
represents O or 1; and j represents 0, 1, or 2, to an oxidation reaction, and then to a deprotection reaction and/or protection reaction, if desired.

8. A process for preparing 2-substituted-2-cyclo-pentenones according to the above items 1 or 4, wherein the epoxydization reaction is carried out by using hydrogen peroxide in the presence of an alkali metal hydroxide or carbonate.

9. A process for preparing 2-substituted-2-cyclo-pentenones according to the above items 1, 3, 4 or 8, wherein the basic-compound to be used in the reaction - 73 - 133~6 ~9 with the thiols represented by the above formula (v) is an alkali metal hydroxide or carbonate, or an amine.

10. A process for preparing 2-substituted-2-cyclo-pentenones according to the above items 4, 8 or 9, wherein the aldol condensation reaction is carried out in the presence of a basic compound and dibutylboron-trifluoremethanesulfonic acid.

11. A process for preparing 2-substituted-2-cyclo-pentenones according to the above items 4, 8 or 9, wherein the aldol condensation reaction is carried out in the presence of lithium diisopropylamide.

12. A process for preparing 2-substituted-2-cyclo-pentenones according to the above items 2 or 5, wherein the dehydration reaction of the above formula (I-b-10) or (I-b-20) is carried out by using a basic compound and a reactive derivative of an organic sulfonic acid.

13. A process for preparing 2-substituted-2-cyclo-pentenones according to the above items 1 to 12, wherein the oxidation reaction is carried out by using an organic peracid.

14. a process for preparing 2-substituted-2-cyclo-pentenones according to the above items 1 to 12, wherein the oxidation reaction is~carried out by using an organic periodic acid salt.
The compound according to the present invention can be administered by oral, subcutaneous, intramuscular, intravenous, intraarterial, and suppository adminis-tration, etc., methods.
Solid preparations or liquid preparations can be formed for oral administration, and include, for example, tablets, pills, powders, granules, solutions, suspensions or capsules. When preparing tablets by a conventional method, excipients such as lactose, starch, calcium carbonate, crystalline cellulose or silicic acid; binders such as carboxymethyl cellulose, methyl cellulose, calcium phosphate or polyvinyl pyrrolidone;
disintegrating agents such as sodium alginate, sodium hydrogen carbonate, sodium lauryl sulfate or stearic acid monoglyceride; humectants such as glycerine;
absorbers such as kaolinj and colloidal silica; and lubricants such as talc and granular boric acid may be employed.
Pills, powders or granules also can be prepared by conventional methods using the same additives as mentioned above.
Liquid preparations such as solutions and suspensions also can be prepared by conventional methods. As the carrier, for example, glycerol esters such as tricaprin, triacetin, iodated poppy seed oil fatty acid esters; water; alcohols such as ethanol; and oily bases such as fluid paraffin, coconut oil, soybean oil, sesame oil, and corn oil may be employed.
The powders, granules, liquid preparations as described above also can be enclosed within capsules of, for example, gelatin.
The pharmaceutically acceptable carrier in the present specification also includes other auxiliary agents, aromatic agents, stabilizers or preservatives conventionally used as optional components.
The preparation for parental administration may be a sterile aqueous or nonaqueous solution, suspension or emulsion. The nonaqueous solution or suspension may employ propylene glycol and polyethylene glycol, or a vegetable oil such as olive oil, an injectable organic ester such as ethyl oleate, and iodated poppy seed fatty acid esters as the carrier. The preparation also can contain auxiliary agents such as preservatives, humectants, emulsifiers, dispersing agents, and stabilizers. These solutions, suspensions and emulsions can be sterilized by a treatment such as filtration through bacteria-retaining filter, formulation with a sterilizer, or irradiation. It is also possible to prepare a sterile solid preparation, which is dissolved in sterile water or a sterile solvent for injection ~ 75 - 133~6~9 immediately before use.
The compounds of the present invention also can be used by forming inclusion compounds together with ~, ~
or ~-cyclodextrin or methylated cyclodextrin, and may be injectable preparations in the lipogenated form.
The effective dose of the compounds of the present invention depends on the age, sex, and condition of the patient, but generally may be administered at 102 to 105 ~g/Kg/day, preferably 5 x 102 to 104 ~g/Kg/day.
The 2-substituted-2-cyclopentenones of the present invention have a potent growth inhibitory effect against L1210 leukemia cells even at a low concentration, are useful as antitumor agents.
Furthermore, the present compounds have the activities of enhancing the alkali phosphatase activity of human osteoblast, and further, enhancing the calcium and phosphorus contents in osteoblast. Accordingly, the present compounds are also useful as a bone formation accelerator, and are effective for the therapy or prophylaxis of osteoporosis or osteomalacia.
Furthermore, the present compounds are expected to exhibit an antiviral activity or antibacterial activity and are very useful components as the pharmaceutical products.
EXAMPLES
The present and related inventions are described in detail below with reference to Examples.
Example 1 Synthesis of 2,3-e~oxy-5-(1-hydroxy-6-methoxy-carbonylhexyl~-4-(3-t-butyldimethylsilyloxy-1-octenyl)-cyclopentanone - 76 - 13356~9 O OH

\,/ \ / \ COOCH3 ~\/
os i .x O OH

osi ,.~

A solution of 3.30 g of.5-(1-hydroxy-6-methoxy-carbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone in methanol (25 ml) was cooled to 0C, and 48 ml of an aqueous 30% hydrogen peroxide and 0.48 ml of an aqueous lN sodium hydroxide were dropwise added thereto. After stirring at 0C for 3 hours, the reaction mixture was extracted with an addition of ethyl acetate and saturated aqueous ammonium chloride, and the extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered, followed by concentration. The concentrate was subjected to silica gel chromatography to gi~e 2.54 g (yield 74%) of 2,3-epoxy-5-(1-hydroxy-6-methoxy-carbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-cyclopentanone.
Spectrum data H-HMR CDC13 ~
-0.03 (3H, s), 0.00 (3H, s), 0.84 (9H, s), 0.7 - 1.1 (3H, brt), 1.1 - 2.3 (20H, m), 3.4 - 3.5 (lH, m), 3.61 (3H, s), 3.68 (lH, brs), 4.0 - 4.1 (lH, m), 5.5 - 5.7 (2H, m) Examples 2 to 5 The 2,3-epoxycyclopentanones listed in Table 1 were obtained in the same manner as in Example 1.

~ - 77 -133S6~9 ~~ ~ ~ o X

$ ~I~ ~ o ;~. ~~ ,I, 1~ ~, ~, 'I, a d~ .
.~ ~

D

O C~

8 ~ 5 E ~ I

o ~
O~ I ~

q ~ ZO

- 7~ - .

-- I ~ '~ 5 ~O ~ N
~ m ~ ~ m ~" x I 0~ m ,_ N

~, ~ U, U~ ~ 11 o `_ o ;~ --S ~ o--J _ O ~ ~
I

f O ~

~ ~ Z

Ta~: 1 (Conbnued) Exam- Starting compound 2,3-epoxy y;eld NMR
ple 2-cy(lopentanones cy~Lopentanones ( % ) ( ~ C D C13 ) No .

4 O OH O OH 43 1.1-2.7 (29H, m), )~" ,COOCH3 ~ COOCH3 2.9-3.3 (lH, m), 3.3-4.4 ~0 0~0 (5H, m), 3.69 (3H, s), 4.5-5.0 (2H, m), 5.3-5.8 O _~ O ~ (2H, m) 5- ( 1-hydroxy-6-methoxy- 2, 3-epoxy-5- ( l-hydroxy-carbonylhexyl)-4-[3- 6-methu~sy~Ll)onyl- ' (tetrahydlu~yLdn-2- hexyl)-4-[3-(tetrahydro &~
yloxy)-3-cyc~Lohexyl-1- pyran-2-yloxy)-3-cycl~ C~ ~
propenyl]-2- hexyl-l-propenyl~cycl~ ~:ra cyc~opentenone pentanone ~

~ -- 80 --13356~9 ,~ ~

CO O
~ a ~ ~ o C-) ~ t'') ~ N N ~D t--~ ~ X

O ~ ~ ~

~ I

O C~

a ~ ~

. r~ ~ ~ r ~ o ~ ~ ~ 1 o ~
I I ~

X ~ Z

- 81 - 13356 ~9 Example 6 Synthesis of 2-methylthio-5-(1-hydroxy-6-methoxy-carbonylhexyl)-4-(3-t-butyldimethylsilYloxy-l-octen 2-cyclopentenone O OH
j~\\,~ COOCH3 O ~ ..
osi,~
O OH
MeS ~ COOCH3 osi ~. -A solution of sodium thiomethoxide (2.30 g) in methanol (100 ml) was cooled to 0C, acetic acid (2.82 ml) was added, the mixture was stirred for 5 minutes, Triethylamine (915 ml) was added, and a solution of 2,3-epoxy-5-(1-hydroxy-6-methoxycarbonyl-hexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)cyclo-pentanone (3.26 g) in methanol (40 ml) was added. After stirring at room temperature for 12 hours, water was added to the mixture, and the mixture extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and filtered, followed by concen-tration. The concentrate was subjected to silica gelchromatography to give 3.47 g (yield 96%) of 2-methyl-thio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyl-dimethylsilyloxy-l-octenyl)-2-cyclopentenone.
Spectrum data lH-NMR CDC13 0.00 (3H, s), 0.03 (3H, s), 0.87 (gH, s), 0.7-1.1 (3H, brt), 1.1-2.3 (20H, m), 2.33 - 82 - 1335 6~9 (3H! s), 3.1-3.3 (lH, m), 3.63 ~3H, s), 3.6-3.8 (lH, brs), 3.9-4.2 (lH, m), 5.4-5.6 (2H, m), 6.78 (lH, d, J = 3 Hz).
Examples 7 - 9 The 2-substituted-2-cyclopentenes listed in Table 2 were obtained in the same manner as in Example 6.

Table 2 Exam- 2-Substituted-2- Yi~Ld NMRple Star~ng compound -cy~Lopentenones ( % ) ( ~ C D C13 ) No .

7 O OH O OH 54 0.04(6H, s), 0.89 ~A` - COOCH3 ~ /~COOCH3 (9H,s), 1.1-2.1 0~ ~ CH3S-~ O (llH, m), 2.1-3.1 (6H, m), 2.32 (3H, s), ", OSi~ OSi ~ 3.1-3.5 (lH, m), 3.68 (3H, s), 3.8-4.0 2, 3-epoxy-5- ( l-hydroxy- 2-methylthiD 5- ( 1- ( lH, m ), 4 . 6-4 . 85 6-meth~)~y~dLbonyl-2- hydroxy-6-methoxy- (lH, m), 5.3_5.9 hexynyl) -4- ( 3-t-butyl- carbonyl-2-hexynyl) -4- ( 2H, m ), 6 . 90 ( lH, d, dimethylsilyloxy-3-cy~} (3-t-butyldimethyl- J= 3.0 Hz) C~:~
pentyl-l-propenyl) cyc~ silyloxy-3-cyclopentyl- C~
pentanone l-propenyl)-2-cyc~ Cs~
pentenone 133~669 ~ ' ~ Ct7 X CO t-- o X ~ ` ~ ~ ~ I I ~` N
z RU~ O ~ N
_ ~ -- ~ ` ~ ` o O ~ I t~ Pi x O o -- ~7 `_ _, _ _ ~ ~ _ ;~ ^ .
~ d~ O
.p _ ~D

~ ~ 4 ~ ~, ~ , ~

8 S ~ ~ ~ 4 ~ ,~, Z o~

133~ 6 G9 t--' ~i X d~
o ~ ~ ~ o Z V ~ ~

~ E; '` ~ ^ ^

o ~ ~ ~ ~ ~

~ ~, w~

E~ ~ , ~ >t ~ ' , ,~

u~ o 1' ~ -O

X ~ z a~

~ - 86 - 1335669 Example 10 Synthesis of 2-(2,3-dihydroxypropylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexYnyl)-4-(3-t-but dimethylsilyloxy-3-cvcloPentYl-l-Propenyl)-2 pentenone O OH
~ ~ _ ~ COOCH3 O /-_ OSi ~

OH O OH
HO ~ S ~ ,~ - ~ COOCH3 /

osi A 49 mg amount of 2,3-epoxy-5-(1-hydroxy-6-methoxy-carbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cyclopentyl-l-propenyl)cyclopentanone was dissolved in 1 ml of methanol and 21 ~l of triethylamine was added.
Then, 12 mg of 2,3-dihydroxypropanethiol was added thereto, followed by stirring for 2 hours. The reaction mixture was poured on an aqueous saturated solution of potassium hydrogen sulfate, followed by extracting with ethyl acetate. The extracted solution was washed with a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After filtering and concentrating, the concentrate was subjected to silica 3Q gel chromatography to give 36 mg (yield 62%) of 2-(2,3-dihydroxypropylthio)-5-(1-hydroxy-6-methoxy-carbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cycl-opentyl-l-propenyl)-2-cyclopentenone.
Spectrum data lH-NMR CDCl3 0.05 (3H, s), 0.09 (3H, s), 0.89 (9H, s), 1.1-2.0 (llH, m), 2.0-2.7 (5H, m), 2.7-3.4 (6H, m), 3.67 (3H, s), 3.4-4.0 (4H, m), 4.5-4.9 (lH, m), 5.4-5.8 (2H, m), 7.1-7.3 (lH, m) Examples 11 - 18 The 2-substituted-2-cyclopentenes listed in Table 3 were obtained in the same manner as in Example 10.

- 8~ - 13356 69 o~
O ~ O U~ a~ r C`l N
Z
~ - r r - - - - -O t~ ~ O ~ ~ m o________~

_ r_ r o O ~

C`l o o ~

~ r .
C
O
1'7 _ ~I I
~ P' _ J
.0 _~ < 1~
O ~ _ O
=

crl c ff ~
-, ~ , _~ _ L O , ' , Q ~ -. , ,... o ,~
r o-"~ , ` ,c o ~ _ ~, ~ ~ .
_I o Table 3 tContinued) Exam- Startlng compound 2-Snbstituted-2-cgclo- Yleld NMR
ple pentenones (Z) No. 2,3-epoxycyclopentanonen Thiols (~CDC13) 12 Oh 74 0.04 (6h, 8), 0.90 O I ~ COOC8 (9~ 8), 1.0-3.0 \S8 ~ ~ S- ~ (23~, ~), 3.35-3.7 OSi- (1~, m), 3.68 (3~, 8), 3.8-4.0 (1~, ~), 4.6-4.8 ~ ), 5.4-5.7 3-phenylpropane-1- 2-(3-phenylpropyl~hLo)-5-(1- (2~, ~), 6.89 (lh, thiol hydroxy-6-~e~hoxycarbonyl-2- d, J - 2.8 hz), hexyngl)-4-(3-t-butgldi~ethyl- 7.0-7.4 (5~, m) silyloxg-3-cyclopentyl-1-propenyl)-2-cyclopentenone o. ~ o o 5 CO .
o ~
o J o ~,~ ~, ol ~~ rr ~C ~ ~ ~ r~
o . ~ ,~

,~
o o r~ W ~ ~
o ~, ~ , ~ ~
,, C7 >.. 0 ~ O
C`l o ", i o ~ \ ~
o ., ~1 D ,- ~

_ o O
-C~
D

r~ O

Tsble 3 (Continued) Ex~m- St~rtlng co~pound 2-Substituted-2-cyclo- Yield NMR
ple No. 2,3-epoxycyclopentanones Thiol8 pentenones (~ CDC13) 14 Sb' Ob 85 0.08 (68, 9 ), 0.89 ~ O L - ~ COOCb3 (9H, s), 1.1-2.0 C53c S ~ z o 3.7 (55, ~), Cb O OSi ~ 3.3-3.5 (18, ~), 3.69 (3b, 5), 3.8-4.1 (2b, m), 6-~ethoxynaphtha- 2-t6-methoxynaphthgl-2-thLo)- 3.97 (3H, a), ~' lene-2-thiol 5-~1-hydroxy-6-methoxy- 4.6-4.8 (l'd, m), carbonyl-2-hexynyl)-4-(3-t- 5.4-5.8 (2H, m), bucyldim~thyl~ilyloxy-3-cyclo- 6.74 ~111, d, pentyl-l-propenyl)-2-cyclo- J - 2.7 H2), pentenone 7.0-8.1 (6b, C~

- 92 - 133S6~9 o C"
o C . , , ~ , . , C t.
O O ~ o C~
Z ~ C ~ ~ C~ C~
~ 7 n ~ R
o ~:~ ~ ~ _ ~ ~ ~ ~.~ _ o -- _ _ _ _ _ _ _ _ ~

~ _ I_ O ~ , , .,~ > S
~ > ~1- i ' O ~ >~ o O ~ ~ C
~ Ir~ A ~
0:=~ 0 . ," ~
~1 ~ _ r Ll C~

~ .
D
O

, ~ , ~_.
O ~ C
< \ l x ~.... - ,,~,,`~ .

O I .
O ~ .a K ~ z .

o t........... 2 ~ o O ~ ~ t~ ~t ~ tT~ _ _ o t~ I t~ It~2 _ _ `
t~ O O _ tO mtou~ ul ~ 1 2 ~ ~ ~ E~ ~ ~ ~ m ~_ v E C7 Ei E E ~ 2 o m m m i-- m~ m m m ~ 1 m t~l 2 d tt~ ~ t~l ~ /
t, ~ ~
O ~ , L' I
V ~> ~> L t II C
~? > ~ t~
> < I I Y
"~ ~" '' ''~
o ~ ~ ~ .~
tO l I
t t C~) ~
~ ~ tO
~ _ O~ ~

t~ ~

L m ~ . t-O ~ r t t~ ~ t~
O

~o _,/ ,~ /IA ' ' /~ ~ V
O ~
O

~ o ~o L.~
.

R R R R R
a: ~ ~ -- m a~ ~ ~ m z ~ ~ O ~_ _ v~

~ _ O ~ ~ o o u~

m o o w c~
o ~ ~ o~ ~ K

O ~, O ~) c ~_ V~
rl L

rl O
V~
~ .

~ ~ I
~ I~1 ~__ _ O
m ~ K o t~ ~ ^ ,1 ,1 o v .
~0 ~

e~l o ~ ~ ~
o ~ -- Ll R ~ .
K o. z .
133~669 a a a a a x ~, w ~ o~ w w w w Z -- ~ _ ~ _ _ o c ~ r o o c ~

~/ _ o ~
1~ l --S C

O =~

L~
C

r~
.0 U~

W .d ~ I
_l C~l 0 ~ L
O C~l ~ L~
a O co Iq .

133SG~9 _~am~le 19 S-~mtheses of 5-(6-methoxycar~onyl-1-methYlthio-hexvl~-2-methylthio-4-(1-octenyl)-2-cyclopentenone and 5-(6-~ethoxycarbonylhexylidene~-2-methylthio-4-~1-octen~l)-2-cycloPentenone o 0~ i C 3 ~ COOCH3 -(A) O SCH
CH3S ~ COOCH3 . (B) To a solution of 16.9 mg of sodium thiomethoxide dissolved in 1 ml of methanol, 39 ~l of acetic acid was added under ice-cooling and stirring. A solution of 60 mg of 2,3-epoxy-4-(l-octenyl)-5-(6-methoxycarbonyl-hexylidene)cyclopentanone in 1 ml of methanol was added, then triethylamine (144 ~l) was added, and the mixture was stirred at 0C for 4 hours. The reaction mixture was diluted with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, concentrated and then provided for silica gel.column chromatography to give 16.7 mg (yield 20%) of 5-(6-methoxycarbonyl-1-methylthiohexyl)-2-methylthio-4-(l-octenyl)-2-cyclo-pentenone and 9.0 mg (yield 13%) of 5-(6-methoxy-carbonylhexyl)-2-methylthio-4-(1-octenyl)-2-cyclo-133s6~9 pentenone.
Spectrum data (A) 1H-NMR (CDC13) 0.89 (3H, brt, J = 5.5 Hz), 1.0-2.5 (20H, m), 2.37 (3H, s), 3.68 (3H, s), 3.96 (lH, brd, J = 4.0 Hz), 4.20 (lH, dd, J = 15.0, 8.5 Hz), 4.67 (lH, dt, J = 15.0, 6.4 Hz), 6.5-6.8 (2H, m).
(B) 1H-NMR (CDC13) 0.89 (3H, brt, J = 5.0 Hz), 1.1-1.9 (16H, m), 2.06 and 2.08 (3H, s), 1.9-2.7 (5H, m), 2.37 (3H, s), 3.0-3.3 (lH, m), 3.4-3.6 (lH, m), 3.69 (3H, s), 5.36 (lH, dd, J = 15.5, 7.8 Hz), 5.61 (lH, dt, J = 15.5, 7.8 Hz), 6.87 and 6.90 (lH, d, J = 3.0 Hz).
Example 20 SYnthesis of 2-methylthio-5-(1-hydroxy-6-methoxy-carbonylhexyl)-4-~3-hydroxy-1-octenyl)-2-cyclo~entenone OH
MeS ~ ~ , ~/COOCH3 1.
osi--X

OH
MeS ~ ~ COOCH3 OH
To 350 mg of 2-methylthio-5-(l-hydroxy-6-methoxy-carbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone obtained in Example 6 was added a solvent mixture of 10 ml of acetic acid, 5 ml of tetrahydrofuran, and 5 ml of water, and the mixture was - 98 - 133S6~9 stirred for 24 hours. Toluene was then added, and after concentration, the concentrate was diluted with saturated aqueous sodium hydrogencarbonate and extracted with ethyl acetate. Subsequently, the extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concen-trated, followed by silica gel chromatography to give 178 mg (yield 65~) of 2-methylthio-5-(1-methoxycarbonyl-hexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.
Spectrum data lH-NMR CDC13 0.89 (3H, brt), 1.1-2.4 (21H, m), 2.34 (3H, s), 3.1-3.4 (lH, m), 3.65 (3H, s), 3.6-3.9 (lH, m), 3.9-4.2 (lH, m), 5.2-5.9 (2H, m), 6.79 (lH, d, J = 3 Hz).
Example 21 Synthesis of 2-methylsulfinyl-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-hydroxy-1-octenyl)-2-cyclo-pentenone O OH
1~ 1 MeS ~ ~ COOCH3 ~1 OH

O O OH
MeS ~ COOCH3 = \/
OH
To a solution of 35 mg of 2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone obtained in Example 20 dissolved in 5 ml of dichloromethane was added 17 mg of 3-chloroper-benzoic acid, and the mixture was stirred for 1 hour.
Saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. An organic layer was added, and the mixture was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated, followed by silica gel chromatography to give 7.3 mg (yield 21%) of 2-methylsulfinyl-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone.
Spectrum data lH-NMR CDCl3 0.88 (3H, brt, J = 5.7 Hz), 1.1-2.4 (21H, m), 2.34 (3H, s), 3.1-3.5 (lH, m), 3.66 (3H, s), 3.7-4.1 (lH, m), 3.9-4.2 (lH, m), 5.2-5.9 (2H, m), 7.80 (lH, d, J = 3 Hz).
Example 22 Synthesis of 2-methylthio-5-(6-methoxycarbonyl-hexylidene)-4-(3-t-butyldimethylsilYloxy-1-octenyl)-2-cyclopentenone O OH
MeS _ ~ ~ ~ ~'~ -^~_~COOCH3 ~\/

osi ~c MeS ~ ^~ \ ~ COOCH3 ~~

Osiy To a solution of 3.47 g of 2-methylthio-5-(l-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethyl-silyloxy-1-octenyl)-2-cyclopentenone obtained in Example 6 in dichloromethane (30 ml) was added dimethyl-loo 1335669 aminopyridine (1.54 g) and the mixture was cooled to0C. To the solution was dropwise added 0.59 ml of methanesulfonyl chloride, and the mixture was stirred at room temperature for 15 hours. To the reaction mixture were added ethyl acetate and an aqueous potassium hydrogensulfate, and the product was extracted into an organic layer. The extract was washed with saturated a~ueous sodium hydrogencarbonate and saturated sodium chloride, dried over anhydrous magnesium sulfate, and filtered, followed by concentration. The concentrate was subjected to silica gel chromatography to give 2.15 g (yield 64%) of 2-methylthio-5-(6-methoxycarbonyl-hexylidene)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone.
Spectrum data H-NMR CDCl3 0.00 (3H, s), 0.02 (3H, s), 0.87 (9H, s), 0.7-1.1 (3H, brt), 1.1-2.3 (18H, m), 2.33 (3H, s), 3.65 (3H, s), 3.9-4.1 (2H, m), 5.38 (lH, dd, J = 7.5 Hz), 5.65 (lH, dd, J = 15, 6 Hz, 6.5-6.8 (2H, m).
Examples 23 - 33 2-Substituted-2-cyclopentenones listed in Table 4 were obtained in the same manner as in Example 12.

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Example 34 13 356~9 Synthesis of 2-methylthio-5-(6-methoxycarbonyl-hexylidene)-4-(3-hydroxY-1-octenYl)-2-cyclopentenone o MeS ~ ~ COOCH3 osi X

MeS ~ COOCH3 I \/~/ ~
OH
An amount of 1.42 g of 2-methylthio-5-(6-methoxy-carbonylhexylidene-4-(3-t-butyldimethylsilyloxy-1-2~ octenyl)-2-cyclopentenone obtained in Example 22 was added to a mixture of acetic acid (2.1 ml), tetrahydro-furan (1.4 ml) and water (0.7 ml), and the mixture was stirred at room temperature for 2 days. To the reaction mixture saturated aqueous sodium hydrogencarbonate and ethyl acetate were added, and the product was extracted into the organic layer. The extract was washed with saturated aqueous sodium chloride, then dried over anhydrous magnesium sulfate and filtered, followed by concentration. The concentrate was subjected to silica gel chromatography to give 0.93 g (yield 85%) of 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone.
Spectrum data H-NMR CDCl3 0.89 (3H, brt), 1.1-2.4 (19H, m), 2.35 (3H, s), 3.66 (3H, s), 3.9-4.2 (2H, m), 5.2-5.9 (2H, m), 6.6-6.8 (2H, m).

~ - 113 - 1 33~6 69 Examples 35 - 44 2-Substituted-2-cyclopentenones listed in Table 5 were obtained in the same manner as in Example 34.

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~33s669 Example 45 Synthesis of 2-methylthio-5-(6-carboxyhexylidene~-4-(3-hydroxyl-octenyl)-2-cyclopentenone MeS ~ COOCH3 0~

MeS ~ ~ COOH

OH

To a solution of 345 mg o 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone obtained in Example 34 dissolved in 20 ml of acetone was added 220 ml of 0.1 M phosphate buffer of pH 8. While the mixture was stirred, 24 mg of pig liver esterase was added thereto, and the mixture was stirred at 30 - 35C for 150 hours. After the pH
was adjusted to 4 with 0.1 N hydrochloric acid, ammonium sulfate was added to saturation and ethyl acetate was added, followed by filtration. The filtrate was extracted with ethyl acetate, and the organic layers were combined and washed with saturated aqueous sodium chloride. The product was dried over anhydrous magnesium sulfate, filtered and concentrated, followed by silica gel chromatography to give 193 mg (yield 58%) of 2-methylthio-5-(6-carboxyhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.
Spectrum data ~ - 124 - 1335G~

0.86 (3H, brt, J = 5.6 Hz), 1.1-~.5 (20H, m), 2.34 (3H, s), 3.9-4.2 (2H, m), 5.2-5.9 (2H, m), 6.6-6.8 (2H-, m).
Example 46 Synthesis of 2-methylsulfinyl-5-(6-methoxYcarbonyl-hexylidene)-4-r3-hydroxy-1-octenyl)-2-cyclopentenone MeS ~ ~ ~ COOCH3 OH

O O
MeS ; ~ ~ COOCH3 ~f ~ .

OH

A solution of 252.2 mg of 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone obtained in Example 34 in dichloro-methane (20 ml) was cooled to 0C, and a solution of 3-chloroperbenzoic acid (129.8 mg) in dichloromethane (10 ml) was added dropwise thereto. After the mixture was stirred at 0C for 1 hour, ethyl acetate and saturated aqueous sodium hydrogencarbonate was added, and the product was extracted into the organic layer.
The extract was successively washed with saturated aqueous sodium chloride, saturated aqueous ammonium chloride and saturated aqueous sodium chloride, then dried over anhydrous magnesium sulfate, and filtered, followed by concentration. The concentrate was - 125 - 133~669 subjected to silica gel chromatography to give 186.8 mg (yield 71~) of a mixture of isomers of 2-methylsulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.
Spectrum data 0.89 (3H, brt), 1.1-2.4 (19H, m), 2.86 and 2.88 (3H, s), 3.67 (3H, s), 4.0-4.3 (2H, m), 5.3-6.0 (2H, m), 6.72 (lH, t, J = 7 Hz), 7.7-7.8 (lH, m).
Example 47 Synthesis of 2-methylsulfinyl-5-(6-methoxycarbonyl-hexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone MeS ~ ~ COOCH3 ~' ' I

OH

O O
MeS ~ , COOCH3 \ \~\~,~/' OH

To a solution of 21.9 mg of 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone o~tained in Example 34 in methanol (3 ml) was added a solution of sodium metaperiodide (118.7 mg) in water (0.5 ml), and the mixture was stirred for 18 hours. To the reaction mixture were added ethyl acetate and saturated aqueous sodium chloride, and the product was extracted into the organic ~ - 126 - 13~5669 layer. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered, followed by concentration. The concen-trate was subjected to silica gel chromatography to give 9.6 mg (yield 42%) of 2-methylsulfinyl-5-(6-methoxy-carbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclo-pentenone.
Example 48 Synthesis of 2-meth~lsulfinyl-5-(6-methoxycarbonyl-hexylidene)-4-(3-hydroxy-1-octenYl)-2-cyclopentenone MeS ~ ~" COOCH3 OH

O O
MeSf ~ '^\ ~ ,-COOCH3 \/~ ~
1` .
OH

To a solution of 17.6 mg of 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone obtained in Example 34 in methanol 30 (0.5 ml) was added a solution of 2KHSO5.KHSO4-K2SO4 (27.4 mg) in water (0.2 ml) at 0C, and the mixture was stirred for 30 minutes. To the reaction mixture were added ethyl acetate and saturated aqueous sodium hydrogencarbonate, and the product was extracted into the organic layer. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered, followed by concen-- lZ~ - 133~669 tration. The concentrate was subjected to silica gel chromatography to obtain 3 mg (yield 16%) of 2-methyl-sulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone.
Example 4~
SYnthesis of 2-methylsulfonyl-5-(6-methoxycarbonyl-hexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone MeS ~ ~ / \ ~ / COOCH3 \~ ~/

OH

O O
MeS ~ ~^~ ~ COOCH3 ~i ~
~H

A solution of 18 mg of 2-methylthio-5-(6-methoxy-carbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclo-pentenone obtained in Example 34 in dichloromethane (1.5 ml) was cooled to 0C, and a solution of 3-chloroperbenzoic acid (15.7 mg) in dichloromethane (1 ml) was added dropwise thereto. After the mixture was stirred at 0C for 2 hours, ethyl acetate and saturated aqueous sodium hydrogencarbonate were added and the product was extracted into the organic layer.
The extract was successively washed with saturated aqueous sodium chloride, saturated aqueous ammonium chloride and saturated aqueous sodium chloride, then dried over anhydrous magnesium sulfate and filtered, followed by concentration. The concentrate was 13356~9 subjected to silica gel chromatography to give 16.6 mg (yield 85%) of 2-methylsulfonyl-5-(6-methoxycarbonyl-hexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.
Spectrum data lH-NMR CDC13 0.7-1.0 (m 3H), 1.1-2.4 (m, 18H), 3.16 (s, 3H), 3.66 (s, 3H), 4.0-4.5 (m, 2H), 5.3-6.0 (m, 2H), 6.82 (t, J - 7 Hz, lH), 8.06 (d, J = 3 Hz, lH).
Example 50 Synthesis of 5-(6-methoxycarbonylhexylidene~-2-methylsulfinyl-4-(1-octenyl)-2-cyclopentenone MeS ~ COOCH3 ~ ~' O O
MeS ~ COOCH3 `~/~

A solution of 9 mg of 5-(6-methoxycarbonylhexyli-dene)-2-methylthio-4-(1-octenyl)-2-cyclopentenone obtained in Example lg dissolved in 2 ml o methanol, and 500 ~1 of an aqueous solution of 150 mg of sodium periodate was added, and the mixture was stirred for 5 hours. Saturated aqueous sodium chloride was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate.
After filtration and concentration, the concentrate was 133566~
subjected to silica gel column chromatography to give 4.3 mg (yield 48%) of a mixture of isomers of 5-(6-methoxycarbonylhexylidene)-2-methylsulfiny1-4-(1-octenyl)-2-cyclopentenone.
Spectrum data H-NMR (CDC13) 0.88 (3H, brt, J = 6.0 H~), 1.0-2.5 (20H, m~, 2.86 and 2.88 (3H, s), 3.67 (3H, s), 3.9-4.3 (lH, m), 5.0-6.0 (2H, m), 6.6-6.9 (lH, m), 7.80 (lH, d, J = 3 Hz) Example 51 Syntheses of 2,3-epoxy-4-trimethylsilyloxy-4-(4-phenoxybutyl)cyclopentanone and 2~3-epoxy-4-hydroxY-4 r4-phenoxybutyl)cyclopentanone O O
+
OPh O OPh OSiMe3 OSiMe3 (C) O

O -~ ~ ~ OPh OH
(D) To a solution of 2.49 g of 4-trimethylsilyloxy-4-(4-phenoxybutyl)-2-cyclopentenone dissolved in 50 ml of methanol was added 3.9 ml of an aqueous 30% hydrogen peroxide under ice-cooling and stirring. An amount of 390 ~1 of lN aqueous sodium hydroxide was added, and the mixture was stirred for 2 hours. Then saturated aqueous ammonium chloride was added, and the mixture was ~ - 130 - 1335669 extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromatography to give 892 mg (yield 34%) of 2,3-epoxy-4-trimethylsilyloxy-4-(4-phenoxybutyl)cyclo-pentanone and 1.38 g (yield 53%) of 2,3-epoxy-4-hydroxy-4-(4-phenoxybutyl)cyclopentanone.
Spectrum data (C) 1H-NMR (CDCl3~ ~
0.20 (9H, s), 1.4-2.1 (6H, m), 2.16 (lH, d, J = 17.5 Hz), 2.57 (lH, d, J = 17.5 Hz), 3.45 (lH, d, J = 2.5 Hz), 3.77 (lH, d, J = 2.5 Hz), 3.8-4.1 (2H, m), 6.8-7.1 (3H, m), 7.15-7.45 ~2H, m).
(D) lH NMR (CDC13) 1.4-2.1 (6H, m), 2.31 (lH, d, J = 16.3 Hz), 2.4 (lH, d, 16.3 Hz), 2.4-2.8 (lH, m), 3.35-3.6 (lH, m), 3.65-4.2 (3H, m~, 6.7-7.05 (3H, m), 7.1-7.45 (2H, m).
Example 52 Synthesis of 2-methylthio-4-hydroxy-4-(4-Phenoxy-butvl)-2-cvclopentenone O O

, i OPh OSiMe3 OH

To a solution of 25 mg of sodium thiomethoxide dissolved in methanol, 51 ~l of acetic acid was added, and the mixture was stirred for 10 minutes. Triethyl-amine (170 ~l) was then added, and after the mixture was stirred for 10 minutes, a solution of 16 mg of 2,3-~ - 131 - 13356~9 epoxy-4-trimethylsilyloxy-4-(4-phenoxybutyl)cyclo-pentanone obtained in Example 51 in 3 ml of methanol was added and the mixture was stirred for 5 hours. Then saturated aqueous a~monium chloride was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromatography to o~tain 7.1 mg (yield 51%) of 2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone.
Spectrum data lH-NMR (CDC13) 1.4-2.0 (6H, m), 2.18 (lH, s), 2.34 (3H, s), 2.63 (lH, d, J = 17.5 Hz), 2.72 (lH, d, J = 17.5 Hz), 4.0 (2H, brt, J = 6.0 Hz), 6.76 (lH, s), 6.8-7.1 (3H, m), 7.15-7.45 (2H, m).
Example 53 Synthesis of 2-methylthio-4-hydroxy-4-(4-phenoxy-butyl)-2-cyclopentenone O O

MeS \ ~
O OPh OPh OH OH
To a solution of 1.5 g of sodium thiomethoxide dissolved in 80 ml of methanol was added 1.8 ml of acetic acid under ice-cooling and stirring. After the mixture was stirred for 5 minutes, 4.8 ml of triethyl-amine was added, and the solution of 1.38 g of 2,3-epoxy-4-hydroxy-4-(4-phenoxybutyl)cyclopentanone obtained in Example 51 dissolved in 20 ml of methanol was added. After the mixture was stirred for 4 hours, water was added and the mixture was extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromatography to give 1.39 g (yield 83%) of 2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclo-pentenone.
Example 54 Synthesis of 2-methylthio-4-(4-phenoxybutyl~-4-trimethylsilyloxy-2-cyclopentenone O ' O

MeS ~ MeS ~
Ph ~ ~ ~\ OPh OH OSi ~
To a solution of 400 mg of 2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone obtained in Example 52 or Example 53 dissolved in 4 ml of dimethyl-formamide were added 279 mg of imidazole and 260 ~1 of chlorotrimethylsilane, under ice-cooling and stirring, and the mixture was stirred at 0C for 3 hours. The reaction mixture was extracted with an addition of water and hexane. The organic layer was washed with saturated aqueous sodium chloride, and the product dried over anhydrous sodium sulfate, filtered and concentrated, followed by silica gel column chromatography, to give 445 mg (yield 89~) of 2-methylthio-4-(4-phenoxybu~yl)-4-trimethylsilyloxy-2-cyclopentenone.
Spectrum data H-NMR (CDC13) 0.11 (9H~ s), 1.3-1.9 (6H, m), 2.35 (3H, s), 2.66 (2H, s), 3.95 (2H, t, J = 5.9 Hz), 6.80 (lH, s), 6.8-7.45 (5H, m).
Example 55 SYnthesis of 2-methylthio-4-octyl-4-trimethyl-s ilyloxy- 2-cyclopentenone - 133 _ 1335~9 o o osi os To a solution of 3.3 g of 4-octyl-4-trimethylsily-loxy-2-cyclopentenone dissolved in 50 ml of methanol was 19 added, under ice-cooling and stirring, 5.0 ml of an a~ueous 30% hydrogen peroxide, and 500 ~1 of an aqueous lN sodium hydroxide was added. After the mixture was stirred for 3.5 hours, saturated aqueous ammonium chloride was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The product was filtered and concentrated to give a crude oil of 2,3-epoxy-4-octyl-4-trimethylsilyloxycyclopentanone.
~ solution of 910 mg of sodium thiomethoxide dissolved in 100 ml of methanol was stirred under ice-cooling and stirring ~or 15 minutes. Triethylamine (6 ml) was added, and after the mixture was stirred for 10 minutes, a solution of the above crude oil of 2,3-epoxy-4-octyl-4-trimethylsilyloxycyclopentanone in 15 ml of methanol was added dropwise. After the mixture was stirred for 6 hours, the reaction mixture was poured onto saturated aqueous ammonium chloride, and the mixture was extracted with ethyl acetate. The organic 39 layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated to give a crude oil of 2-methylthio-4-hydroxy-4-octyl-2-cyclopentenone.
To a solution of the crude oil dissolved in 80 ml of dimethylformamide was added 2.2 g of imidazole, under ice-cooling and stirring, and then 2.0 g of chloro-trimethylsilane was added, followed by stirring at 0C

~ - 134 - 1335669 for 4.5 hours. The mixture was extracted with addition - -of water and hexane, and the organic layer was washed with saturated aqueous sodium chloride. After drying over anhydrous sodium sulfate, filtration and concen-tration, the concentrate was subjected to silica gelcolumn chromatography to give 1.41 g (yield 37%) of 2-methylthio-4-octyl-4-trimethylsilyloxy-2-cyclo-pentenone.
Spectrum data lH-NMR C 3 0.06 (9H, s), 0.89 (3H, brt), 1.1-1.9 (14H, m), 2.34 (3H, s), 2.64 (2H, s), 6.85 (lH, s).
Examples 56 - 60 2-Substituted-2-cyclopentenones listed in Table 6 were obtained in the same manner as in Example 55.

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~ - 140 - 1335669 Example 61 Synthesis of 2-phenylthio-4-trimethylsilyloxy-4-(4-phenoxylbutyl)-2-cyclopentenone O

o~<? ~, o ~>

OH

~S ~
~ 0~
osi- ~~
A 1.8 g amount of 2,3-epoxy-4-hydroxy-4-(4-phenoxy-butyl)cyclopentanone obtained in Example 51 was dissolved in lS ml of methanol, followed b~ adding 1.0 ml of triethylamine. Then, 790 mg of thiophenol was added, followed by stirring for 1.5 hours. The reaction mixture was poured on an aqueous saturated potassium hydrogensulfate solution, followed by extracting with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, followed by drying on anhydrous magnesium sulfate. After filtering and concentrating, the resultant crude oily product of 2-phenylthio-4-hydroxy-4-(4-phenoxy-butyl)-2-cyclopentenone was dissolved in 20 ml of dimethylformamide and, while water cooling with stirring 1.5 g of imidazole was added. Thereafter, 1.4 g of chlorotrimethyl silane was added. The mixture was stirred at 0C for 5 hours, water and hexane was added to extract. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and, after filtering and concentrating, the concentrate was subjected to silica gel column chromatography. Thus, 0.89 g (yield 37%) of ~ - 141 - 133~669 -2-phenylthio-4-timethylsilyloxy-4-(4-phenoxylbutyl)-2-cyclopentenone was obtained.
Spectrum data H-NMR CDC13 ~
0.05 (9H, S), 1.1-1.9 (6H, m), 2.63 (2H, S), 3.95 (2H, t, J = 6.0 ~z), 6.8-7.7 (llH, m) Example 62 Synthesis of 5- r 4,7-bis(t-butyldimethylsilyloxy)-1-hydroxy-2-heptenyll-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone o MeS ~
OPh OSiMe3 O OH OSi~

MeS / OSi~
~~ ~ j ~ /`OPh osi An amount of 1.195 g of 2-methylthio-4-(4-phenoxy-butyl)-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 54 was taken up, and after nitrogen replacement, 7.0 ml of dry ether and 7.0 ml of dry hexane were added.
After 857 ~1 of diisopropylethylamine was added, the mixture was cooled to -70C. A 1.0M dibutylboron-trifrate dichloromethane solution (4.57 ml) was added, and the mixture was stirred at -70C for 1 hour. A
solution of 1.47 g of 4,7-bis(t-butyldimethylsilyloxy)-2-heptenal in 10 ml of dry ether was cooled and added, followed by stirring at -70C for 3 hours. Saturated aqueous ammonium chloride was added, and the mixture was extracted with ether. The organic layers were combined, ~ - 142 -1 33s669 washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromatography to give 1.81 g (yield 75%) of a mixture of isomers o~ 5-[4t7-bis(t-butyldimethyl-silyloxy)-l-hydroxy-2-heptenyl]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone.
Spectrum data Less polar isomer lH-NMR CDCl3 ~
0-0.2 (m, 21H), 0.90 (s, 18H), 1.0-2.1 (m, lOH), 2.34 (s, 3H), 2.74 (d, lH, J
= 7.0 Hz), 3.5-3.7 (m, 2H), 3.98 (t, 2H, J
= 5.4 Hz), 4.05-4.35 (m, lH), 4.35-4.7 (m, lH), 5.5-6.2 (m, 2H), 6.7-7.1 (m, 4H), 7.1-7.5 (m, 2H).
More polar isomer lH-NMR CDCl3 ~
0-0.2 (m, 21H), 0.90 (s, 18H), 1.1-2.1 (m, lOH), 2.34 (s, 3H), 2.77 (d, lH, J
= 6.3 Hz), 3.45-3.7 (m, 2H), 3.97 (t, 2H, J
= 5.3 Hz), 4.05-4.3 (m, lH), 4.4-4.8 (m, lH), 5.5-6.2 (m, 2H), 6.7-7.1 (m, 4H), 7.1-7.5 (m, 2H).
Exam~les 63 - 71 2-Substituted-2-cyclopentenones listed in Table 7 were obtained in the same manner as in Example 62.

Tabls 7 Exa~- S~arting compound ple 2-Substltuted-2- Yield NMR~
No. 2-Sub8tituted-2-cyclopentenones Aldehydes cyclopentenones (I) (~CDCl ) 63 O O O Oh' 65 0.07 (9h, s~, 3 ~ ~ COOCb3 ~ 1.1-2.8 (22h, ~), O ~ C83S ~ COOCh3 2.35 (3h~ 8), 3.67 _ SiO ~ (38, s), 3.8-4.3 SiO (38, ~), 6.7-7.5 ~, (6h, m) 2-~eth~ltbio-4-(4-phenoxy- 3-(4-~ethox~car-butyl)-4-tri~ethyl8ilylox9-2- bonylcyclohexyl)pro- 2-methylthio-5-[1-hydroxy-3-cyclopentenone panal (4-methoxycarbonylcyclo-hexyl)propyl]-4-(4-phenoxy-bu~yl)-4-~ri~ethylsilyl-2-cyclopentenone C~

T9ble 7 ~Conclnued) Exao- Starting compound ple 2-Sub8tltuted-2- YLeld N~R
No. 2-Substi~uted-2-cyclopentenone5 Aldehydes cyclopentenone~ CDCl ) 64 0 0 OH 47 0.06 (9H, s), OCH ~ ~ OCH3 1.1-2.9 (14H, ~), ~ O ~ 2.35 (3H, s), 3.75 - SLO (3H, s)~ 3.7-4.3 (3H, m), 6.6-7.5 (lOH, m) 4-(4-metboxy- 2-meth91~h~o-5-[1-hydroxy-4-phenyl)butanal (4-~ethoxyphenyl~bucyl]-4-(4-phenoxybuty-1)-4-trl~ethyl9ilylox9-2-cyclo-pentenone C~
C~
CC:

l~bl- 7 (Co~inu-d) Ex~m- S~r~lng compound ple 2-Substltuted-2- ~ield NMR
No. 2-Substituted-2-cyclopentenones Aldehydes cyclopentenores (~ CDC13) 0 0 0 08 55 0.07 (9H, ~), S ~ ~ ~ \ ~ ~ S - ~ ~ 0.7-1.0 (3H, br~), ~ SLO ~SiO 1.0-2.0 (188, m), 2.5-2.9 (28, ~), 3.7-4.0 (18, ~), 4.0 ' (28, brt, ~' 2-phenyl~hlo-4-(4-phenoxg- Octan~l 2-phersylthlo-5-(1-hydroxy- J ~ 6.0 8z), 6.7-7.5 butyl)-4-trime~hJl~ loxJ octyl)-4-(4-phenoxybu~yl)-4- (llH, ~) 2-cyclopencenone trl~ethyl~llyloxy-2-cyclo-pentenone C~
CD

Tsble 7 (Contlnued) Exam- Starting compound ple 2-Substituted-2- Yield NMR
No. 2-Substi~uted-2-cgclopentenones Aldehydes cyclopentQnones (I) (~CDCl ) 66 0 0 0 OH 37 0.17 (9H, 8), 3 ~ COOC83 Ch3S - ~ ~f~V~ COOCH 1.0-2.1 (128, ~), ~ OCH ~ oCH 2.1-2.8 (6H, ~), _SiO OCb~3 SiO OCH3 2.35 (3H, s), 3.65 (3H, 8)~ 3.7-4.3 (lH, m), 3.86 ~, 2-methylthio-4-[3-(3,4-di- methyl 7- 2-~ethylthLo-5~ hydroxy-6- (6H, s), 6.6-7.1 '~
methoxyphenyl)propyl]-4- oxoheptanoate ~ethoxyc~rbonylhexyl)-4-~3- (4H, m) trimethylsilyloxy-2-cyclo- (3,4-di~ethoxyphenyl)propyl]-4-pentenone trimethylsLlyloxy-2-cyclo-pentenone Table 7 tContinued) Exa2- Starting co~pound ple 2^Substituted-2- Yield NMR
No. 2-Substituted-2-cyclopentenones Aldehyde~ cyclopentenones (2) (~CDCl ) 67 O O O OH 48 0.08 (9H, s), 0.83 ~ Il ~ COOCH
CH3S ~ ~" COOCH CH3S ~ 3 (9H, d, J - 4.5 Hz), ~ ~ y I ~ 0.9-2.9 (24~
- Si0 SiO 2.35 (3H, s), 3.68 (3H, e), 3 7_4 1 ` (lH, ~), 6.86 ~' 2-xethylthlo-4-(3,7-di~ethyl- ~ethyl 7- 2-~ethylthio-5-(1-hydroxy-6- (lH, 9) octyl)-4-trl~ethyl~ilylox9-2- oxoheptanoate ~ethoxycarbonylhexyl)-4-(3,7-cyclopentenone di~ethyloctyl)-4-tri~ethyl-~llyloxy-2-cyclopencenone C~
C~

C:~

Table 7 (Continued) Exam- Starting co~pound ple 2-Subqtituted-2-Yield NMR
No. 2-SubJ~ituted-2-cyclopentenones Aldehydea cyclopentenones (%) (6CDCl ) 68 0 0 0 OH 42 0.05 (9H, s), CH S ~ ~ 3 3 ~ COOCH3 0.7-1.0 (3H, brt), 1.0-2.9 (18H, ~), ~ SiO - SiO 2.36 (3H, a), 3.69 (3H, a), 3.7-4.0 (lH, m), 6.87 ~' 2-r~ethylthio-4-(1-hexynyl)-4- ~ethyl 7- 2-~ethylthio-5-(1-hydroxy-6- (lH, a) tri~ethylailgloxy-2-cyclo- oxoheptanoate xethoxycarbonylhexyl)-4-(1-pentenone hexynyL)-4-trir~ethylailyloXy-2-cyclopentenone C~

- 149 - 13356~9 o o~ o~
~ m ~ tl X ,-1 _ _ m _ q~
Z ~ _ r7 ~ ~ ~o o -- C~
o 5~ o ~ m :~ m m D:l O O _ Cl Pt c~

O ~ l l ~O~ I O
X

~0 C ~ ~ O , I~
r~
O
~d O ~t ` '<~ I<

1" 1>~ ~
I . V

~ _~
., V

V ~ O

J \ v~ r7 . ., . O ~ :~

.d 'I --O
O ~ IV~
v~

r ~ .
nl A O ~
k~

Table 7 (Contlnued) Exam- Starting compound ple 2-Substitueed-2- ~ Yleld NMR.
No. 2-Substituted-2-cyclopeneenones Aldehydes cyclopentenones ~%) (~CDCl ) O O O 08 51 0.06 (9H, 6), 1.25 3 ~ ~ ~ / COOCh3 Ch3S ~ COOCb~3 (3H, s), 1.1-2.8 Ch3 CB3 (12~, ~), 2.36 , S~0 ~ SiO (38, s), 3.68 (3~, s), 3.7-4.0 ~ ), 6.87 ~' 2-~ethylthlo-4-~ethgl-4-trl- methyl 7- 2-nethylthlo-5-(1-hydroxg-6- (1~, s) ~ethylallyloxy-2-cyclopentenone oxoheptanoaee methoxycerbonylhexyl~-4-nethyl-4-trimethylsllyloxy-2- ¦
cyclopentenot~e C~
~t C~

T~ble 7 ~Coneinued) Exam- Starein~ compound ple 2-Substituted-2- Yield NMR
So. 2-Sub~eLe~ted-2-cyolopen~e=oDeJ lldeh~de~ c3clope~no~e~ CDCI ) 71 0 0 0 OH 76 0.19 (9~, 81, 3 ~ ~ 3 3 ~ COOCH3 0.7-1.0 (3H, bre), ~ ~ \ ~ ~ 1.0-2.2 (23H, - SiO -, SiO 2.31 (2H, t, J ~ 7.2 8z), 2.35 (3H, 8), 2.45 2-~eth~lthio-4-octyl-4-trl- methy 7- 2-~ethylthio-5-(1-hydroxy-6- (lH, d), 3.67 2ethylsllyloxg-2-cyclopentenone oxoheptanoate methoxyc~rbonylhexyl)-4- (3~, 8), 3.8-4.1 octyl-4-trLmeehylsilylo~y-2- (lH, m), 6.75 cyclope~eenone (lH, s) C~
C~
S~n ~0 Example 72 Synthesis of 5-(1,4,7-trihydroxy-2-heptenyl~-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclo-pentenone O OH OSi ~

MeS ~ OSi -OPh osi--O OH OH

MeS . OH
OPh OH

To a solution of 270 mg of 5-~4,7-bis(t-butyl-dimethylsilyloxy)-1-hydroxy-2-heptenyl]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 62 dissolved in 15 ml of aceto-nitrile, 2 ml of pyridine was added. While stirring the mixture under ice-cooling, 1 ml of a hydrogen fluoride-pyridine solution was added and the mixture was stirredat 0C - room temperature for 16 hours. The mixture was poured onto saturated aqueous sodium hydrogencarbonate, and the mixture was extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel chromato-graphy to give 114 mg (yield 71%) of 5-(1,4,7-tri-hydroxy-2-heptenyl)-4-hydroxy-2-methylthio-4-(4-phenoxy-butyl)-2-cyclopentenone.
Spectrum data H-NMR CDCl ~ - 153 - 133~669 1.1-2.2 (15H, m), 2.35 (3H, s), 2.6-2.9 (lH, m), 3.5-3.7 (2H, m), 3.97 (2H, t, J
= 5.3 Hz), 4.0-4.3 (lH, m), 4.4-4.8 (lH, m), 5.5-6.2 (2H, m), 6.7-7.1 (4H, m), 7.1-7.5 (2H, m).
Example 73 Synthesis of 2-methylthio-5-~1-hydroxy-6-methoxy-carbonylhexyl)-4-hydroxy-4-octyl-2-cyclopentenone O OH

MeS ~ ~ COOCH3 i~

osi O OH

~eS / COOCH3 ~\~
OH

To a solution of ~3 mg of 2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-octyl-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 71 dissolved in 6 ml of acetonitrile was added 130 ~l of pyridine. A hydrogen fluoride-pyridine solution (260 ~l) was added, and the mixture was stirred for 18 hours. The reaction mixture was poured onto saturated aqueous sodium hydrogencarbonate, and the mixture was extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromato-graphy to give 22 mg (yield 41%) of 2-methylthio-5-(l-hydroxy-6-methoxycarbonylhexyl)-4-hydroxy-4-octyl-2-- 154 - 13356~9 cyclopentenone.
Spectrum data lH-NMR CDC13 ~
0.86 (3H, t, J = 5.7 Hz), 1.1-2.1 (24H, m), 2.2-2.5 (2H, m), 2.35 (3H, s), 2.45 (lH, d), 3.67 (3H, s), 3.8-4.1 (lH, m), 6.75 (lH, s).
Example 74 Synthesis of 5-(1,4,7-trihydroxy-2-heptenyl)-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclo-pentenone O OHOH

MeS OH
OPh OH

O OHOH

MeS ~ ~ OH
OPh OH

To a solution of 35 mg of 5-(1,4,7-trihydroxy-2-heptenyl)-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone obtained in Example 72 dissolved in 2 ml of dichloromethane was added 16 mg of 3-chloroper-benzoic acid, and the mixture was stirred for 3 hours.
3~ Saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated, followed by silica gel column chromatography to give 7.3 mg (yield 46~) of 5-(1,4,7-trihydroxy-2-heptenyl)-4-hydroxy-2-methyl-sulfinyl-4-(4-phenoxybutyl)-2-cyclopentenone.

- 155 - 13 3~ 6~9 Spectrum data lH-NMR CDC13 ~
1.2-2.3 (15H, m), 2.84 (3H, s), 2.6-3.0 (lH, m), 3.5-3.7 (2H, m), 3.95 (2H, t, J
= 5.7 Hz), 4.0-4.3 (lH, m), 4.4-4.8 (lH, m), 5.5-6.2 (2H, m), 6.7-7.1 (3H, m), 7.1-7.5 (3H, m)-Example 75 SYnthesis of 5- r 4,7-bis(t-butyldimethylsilyloxy)-2-hePtenylidenel-2-methylthio-4-(4-phenoxybutYl)-4-trimethylsi 1Y10XY- 2-cyclopentenone O OH OSi MeS ~ OSi ~ OPh osi _ O osi ~

MeS ~ ~ ~ OSi,c +
~ OPh OSi - (E) sio~,~ osi%
O
Il MeS ~ ~ (F) --f~\/~ OPh osi--To a solution of 1.00 g of 5-[4,7-bis(t-butyldi-methylsilyloxy)-1-hydroxy-2-heptenyl]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 62 dissolved in 10 ml of dichloro-~ - 156 - 13~56~9 methane was added under ice-cooling and stirring 497 mg of dimethylaminopyridene, and then 147 ~l of methane-sulfonyl chloride was added dropwise. The temperature of the mixture was gradually elevated to room temperature, and then stirred for 6 hours. Saturated aqueous potassium hydrogensul~ate was added, and the mixture was extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous sodium hydrogencarbonate and with saturated aqueous sodium chloride in the order mentioned, and dried over anhydrous sodium sulfate. After filtration and concen-tration, the concentrate was subjected to silica gel chromatography to give 644 mg (yield 66%) of low polarity isomer and 255 mg (yield 26%) of high polarity isomer o~ 5-[4,7-bis(t-butyldimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone.
Spectrum data ~ess polar isomer (F) H-NMR CDCl3 ~
0-0.1 (m, 21H), 0.90 (s, 9H), 0.93 (s, 9H), 1.1-2.1 (m, lOH), 2.36 (s, 3H), 3.4-3.75 (m, 2H), 3.98 (t, 2H, J = 6.3 Hz), 4.1-4.5 (m, lH), 6.13 (dd, lH, J = 15.0, 6.0 Hz), 6.54 (d, lH, J = 12.5 Hz), 6.63 (s, lH), 6.75-7.10 (m, 3H), 7.15-7.45 (m, 2H), 7.68 (dd, lH, J
= 15.0, 12.5 Hz).
More polar isomer (E) lH-NMR CDCl3 ~
0-0.1 (m, 21H), 0.89 (s, 18H), 1.1-2.2 (m, lOH), 2.37 (s, 3H), 3.4-3.75 (m, 2H), 3.93 (t, 2H, J = 6.3 Hz), 4.15-4.55 (m, lH), 5.9-6.5 (m, lH), 6.67 (s, lH), 6.5-7.1 (m, 5H), 7.15-7.45 (m, 2H).
Examples 76 - 84 2-Substituted-2-cyclopentenones listed in Table 8 were obtained in the same manner as in Example 75.

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Table 8 (Continued) Exam- 2-Substituted-2- Yield NMR
ple Starting compound cyclopentenone (%) (~CDC13) No.

83 O OH 0 51 0.07 (9H, s), 1.29 ~ /~v/-~COOCH3 ~ COOC~3 (3H, s), 1.1-2.4 CH3S~ ~ CH3S- ~ (10H, m), 2.36 (3H, s), CH3 CH3 3.69 (3H, s), 6.6-7.1 _SiO -SiO (2H, m) 2-methylthio-5-(1-hydroxy-6- 2-methylthio-5-(6-methoxy-methoxycarbonylhexyl)-4- carbonylhexylidene)-4-methyl-4-trimethylsilyloxy-2- methyl-4-trimethylsilyloxy-2-cyclopentenone cyclopentenone C~

O~3 ~ - 155 - 133$6~9 rn 1~
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lY

~ - 166 - 1335669 Exam~le 85 Syntheses of s-r fZ)-4,7-dihydroxy-2-heptenylidenel -2-methYlthio-4-(4-phenoxybutylidene)-2-cyclo~entenone and 5- r Z ~ -4~7-dihydroxY-2-heptenylidenel-4-hydroxy-2 methylthio-4-(4-PhenoxYbutyl)-2-cyclopentenone = sio \~\~ os O ~
Jl ~
MeS \\ ~
OPh osi _ .

~\/\ OH
O
~1 \
MeS ~ ~ +
~ ~ ~~~---- OPh , ~0 OH
~ ' MeS - ~ -OPh OH (H) To a solution of 9 ml o pyridine dissolved in 50 ml of acetonitrile was added, 4.5 ml of hydrogen fluoride-pyridine solution, under ice-coolin~ and stirring. A solution of 1.41 g of 5-[(Z)-4,7-bis-(t-butyldimethylsilyloxy)-2-heptenylidene]-2-me~hylthio-- 167 - ~

4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 75 in 15 ml o~ acetonitrile was added, and the mixture was stirred at 0C for 10 minutes, and at room temperature for 8 hours.
The reaction mixture was poured onto saturated aqueous sodium hydrogencarbonate, and the mixture was extracted ~or 3 times with ethyl acetate. The organic layers were combined, washed once with saturated aqueous sodium hydrogencarbonate and twice with saturated aqueous sodium chloride. The product was dried over anhydrous magnesium sulfate, filtered and concentrated. The oily product obtained was subject to silica gel column chromatography to obtain 158 mg (yield 20~) of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-(4--phenoxybutylidene)-2-cyclopentenone and 353 mg (yield 43%) of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone.
Spectrum data (G) H-NMR-CDCl3 ~
1.4-2.9 (m, lOH), 2.26 (s, 3H), 3.4-3.9 (m, 2H), 4.01 (t, 2H, J = 6.0 Hz), 5.83 (t, lH, J = 7.9 Hz), 6.23 (dd, lH, J = 16.0, 6.5 Hz), 6.74 (d, lH, J =11.0 Hz), 6.7-7.5 (m, 8H), 7.87 (dd, J =`16.0, 11.0 Hz).
(H) H-NMR-CDCl3 ~
1.2-2.7(13H, m), 2.33 (3H, s), 3.5-3.8 (2H, m), 3.94 (2H, t, J = 6.0 Hz), 4.15-4.50 (lH, m), 6.15 (lH, dd, J = 15.2, 6.4 Hz), 6.61 (lH, d, J = 11.4 Hz), 6.62 (lH, s), 6.7-7.0 (3H, m), 7.1-7.4 (2H, m~, 7.67 (lH, dd, J
= 15.4, 11.4 Hz).
Example 86 Synthesis of 5-[(Z)-4,7-dihydroxy-2-heptenylidenel-2-methylthio-4-(4-phenoxybutylidene)-2-cyclopentenone ~ - 168 -~sio /\~ os o ,~

MeS ~ "/ ~ -¦ ~ OPh osi _ \ ~ OH
O ,~

MeS - ~
OPh To 1.14 g of 5-[(Z)-4,7-bis(t-butydimethylsily-loxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 75 was added 40 ml of a mixture of acetic acid : tetra-hydrofuran : water = 3:1:1, and the mixture was stirred at room temperature for 18 hours. After the mixture was concentrated with an addition of toluene, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted for 3 times with ethyl acetate.
The organic layers were combined, washed successively with saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromatography to give 407 mg (yield 61%) of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutylidene)-2-cyclopentenone.
Example 87 Synthesis of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutylidene)-2-cyclopentenone ~ - 169 -1 3 3 ~ 6 6 9 o ,~

MeS ~ ~
OPh HO ~
O ~

MeS ~ ~/~
~ rJ ~ ~ OPh To a solution of 20 mg of 5-~(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxy-butylidene)-2-cyclopentenone obtained in Example 85 or Example 86 dissolved in 3 ml of methanol was added a solution of 102 mg of sodium periodate in 500 ~l of water, and the mixture was stirred for 5 hours.
Saturated aqueous sodium chloride was added, and the mixture was extracted for 3 times with ethyl acetate.
The organic layers were combined, and washed with saturated aqueous sodium chloride, followed by drying over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromatography to give 13.3 mg (yield 64%) of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutylidene)-2-cyclopentenone.
Spectrum data H-NMR CDCl3 ~
1.2-2.2 (m, 7H), 2.2-3.2 (m, 3H), 2.85 (s, 3H), 3.5-3.8 (m, 2H), 4.03 (t, 2H, J
= 6.3 Hz), 4.1-4.6 (m, lH), 6.0-6.75 (m, 2H), 6.75-7.15 (m, 5H), 7.15-7.45 (m, 3H) 7.81 (dd, lH, J = 15.0, 11.3 Hz), 8.29 and 8.36 (s, lH).

ExamPle 88 Syntheses of 5-[(Z)-4,7-dihydroxy-2-heptenyi-denel-2-methylsulfinyl-4-(4-~henoxybutylidene)-2-cyclo-pentenone and 5- r ( z ) -4,7-dihydroxy-2-heptenylidenel-2- _ methylsulfonyl-4-(4-phenoxybutylidene)-2-cyclopentenone HO ~ ~' `OH

O

MeS ~
OPh HO ~ OH
O ~

MeS ~
~ \ ~ OPh HO ~ OH

O

Me~ ~ :
O ~ OPh (I) To a solution of 280 mg of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-(4-phenoxybutylidene)-3~ 2-cyclopentenone obtained in Example 85 or Example 86 dissolved in 15 ml of dichloromethane was added a solution of 200 mg of 3-chloroperbenzoic acid in 5 ml of dichloromethane. Saturated aqueous sodium hydro-gencarbonate was added, and the mixture was extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. After filtration and - 171 - 1335669~

concentration, the concentrate was subjected to silica gel column chromatography to give 36 mg (yield 13%) of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylsulfinyl-4-(4-phenoxybutylidene)-2-cyclopentenone and 66 mg (yield 24%) of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylsulfonyl-4-(4-phenoxybutylidene)-2-cyclo-pentenone.
Spectrum data (I) H-NMR CDC13 ~
1.3-2.3 (8H, m), 2.5-2.9 (2H, m), 3.10 and 3.11 (3H, s), 3.5-3.85 ~2H, m), 4.00 (2H, t, J
= 5.9 Hz), 4.15-4.55 (lH, m), 6.0-6.75 (2H, m), 6.75-7.05 (4H, m), 7.05-7.40 (2H, m), 7.80 (lH, J = 11.3, 15.0 Hz), 8.43 and 8.51 (lH, s).
Example 89 Synthesis of 2-methylsulfonyl-5-[(Z)-4,7-dihydroxy-2-heptenylidenel-4-(4-phenoxybutylidene)-2-cyclo-pentenone HO ~ ~ OH
O ~

MeS J ~
\ ~ OPh HO ~ - OH

O /~
MeS ~J

To a solution of 20 mg of 2-methylthio-5-[(Z)-4,7-dihydroxy-2-heptenyldidene]-4-(4-phenoxybutylidne)-2-cyclopentenone obtained in Example 85 or Example 86 ~ - 172 - 13356~9 dissolved in 2 ml of methanol was added 2 ml of an aqueous solution of 60 mg of 2KHSO5.KHSO4.K2SO4 , and the mixture was stirred for 20 hours. Saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. The organic layers were combined, and washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated, followed by silica gel chromatography to give 5.6 mg (yield 26%) of 2-methyl-l~ sulfonyl-5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-(4-phenoxybutylidene)-2-cyclopentenone.
Example 90 Synthesis of 2-methylsulfonyl-5-[~Z)-4,7-dihydroxy-2-heptenylidenel-4-(4-phenoxybutylidene)-2-cyclo-pentenone HO
o ~L

MeS ~ /
, OPh HO
~ OH
O ~ .

MeS ~ ~
O ~r OPh To a solution of 6.5 mg of 2-methylsulfinyl-5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-(4-phenoxybutylidene)-2-cyclopentenone obtained in Example 87 or Example 88 dissolved in 1.5 ml of dichloromethane was added 3 mg of 3-chloroperbenzoic acid, and the mixture was stirred for 4 hours. Saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate.

- 173 - 13~5~69 The extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated, followed by silica gel chromatography to give 3.9 mg (yield 60%) of 2-methyl-sulfonyl-5-[(Z~-4,7-dihydroxy-2-heptenylidene]-4-(4-phenoxbutylidene)-2-cyclopentenone.
Example 91 Synthesis of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybut~l)-2-cyclo-pentenone osi,~

MeS ~ OSi / ~ OPh osi~

O OH

MeS ~ ~ OH
;-- oPh OH

To 255 mg of 5-[(E)-4,7-bis(t-butyldimethylsily-loxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 75 was added 20 ml of a mixture of acetic acid : tetrahydrofuran : water = 3:1:1, and the mixture 3~ was stirred at room temperature for 26 hours. After concentration with an addition of toluene, saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted 3 times with ethyl acetate. The organic layers were combined, washed successively with saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. After filtration and concentration, ~ - 174 - 1335669 the concentrate was subjected to silica gel column chromatography to give 94 mg (yield 63%~ of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methy-lthio-4-(4-phenoxybutyl)-2-cyclopentenone.
Example 92 Synthesis of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclo-pentenone O osi~

MeS ~ Si =
} ~ \ OPh osi _ O OH
Il -MeS OH
\\ I
,/ OPh OH

To a solution of 660 mg of 5-[(E)-4,7-bis(t-butyl-dimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 75 dissolved in 50 ml of aceto-nitrile was added 4 ml of pyridine, under ice-cooling and stirring. A hydrogen-pyridine solution (2 ml) was added, and the mixture was stirred at 0C for 24 hours.
The reaction mixture was poured onto saturated aqueous sodium hydrogencarbonate, and the mixture was extracted 3 times with ethyl acetate. The organic layers were combined, washed with saturated sodium chloride and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromatography to give 320 mg (yield 83~) of 5-[(E)-4,7-dihydroxy-2-heptenyli-~ _ 175 - 1 3356 ~9 dene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclo-pentenone.
Spectrum data lH-NHR CDC13 ~
1.2-2.9 ~m, 13H), 2.37 (s, 3H), 3.5-3.8 (m, 2H), 3.95 (t, 2H, J = 6.3 Hz), 4.15-4.5 (m, lH), 6.0-6.5 (m, lH), 6.67 (s, lH), 6.7-7.15 (m, 4H), 7.15-7.5 (m, 3H).
Examples 93 - 101 2-Substituted-2-cyclopentenones listed in Table 9 were obtained in the same manner as in Example 92.

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O ~n X G Z ~n Table 9 (Continued) Exam- 2-Substituted-2- Yield NMR
ple Starting compound cyclopentenone (~) ~CDC13 No.

100 O O 72 1.30 (3H, s), 1.1-2.7 ~ COOCH3 ~ COOCH3 (llH, m), 2.35 (3H, s), CH3S ~ ~ 3 ~ ~ 3.68 (3H, s), 6.6-7.1 CH3 ~ CH3 (2H, m) -SiO OH

2-methylthio-5-(6-methoxy- 2-methylthio-5-(6-methoxy-carbonylhexylidene)-4- carbonylhexylidene)-4-methyl-4-trimethylsilyloxy-2- methyl-4-hydroxy-2-cyclo-cyclopentenone pentenone - 13356~9 5~
r '`.~
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rn . p, I V
U
O ~_ O I P~ I
,0~ - ~ v o > ~ _~ X
o > / I .

O ~ ~ ,C ~
rn ~ ,., r~ r.~

~j rl) .
r~ ~ o o ~ - 185 - 13356~9 Example 102 Synthesis of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinYl-4-phenoxybut~l-2 pentenone HO
\ ~-- OH
O ~

MeS
~'~~- OPh ~ H
HO
o MeS ~ ~
`-- -- OPh OH

To a solution of 110 mg of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxy-butyl)-2-cyclopentenone obtained in Example 85 dissolved in 15 ml of dichloromethane was added a solution of 75 mg of 3-chloroperbenzoic acid in 5 ml of dichloro-methane, under ice-cooling and stirring, and the mixture was stirred at 0C to room temperature for 4 hours.
Saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted for 3 times with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromato-graphy to give 33 mg (yield 30%) of low polarity isomerand 19 mg (yield 17%) of high polarity isomer of 5-[(Z)-4,7-dihydroxyheptenylidene]-4-hydroxy-2-methyl-sulfinyl-4-phenoxybutyl-2-cyclopentenone.
Spectrum data Less polar isomer lH-NMR CDC13 ~
1.2-2.4 (13H, m), 2.84 (3H, s), 3.5-3.8 (2H, m), 3.94 (2H, t, J = 5.9 Hz), 4.1-4.5 (lH, m), 6.0-6.4 (lH, m), 6.55-7.0 (4H, m), 7.1-7.8 (3H, m), 7.70 (lH, s).
More polar isomer lH-NMR CDC13 ~
1.2-2.5 (13H, m), 2.86 (3H, s), 3.5-3.8 (2H, m), 3.95 (2H, t, J = 5.9 Hz), 4.1-4.5 (lH, m), 6.23 (lH, dd, J = 15.8, 5.5 Hz), 6.70 (lH, d, J = 11.4 Hz), 6.7-7.0 (3H, m), 7.1-7.4 (2H, m), 7.61 (lH, dd, J = 14.5, 12.0 Hz), 7.71 (lH, s) Example 103 Synthesis of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclo-pentenone HO
~ OH
O . ,~ _ MeS ~
"~~ / ~ OPh OH
HO
~ OH
O , MeS ~ ~
O OPh OH

~ - 187 - 133S6~

To a solution of 24 mg of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxy-butyl)-2-cyclopentenone obtained in Example 85 dissolved in 2 ml of dichloromethane was added a solution of 24 mg of 3-chloroperbenzoic acid in 240 ~l of dichloromethane, and the mixture was stirred for 18 hours. Saturated a~ueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromato-graphy to give 7.3 mg (yield 30%) of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopentenone.
Spectrum data lH-NMR CDCl3 ~
1.0-2.5 (13H, m), 2.14 (lH, s), 3.6-3.8 (2H, m), 3.94 (2H, t, J = 5.9 Hz), 4.1-4.5 (lH, m), 6.0-6.5 (lH, m), 6.5-7.0 (4H, m), 7.1-7.4 (2H, m), 7.4-7.8 (lH, m), 7.94 (lH,s).
Example 104 Synthesis of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinYl-4-(4-~henoxybutyl)-2-cyclo-pentenone o MeS OH

I OPh OH

~ - 188 -133~669 O OH
MeS ~ ~ ~ // " ~ l \v'~`~
OPh OH

To a solution of 71 mg of 5-[(E~-4,7-dihydroxy-2-heptenylidene~-4-hydroxy-2-methylthio-4-(4-phenoxy-butyl)-2-cyclopentenone obtained in Example 91 dissolved in 2 ml of dichloromethane was added a solution of 45 mg of 3-chloroperbenzoic acid in 2 ml of dichloromethane, and the mixture was stirred for 3 hours. Saturated aqueous sodium hydrogencarbonate was added. The mixture was extracted twice with ethyl acetate, and the organic layers were combined, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate.
After filtration and concentration, the concentrate was subjected to silica gel column chromatography to give 27 mg (yield 38%) of low polarity isomer and 25 mg (yield 35%) of high polarity isomer of 5-[(E)-4,7-dihydroxyheptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclopentenone.
Spectrum data Less polar isomer H-NMR CDCl3 ~
1.1-2.7 (13H, m), 2.85 (3H, s), 3.5-3.8 (2H, m), 3.92 (2H, t, J = 6.0 Hz), 4.1-4.4 (lH, m), 6.0-6.45 (lH, m), 6.65-7.05 (5H, m), 7.1-7.4 (2H, m), 7.71 (lH, s).
More polar isomer H-NMR CDCl3 ~
1.1-2.3 (lOH, m~, 2.3-3.3 (3H, m), 2.87 (3H, s), 3.5-3.8 (2H, m), 3.91 (2H, t, J
= 6.0 H~), 4.1-4.4 (lH, m), 6.0-6.5 (lH, m), 6.6-7.05 (5H, m), 7.1-7.5 (2H, m), 7.69 (lH, s).

~ - 189 -133~669 Exam~le 105 Synthesis of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclo- _ pentenone O OH

MeS ~ ~ ~ OH
OPh OH

O OH

MeS ~ ~ ~ OH
~ OPh OH

To a solution of 165 mg of 5-[(E)-4,7-dihydroxy-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxy-butyl)-2-cyclopentenone obtained in Example 104 dissolved in 30 ml of dichloromethane was added a solution 117 mg of 3-chloroperbenzoic acid in 5 ml of dichloromethane, and the mixture was stirred for 2 hours. The reaction mixture was poured onto saturated aqueous sodium thiosulfate, and the mixture was extracted 3 times with ethyl acetate. The organic layers were combined, washed twice with saturated aqueous sodium hydrogencarbonate and with saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. After filtration and concentration, the concentrate was subjected to chromatography to give 78 mg (yield 47~) of 5-[(E)-4,7-dihydroxy-2-heptenyli-dene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopentenone.
Spectrum data lH-NMR CDCl ~ 0 -133~669 1.2-2.5 (13H, m), 3.15 (3H, -s), 3.5-3.8 (2H, m), 3.93 (2H, t, J = 5.9 Hz), 4.1-4.4 (lH, m), 6.1-6.4 (lH, m), 6.65-7.05 (4H, m), 7.05-7.4 (2H, m), 7.99 (lH, s).
Example 106 Synthesis of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclo-pentenone and 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclo-pentenone O OH

MeS ~ ~ OH
~ OPh OH

O OH

MeS ~ ~ ~ ~ OH +
~ OPh OH

O OH

MeS _ ~ ~ ~ ~ OH
OPh OH

To a solution of 10 mg of 5-~(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxy-butyl)-2-cyclopentenone obtained in Example 91 dissolved in 2 ml of dichloromethane was added 4.8 mg of 3-chloro-perbenzoic acid, and the mixture was stirred for 16hours. Saturated aqueous sodium hydrogencarbonate was added, the mixture was extracted with ethyl acetate, and ~ - 191 -13356~9 the organic layer was washed with saturated aqueous sodium chloride. After drying over anhydrous sodium sulfate, filtration and concentration, the concentrate was subjected to silica gel chromatography to give 2.0 mg (yield 20%) of less polar isomer, 4.0 mg (yield 40%) of more polar isomer of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinyl-4-(4-phenoxybutyl)-2-cyclopentenone and 1.6 mg (yield 16%) of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclo-pentenone.
Example 107 Synthesis of 5-t(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cvclo-pentenone O OH

MeS ~ ~ ~ OH
= OPh OH

O OH

~eS ~ ~ OH
OPh OH

To a solution of 34 mg of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxy-butyl)-2-cyclopentenone obtained in Example 91 dissolved in 2 ml of dichloromethane was added a solution 33 mg of 3-chloroperbenzoic acid in 330 ~1 of dichloromethane, and the mixture was stirred for 18 hours. Saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. The organic _ 192 - 133~9 layers were combined, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromato-graphy to give 13 mg (yield 38%) of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopentenone.
Example 108 Synthesis of 2-methylsulfinyl-4-hydroxy-5-(6-methoxycarbonylhexylidene)-4-octyl-2-cyclopentenone MeS _ ~ ~ / COOCH3 W----MeS ~ OOCH3 To a solution of 12 mg of 2-methylthio-4-hydroxy-5-(6-methoxycarbonylhexylidene)-4-octyl-2-cyclopentenone obtained in Example 101 dissol~ed in 2 ml of dichloro-methane was added 6.5 mg of 3-chloroperbenzoic acid.
After the mixture was stirred at 0C for 1 hour, saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. After washing with saturated aqueous sodium chloride, the product was subjected to silica gel chromatography to obtain 7.3 mg (yield 61~).
Spectrum data 1H-NMR CDC13 ~
0.86 (3H, t, J = 5.7 Hz), 1.1-2.1 (21H, m), 2.2-2.5 (2H, m), 2.5-3.0 (2H, m), 2.87 (3H, s), 3.68 (3H, s), 6.72 (lH, t, J = 7 Hz), 7.70 (lH, s).
Example 109 Synthesis of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-methoxY-4-(4-phenoxybutyl)-2-cyclo-pentenone HO
~ OH
O ~ , MeS
OPh OH
HO
~ OH
O
Il r MeS ~ ~
~ OPh OMe To a solution of 2 mg of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-hydroxy-4-(4-phenoxy-butyl)-2-cyclopentenone obtained in Example 85 dissolved in 1 ml of methanol was added 0.5 ~1 of acetic acid, and the mixture was stirred for 24 hours. Saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, filtered and concen-trated, followed by silica gel chromatography to give 1.9 mg (yield 95%) of 5-[(Z)-4,7-dihydroxy-2-heptenyli-dene]-2-methylthio-4-methoxy-4-(4-phenoxybutyl)-2-cyclo-pentenone.
Spectrum data H-NMR CDCl 1~35669 1.1-2.1 (12H, m), 2.36 (3H, s), 3.05 (3H, s), 3.55-3.8 (2H, m), 3.93 (2H, t, J = 6.0 Hz), 4.1-4.5 (lH, m), 6.17 (lH, dd, J = 6.2 , 15.0 Hz), 6.46 (lH, d, J = 11.0 Hz), 6.S3 (lH, s), 6.7-7.0 (3H, m), 7.1-7.4 (2H, m), 7.72 (lH, dd, J = 11.2, 15.3 Hz).
Example 110 Synthesis of 5-[(E)-4,7-diacetoxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopente-none and 5- r ( E ) -4, 7-diacetoxY-2-hePtenylidene l -4-acetoxy-2-methylthio-4-t4-phenoxybutyl)-2-cyclopentenone O OH

MeS ~ ~ ~ OH
~ OPh OH

O OAc MeS ~ ~ OAc - OPh OH

O OAc MeS _ ~ OAc ~ OPh OAc (K) To a solution of 23 mg of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxy-butyl)-2-cyclopentenone obtained in Example 91 dissolved in 2 ml of dichloromethane was added 200 ~l of triethyl-amine. Under ice-cooling and stirring. 20 ~1 of acetylchloride was added, and the mixture was stirred at ~ - 195 - 13356~9 0C for 2 hours. Saturated aqueous sodium chloride was added, and the mixture was extracted with ethyl acetate.
The extract was dried over anhydrolls sodium sulfate, filtrate and concentrated, followed by silica gel column chromatography to give 11 mg (yield 43%) of 5-[(E~)-4,7-diaceto~y-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone (J) and 4 mg (yield 17%) of 5-[(E)-4,7-~iacetoxy-2-h?ptenyli-dene]-4-acetoxy-2-methylthio-4-(4-phenoY.ybutyl-2-cyclo-pentenone (K).
Spectrum data H-NMR CDCl3 ~
(J) 1.1-2.1 (llH, m), 2.01 (3H, s), 2.13 (3H, s), 2.36 (3EI, s), 3.6-4.5 (5H, m), 6.0-6.5 (lH, m), 6.69 (lH, s), 6.7-7.2 '~H, m), 7.2-7.5 (3EI, m).
(~) 1.1-2.1 (lOE~, m), 2.01 (3H, s), 2.04 (3H, s), 2.13 (3E~, s), 2.35 (~H, s), 3.6-4.5 (5EI, m), 6.0-6.5 (lH, m), 6~64 (1H, s), 6.7-7.2 (4H, m) 7.2-7.5 (3H, ~).
Example 111 Synthesis of 2-m~thylthio-5-t6-carboxyhexylidene)-4-hydroxy-4-octyl-2-cyclopentenone o MeS ~ ~ COOCH3 ~~' "
OH

MeS ~ COO¢H~

~ - 196 -133S6~9 To a solution of 16 mg of 2-methylthio-4-hydroxy-5-(6-methoxycarbonylhexylidene)-4-octyl-2-cyclopentenone obtained in Example 101, dissolved in 1 ml of acetone, 11 ml of O.lM phosphate buffer of pH 8 was added. Under stirring, 1.5 mg of pig liver esterase was added, and the mixture was stirred at 30 - 35C for 130 hours.
After the mixture was adjusted to pH 4 with O.lN hydro-chloric acid, ammonium sulfate was added to saturation and the mixture was filtered with addition of ethyl acetate. The filtrate was extracted with ethyl acetate, the organic layers were combined and washed with saturated a~ueous sodium chloride. After drying over =
anhydrous magnesium sulfate, filtration and concen-tration, the concentrate was subjected to silica gel column chromatography to give 7.7 mg (yield 47%) of 2-methylthio-5-(6-carboxyhexylidene)-4-hydroxy-4-octyl-2-cyclopentenone.
Spectrum data lH-NMR CDCl3 ~
0.86 (3H, t, J = 5.7 Hz), 1.1-2.2 (22H, m), 2.2-2.5 (2H, m), 2.36 (3H, s), 2.5-3.0 (2H, m), 6.5-6.9 (2H, m).
Example 112 Evaluation of antitumor activity Cancer cells were grown in an RPMI 1640 culture medium containing 10% of fetal calf serum.
The compound to be tested was dissolved in 99.5%
ethanol and was added to the medium so that the final concentration of the ethanol was 0.1% or less. As a control, 0.1% ethanol was used. Ll210 cancer cells were inoculated at a concentration of 1 x 105 cells/ml in the medium and were grown for 4 days. The number of live cells was determined by trypan blue staining.
The results are shown in Table 10.

o o o o , U~ ~ ~ C`i o C~
H

O
a ~ J
--I O O

r ~ I r I I I I I I
~ O
O O I ~ I ~ c~
a) ~ I J~ . C ~ C~
F . a ~, ~ a a O < ~ <
O / O

0~-~ o~ ~- ~>0 V~ O =V~ O = U~ O = tJ~= O
c~ I ~ ~ rr) m m m m Table 10(Continued) Compound to be tested IC50 (~g/ml) HO 2-methylthio-5-[(Z)-4,7-dihydroxy-2- 1.2 O )'~\v-^\ OH heptenylidene]-4-(4-phenoxybutyl)-4-CH3S ~ hydroxy-2-cyclopentenone ~~O {~
OH

HO 2-methylsulfinyl-5-[(Z)-4,7-dihydroxy-2- 1.0 ~ ~ OH . heptenylidene]-4-(4-phenoxybutyl)-4-CH3S - <\ hydroxy-2-cyclopentenone /\/~ 00 OH

HO 2-methylthio-5-[(Z)-4,7-dihydroxy-2- 3.5 O ~ OEI hep~enyli~ene]-4-(4-phenoxy~utyli~ene)-CH3S - ~ 2-cyclopentenone '~_~ ~\/\0 cr~

Table lO(Continued) Compound to be tested IC50 (~g/ml) HO 2-methylsulfinyl-5-[(Z~-4,7-dihydroxy-2- 0.1 O O ~ ~ -f~ OH heptenylidene]-4-(4-phenoxybutylidene)-CH3S - ~ 2-cyclopentenone Example 113 133S6~9 Determination (1) of bone formation activity Human osteoblast (SAM-1, 12PDL) was cultured in ~-MEM containing 10% fetal bovine serum, and when a stable growth was attained, a predetermined concen-tration of the compound was added in the presence of 2 mM ~-glycerophosphoric acid salt, foIlowed by treatment for 25 days. The cell layer was washed with Hank's solution and the alkali phosphatase activity then measured by absorption at OD410. Next, calcium and phosphorus were extracted with a 5% perchloric acid solution and quantitated, and DNA was extracted with 5%
perchloric acid at 90C, and the weight thereof quanti-tated. These evaluations were conducted according to the methods of Koshihara et al (Biochemical and Bio-physical Research Communication Vol 145, No. 2, 1987, p. 651). The results are shown in Table 11.

Table 11 - Measurement of alkali phosphatase (ALP), calcium (Ca~, phosphorus (P) per DNA

ALP Ca P
Compound OD 410 nml ~g/~g DNA ~g/~g DNA
~g DNA

Control 1.148 + 0.0500.386 + 0.2451.528 + 0.316 HO 10 M0.333 + 0.0398.847 + 1.4855.270 + 0.144 ~ OH p < 0.001 p < 0.05 p < 0.001 2-methylthio-5-[(Z)-4,7- 10 M1.447 + 0.26829.410 + 1.26315.743 ~ 0.630 C~
dihydroxy-2-heptenylidene]- p < O.001 p < O.001 p < O.01 CJ~4-(4-phenoxybutyl)-4- C5- hydroxy-2-cyclopentenone CS~

Example 114 1 33 ~6 69 Determination (2) of bone formation activity Human osteoblast (KK-3, 18PDL) was cultured in ~-MEM containing 10~ fetal bovine serum, and when a stable growth was attained, a predetermined concen-tration of the compound was added in the presence of 2 mM ~-glycerophosphoric acid salt, followed by treatment for 14 days. The cell layer was washed with physiological salt solution and the alkali phosphatase activity then measured by absorption at OD415. Then, calcium and phosphorus were extracted with a 2N
hydrochloric acid solution and quantitated. The results are shown in Table 12.

13356~9 - ~03 --.C O ~

o ~ o o~

U~
.~ o o ....
o o o o U~
¢ ~ ~ <x~
~ o o o o C~l Q~

oo r~
o o o o ~ ~ , o o o ~~ , ~ Z
o ~ ~ \ ,"
o~ < o ~' ~
\)~ o o ~

~ --2 04 ., ,,o~
~ +l ~
,~ ~ 0 cd ~ 0 ~ ~

~r~O O O
. . .
o o o P~
~ 5 ._ ~ . . .
o o o ~1 0 ~ 0 r~to E~ I I I
o o o X ~ ~

> ~r .- ~
m ~ ~ ~ I F--`
O ~ \ ._ .~' ` ~

~\, O
\~ / m ,~ ~ c~
)~0 O ~ .
.

~ - 205 - 13356~9 Example 115 Determination (3) of bone formation activity Human osteoblast (KK-3, 18PDL) was cultured in ~-MEM containing 10% fetal bovine serum, and when a stable growth was attained, a predetermined concen-tration of the compound was added in the presence of 2 mM ~-glycerophosphoric acid salt, followed by treatment for 14 days. The cell layer was washed with a physioligical salt solution and the alkali phosphatase activity then measured by absorption at OD4l5. Next, calcium and phosphorus were extracted with a 2N
hydrochloric acid solution and quantitated.
The results are shown in Table 13.

~ - 2~6 - 133~6~9 .,, :4 co ~ o r~

tn f.~ ~
O O U) f~ ~ O

,~~1 0 --I
O O O

f) ~I~
~ 5 . .
,~ O O O
fl~ ~
E~ O

l~ ~O
O O
~1 ~ ~
'7 ~ I
f C~l ~a m ~ ~ ~ f O
O O ~ O
~4Z \
O
C~~ I
) /U-) ~
f J~ ~ o 0~ ~ 4 4 ., ~

~ - 207 - 13356~9 ,i U~

~ , ,~
.
t~
~30 o o~,, .,, ,~ Ci~
~ .
o o ¢ U~
t ,(a) a~
, ~ . .
o o ,, o t"
~ 1--E~ I I
o o ~ , ~ , J , o~, , o , ~ , \ , U~ .
~I ~ < p~
~o o ~ ~ .
o ,~
o ~ ~ , t, C`l ~ ~

- 208 - 133S6~9 U~
._~ ~ o o ,C o rn ~1 a~
~0 ~ O

_l O
o O
C U~
U ~t ~
O O
~ a o d 1` ~
o o o ~
U~
< ~ d J

O ~ ~ r O = U~ = O
'~1 r,~ ~ ~ r~.

~ - 2G9 - 13356~9 U~
P~ ~ ~
~ o oo ~ ~ ~o tdU~
C, ~ ~.
C~
,~ ,~

~r cnC~ O
o -~
o o ~n . .
o o o a~
o E~ 1` ~
o o ,. ..

m~
~ I O
o o ~- o U~ ., ~ t 0~

Claims (2)

1. 2,3-epoxycyclopentanones represented by the formula (iv-a-10):

.... (IV-a-10) wherein R2 represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 10 carbon atoms, in which the substituent of the substituted group is selected from -COOR5, wherein R5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or one equivalent cation; -OR6, wherein R6 represents a hydrogen atom, an acyl group having 2 to 7 carbon atoms, a tri(C1-C7)hydrocarbonsilyloxy group, a methoxymethyl group, a 1-ethoxyethyl group, a 2-methoxy-2-propyl group, a 2-ethoxy-2-propyl group, a 2-methoxyethoxy-methyl group, a tetrahydropyran-2-yl group, a tetrahydrofuran-2-yl group, a 6,6-dimethyl-3-oxa-2-oxo-bicyclo[3.1.0]-hexan-4-yl group, an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1-C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1-C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; or an alicyclic group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1-C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; and R34 represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 10 carbon atoms, wherein the substituent of the substituted group is selected from -COOR5, wherein R5 is a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a one equivalent cation; -OR6, wherein R6 is a hydrogen atom, an acyl group having 2 to 7 carbon atoms, a tri(C1-C7)hydrocarbonsilyl group, a group which forms an acetal bond with the oxygen atom to which R6 is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1-C7) hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms; or an alicyclic hydrocarbon group which may be substituted with a halogen atom, hydroxyl group, a tri(C1-C7) hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms.

2. 2,3-Epoxycyclopentanones represented by the formula (IV-b-10):

.... (IV-b-10) wherein R34 is as defined in claim 1; and R40 represents a hydrogen atom or a protecting group of the protected hydroxyl group.