CA1335599C

CA1335599C - 2-thio-ether-2-cyclopentenones

Info

Publication number: CA1335599C
Application number: CA000616816A
Authority: CA
Inventors: Satoshi Sugiura; Atsuo Hazato; Toru Minoshima; Yoshinori Kato
Original assignee: Teijin Ltd
Current assignee: Teijin Ltd
Priority date: 1988-04-19
Filing date: 1994-02-03
Publication date: 1995-05-16
Anticipated expiration: 2009-04-19
Also published as: CA1335669C

Abstract

2-thio-ether-2-cyclopentenones are described having two substitutents in the 4-position. The 2-thio substituent is of the type R1-S- where R1 is a substituted or unsubstituted hydrocarbon group. One substituent in the 4-position is a hydroxyl or protected hydroxyl, and the second 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

This application is a divisional application of Serial No.
597,198, filed April 19, 1989, BACRGROUND OF T~E 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 prostaglandins, prostaglandins A are known to have a double bond in the cyclopentane ring; for example, prostaglandin A2 is considered to be a medicament having hypotensive activities (see E.J. Corey et al., J. Amer. Chem.
Soc., 95, 6831, 1973).
Also, since prostagl~n~;n~ 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 Unexamined 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 ~y ~

~_ - 2 _ l 3 3 5 5 9 9 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-hydrocarbon)-4-substituted-2-cyclopentenones of the formula:

O OH
/~`W' Y' wherein W' and Y' are the same as ~ and Y, respectively.
Further, it is disclosed that these compounds are useful for the treatment of malignant tumors.
Also, European Unexamined Published Patent Publication No. 0131441 (published on January 16, 1985), disclosed S-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 known to be useful as antitumor agents (Japanese Unexamined 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).

- 3 - 133~99 .
Also, prostaglandin analogues represented by the rormulz:
O OCOCH

j` ~

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, lg82; 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:
Rl R2 OCOCH3 ~/' I
CHa-CHb = CHC-C~-CH2CH2COOCH3 CH2-CHd -,''' CHe-CH2CH2CH2CH2CH3 (R3)n R and R together represent a keto group, or one thereof is a hydrogen group and the other is hydroxy group, R is a hydrogen atom or acetoxy group, n is 0 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 Unex~m;ned Patent Publication (Kokai) No. 59-184158 disclosed, as a compound having a similar antiinflammatory activity, culavulon derivatives of the formula:

-O OAc CH-CH=CH-CH-CH2CH2COOCH3 '~;\ I
--CH2-CH=CH-CH2CH2CH2CH2CH20AC
OAc wherein Ac denotes an acetyl group.
Japanese Unexamined Patent Publication (Kok2 ) l~ No. 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:

~1 .

(Journal of the American Chemical Society (J. Am. Chem.
Soc.), 106, 3384, 1984).
Nagaoka et al similarly synthesized culavulo-.
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 ' I
COOME
,/~~ i -- ~\ OAc Cr and the for~u'l 2:
O OAc OAc COOME

C -`j\ OAc \-- ~ /\
OK

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).

.
Alsc, ~ublished PCT Patent Application No. W085-03706 (~blication date: August 29, '985) disclosed punagl-ndins represented by the follcwing formula:
~, oR2 COOR
Cl ~\ ¦ oR3 ~ .
R O
wherein R1 reprecents a hydrogen atom, C1 - C1Q an alkyl group or one equl~-alent cation, R , R , R may 3e the same or differer._, and each represents a hydroc~n atom or C2 - C10 acyl croup, and the representation _ _ 3 denotes a single ~ond or double bond, and that .hese punaglandins are useful for the therapy of mali-nant tumors.

-~ zsanori ~ukushima et zl -e or~ed ~ he compounds of the fcilow-ing formula inclu~ec in ~he a~cve formula: ~
O AcO OAc ~ ~COOCH3 C1 ~
,~ .
0~ .

have an antitumor activity (see Mas2nori Fukushima et al collected gists of the 43rd Meeting of Japanese Society of Cancer, p. 258, 1984).
Furthér, Japanese Unexamined Pztent Publi-lS cation (Kokai) No. 62-96438 disclosed 4-hydroxy-2-cyclopentenones which are culavulon analogues and punaglandin analogues of the formula:
A I

\ 3 OR
wherein X represents a hydrogen atom or a halogen atom;
A and B represent a combination of A which is 2 hydrogen atom and B which is a hydroxyl group or A and B are bonded mutually to represent one bonding arm; Rl represents a substituted or non-substituted al~yl group, and an alkenyl group or 21kynyl 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 hydrosen atom or a protective group for a hydroxyl group; with the proviso that R cannot be 2-octenyl, 8-acetoxy-2-octenyl 3~ or 2,5-octadienyl and that these compounds are useful for the therapy of malign2nt tumors.
Furthermore, the bone metabolism of zn aver2ge 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.
Koshihara 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 12_ prostaglandin Jz 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-substituted-2-cyclopentenones represented by the formula (I-c-l):

R1 5 ~ (I-c l!
~ R34 o~
wherein R1 represents a substituted or unsubstituted hydrocarbon group having 1 to 10 carbon atoms in which the substituent of the substituted group is selected from a hydroxyl group, a tri(C1-C7)hydrocarbonsilyloxy group, a halogen atom, an alkoxy group, an acyloxy group, an acyl group, an alkoxycarbonyl group and a carboxyl group; *4 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 Rs 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(Cl-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, 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 l to 4 carbon atoms; or an alicyclic hydrocarbon group which may be substituted with a -1 33~99 - 8a -halogen atoms, 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 alkoxy-carbonyl group having 2 to 5 carbon atoms, an alkoxycarbonylgroup 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 protecting group of the protected hydroxyl group.
10As part of the related subject matter there is provided a 2-substituted-2-cyclopentenones represented by the formula (I):
B A
Rl-S \j R . . . ( I ) x wherein A is a hydroxy group or () m 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;
R2 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.

- g - 1 335599 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
R -S _ ~ ~ R2 .... (I-b') ()n ~ R3 X

wherein R1, R2, R3, X and n are as defined above; when A is (1l)m - - -S-R
and B is a hydrogen atom, the above formula (I) represents 2-substituted-2-cyclopentanones represented by the following formula (I-b"):
()m S-R
O H I

Rl_s ~ R2 .... (I-b") ()n ~ 3 wherein R1, 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):

- lo - 1 3 3 5 5 9 9 o R1_S \~// ~R2 .... (I-c) ( O ) ~

wherein Rl, R2, R3, X and n are 2S C ~ined above, and the representation ~~~ denotes thar the substituent bonded to the double bond is in an r-configuration or a 1~ Z-configuration or a mixture thereof at any desired ratio.
In the above formula (I), R1 re?resents 2 substi-tuted or non-substituted hydrocarbon group having 1 to 10 carbon atoms. Examples of the non-subs~ituted 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 sroups such as phenyl, p-tolyl, 1-naphthyl, 2-naphthyl groups, and the like. The hydrocarbon group may be substituted with a plural different substitution groups. The substituents on such hydrocarbon groups include a hydroxyl group; tri(Cl - C7)hydrocarbonsilyloxy groups such as trimethylsilyloxy, t~iethylsilyloxy, 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 Rl represents alkyl 3S groups having 1 to S carbon atoms such as methyl, ethyl, propyl, butyl, and pentyl groups, and phenyl groups, particularly preferably, a methyl g~oup.

_ - ~.1 - 1 3 3 5 5 9 9 1. ~ne 2scve formulz (I), m znd n 2-~ .e same o-di_ er^-.t anc represent 0, ~ or 2. The su~c_ituent R -S- or R1-S-il 11 (O)m (O)n _ reJ=esents 2 hydrocar~on~hio g~oup when m c- n is 0, a hyd-occ-bonsulfinyl group when m or n is 1, ~nd a hyd-ocz-bonsulfonyl sroup when m or n is 2.
Ir the above formulz (I), R2 represen~_ a substi-tute~ cr non-substituted zliphatic hydroca-_on group 1~ having 1 to 10 carbon atoms. Examples o~ ~ non-subs~it-ted aliphatic hydrocarbon sroup hav-ng 1 to 10 carbon 2toms include alkyl groups such as m-_nyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, 1_ 3,7-dimethyloctyl, nonyl or decyl groups; a_`cenyl groups such as vinyl, l-propenyl 2-propenyl, l-but^-.yl, 1,3-butadienyl, 2-butenyl, l-pentenyl, 2-per enyl, l-hexenyl, 2-hexenyl, l,S-hexadienyl, 3-hex_-yl, l-heptenyl, l-octenyl, 1,7-octadienyl, l-no..enyl or 2~ 1-dece~yl groups; and alkynyl groups such 2' ethynyl, l-propynyl, 2-propynyl, l-butynyl, 3-buten- -ynyl, 2-butyr.yl, l-pentynyl, 2-pentynyl, l-hexyny , 2-hexynyl, 5-hexen-1-ynyl, 3-hexynyl; l-heptynyl, l-oc--~yl, 7-octen-1-ynyl, l-nonynyl or l-decynyl grou~s. The aliphatic hydrocarbon group may be substitut-d with plural different substitution groups. The substitutent on such aliphatic hydrocarbon groups includes -CooR5 (wherein RS represents a hydrogen atom, an zlkyl group having 1 to 10 carbon atoms or one equivalent cation); _oR6 (wherein R6 represents a hydrocen atom; zn acyl group having 2 to 7 carbon ator.s; a tri(Cl - C7)hydrocarbonsilyl group; a group -~nich forms an zcetal bond together with the oxygen atom _o which R6 is bond~d, an aromatic hydrocarbon group whicn may be substituted with a halogen atom, a hydroxyl 5-oup, a tri(Cl - C7)hydrocarbonsilyloxy group, a ca-~oxyl group, an 2cyloxy group having 2 to 7 carbon atoms, 2n acyl - 1~ 1 3 3 5 5 9 9 .
g_oup haviny 2 tc 7 cz_bon 2tcms, an alkcxyc2r~G~yl croup hav ns 2 to ~ ca=bon atoms, an alkyl group ha~ing 1 to 4 carbcn atoms, 2nd an alkoxy group havlns i to 4 carbon atoms); an 2romatic hvdrocarbon group which may be substituted wi_h a halogen a.om, 2 hyd-oxyl group a tri(Cl - C7)hydroc2-bonsilyloxy group, 2 carbcxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxyc2-bonyl group having 2 to 5 carbon atoms, an alkyl group having 1~ 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alicyclic sroup 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 c2rbon atoms, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms. Examples of RS 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 e~uivalent 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 , 1/2Ca2 , 1/2Mg2 , 1/2Zn2 , 1/3A13 . Preferably, R represents a hydrogen atom, methyl group, and ethyl group.
Examples of R in -OR include a hydrogen atom;
3~ acyl groups having 2 to 7 carbon atoms such as acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, hexanoyl, heptanoyl, and benzoyl groups; tri(C1 - C7)-hydrocarbonsilyl groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenyl-3~ silyl, and tribenzylsilyl groups; and groups which forman acetal bond togethe_ with the oxygen atom to which R
is bonded such as-metho~ymethyl, 1-ethoxyethyl, -2-met~oxy-2-propy', ~--thoxJ-2-propyl, 2-methoxyet.
- methyl, tetrahyd-_py-~ -2-yl, tetrahycrofurzn-2-yl, an~
6,6-dimethyl-3-oxa-2-oxo-bicyClo[3.1.0]hexan-4-yl groups. Exam?les cf Ihe arom2tic hydroc2rbor.s whicn mzy S be substituted wi~h z hzlogen 2tom, z hydroxvl g-~u?, a tri(Cl - C7)hydrocarbcnsilyloxy group, z car~oxyl c=_up, an acyloxy group havir.g 2 to 7 carbon atoms, an ac-;' group having 2 to 7 carbon atoms an alkoxycarbonyl group ha~ing 2 to 5 carbon 2toms, or an alkyl group havins 1 to 4 carbon atoms are phenyl, 1-naphthyl, 2-naphthyl, and 1-anthranyl. Examples of the substituent are z halogen atom such as fluorine, chlorine, and bromir~; a hydroxyl group; tri(C1 - C7)hydrocarbonsilyloxy grcups such as trimethylsilyloxy, triethylsililoxy, lS t-butyldimethylsilyloxy, t-butyldiphenylsililoxy, and tribenzylsilyloxy grou2s; a carboxyl group; an acylsxy groups such as acetoxy, propionyloxy, butyryloxy, isobutyryloxy, valeryloxy, isovaleryloxy, hexanoyloxy, heptanoyloxy, and benzoyloxy groups; acyl groups sucn zs acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, hexanoyl, heptanoyl, and benzoyl groups;
alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, and s-butoxycarbGnyl 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, R6 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 R2 is an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, tri(C1 - C7)hydrocarbon~ilyloxy 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 ln with a halogen atom, a hydroxyl group, tritC1 - 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 such an alicyclic group are cyclobutyl, cyclopentyl, cyclohexyl, l-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 fluorine, chlorine, and bromine; a hydroxyl group; tri(Cl - 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 - l 3 3 5 5 9 9 groups. Particularly preferably, 4-hydroxycyclohexyl, 3,5-diacetoxycyclohexyl, cyclopentyl, and 3-ethylcyclopentyl can be exemplifie~.
In the above formula (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

R -S ~ ~ R2 ... (I') ()n ~ R34 Il X

wherein A, B, R , R2 and n are as defined above; R
represents a substituted or non-substituted aliphatic hydrocarbon group having l to lO 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

Rl-S " ~ R2 ... (I") () ~ ~_ R33 ~ - 16 - l 3 3 5 5 9 9 wherein A, B, Rl, R2, n and the representation are as defined above; R33 represents a hydrogen atom or a substituted or non-substituted aliphatic hydrocarbon group having l to 9 carbon atoms.
R34 in the above formula (I') represents a substituted or non-substituted aliphatic hydrocarbon group having l to lO carbon atoms, and examples of such R3- include the same groups as mentioned above for R2, also including the substituents.
X1 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(Cl - 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, Xrepresents 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 l 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 l 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, l,3-butadienyl, 2-butenyl, l-pentenyl, 2-pentenyl, l-hexenyl, 2-hexenyl, l,5-hexadienyl, 3-hexenyl, l-heptenyl, 2,6-dimethyl-he?tenyl, l-octenyl, l,7-octadienyl or l-nonenyl groupsi ~ 1 3 3 5 5 9 9 and 21kynyl groups such 2_ e-hynyl, 1-propynyl, 2-propynyl, l-b~tynyl, 3--~ten-i-ynyl, 2-butynyl, 1-pentynyl, 2-pentynyl, l-:~exy.-.yl, 2-hexynyl, 5-he.~en-l-ynyl, 3-hexynyl, l-hep-ynyl, I-octynyl~ 7-octen S cr 1-nonvnyl grou~s.
Examples of 2-substituted- 2-cyclopentenones represented by the above-mentioned formula (I) include the compounds set forth below.
(1) 2-methylthio-S- i-hyc_oxy-6-methoxycarbonyl-1~ hexyl)-4-(3-t-butyldimeth-~-lsily_oxy-1-octenyl)-2-cyclo-pentenone (2) 2-methyLthio-5-~ -hyd~oxy-5-methoxycarbonyl)-4-(3-hydroxy-1-octenyl)-2-eycLo?entenone (3) 2-methylsulfinyl-.-(1-îydroxy-6-methoxy-carbonyl-hexyl)-4-(3-hydr^:~y-1-cctenyl)-2-cyclopentenone (4) 2-methylsulfony -5-(1-hydroxy-6-methoxy-carbonylhexyl)-4-(3-hydrc:-.y-1-octenyl)-2-cyclopentenone ~5) 2-methylthio-5-~:-hyd-oxy-6-carboxyhexyL)-4-(3-hydroxy-1-octenyl)-2-cy_loper.~enone (6) 2-methylthio-5-~5-methoxyc2rbonylhexylidene)-4-(3-t-butyLdimethylsilyl~.Yy-l-octenyl)-2-cyclopentenone (7) 2-methylthio-5-(~-methoxycarbonyLhexyLidene)-4-(3-hydroxy-1-octenyL)-2-cyclopentenone (8) 2-methylsulfiny~-5-(6-~ethoxycarbonylhexyli-- 25 dene)-4-(3-hydroxy-1-octe.-yL)-2-cycLopentenone (9) 2-methylsulfony'-5-(6-methoxycarbonylhexyli-dene)-4-(3-hydroxy-1-octe-.yl)-2-cyclopentenone (10) 2-methylthio-s-(5-methoxycarbonylhexylidene) 4-(3-actetoxy-1-octenyl)-3-2-cyclopentenone (11) 2-methylthio-5-(~'-carboxyhexylidene)-4-(3-hydroxy-1-octenyl)-2-eyclopentenone (12) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(1-octenyl)-2-cyclopent~none (13) 2-methylsulfiny -5-(6-~ethoxycarbonylhexyli-dene)-4-(1-octenyl)-2-cyc opente?one (14) 2-methylsulfcny -5-(6-methoxycarbonylhexyli-dene)-4-(1-octenyl)-2-cyc ~pentenone - 18 ~ l 3 3 5 5 9 9 ~ ;.) 2-methylthio-5-(5-c2~boxyhexyl ~ene)-4-(l-oc-e~-;l)-2-cyclopentencne ! - ~ ) 2-~ethylthio-5-(1-methyltnio-6-met:ncxy-c~r,ic.-ylhexylidene)-4-(1-octeny'`-2-cyclc?entsnonc (: ) 2-methylsulfinyl-5-(1-methylsu' lny'-6-~ethcx-.yczrbonylhexylidene)-4-(1-octenyl)-~-cy_'c-~en~_..one (18) 2-methylsulfonyl-5-(l-methylsul onyl-o-methcxycarbonylhexylidene~-4-(1-octenyl)-2-cyclo-l~ pentenone (19) 2-ethylthio-5-(1-hydroxy-6-methoxycarbonyl-hexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclo-pentenone.
(20) 2-ethylthio-5-(6-methoxyc~rbonylhexylidene)-lS 4-(3---butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone (2 ) 2-ethylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (2~) 2-ethylsulfinyl-5-(6-methoxycarbonylhexyli-dene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone (23) 2-ethylsulfonyl-5-(6-methoxycarbonylhexyli-dene)-'-(3-hydroxy-1-octenyl)-2-cyclopen~enone (24) 2-ethylthio-5-(6-carboxylhexylidene)-4-(3-hydroxv-l-octenyl)-2-cyclopentenone (25) 2-phenylthio-5-(8-ethoxycarbonyloctylidene)-4-[3-(~etrahydropyran-2-yloxy)-1-octenyl~-2-cyclo-pentenone (25) 2-phenylthio-5-(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-ethoxycarbcnyloctyli-dene)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone (2g) 2-phenylthio-5-(8-carboxyoctylidene)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone (30) 2-(S-methoxycarbonylpentylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-t-butyld~methylsily-loxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone - 1~ - 1335599 -(31) 2-(5-methoxycarbonylpentylthio)-5-(1-hydroxy-6-methoxycarbonyl-2-hexynyl)-4-(3-hydroxy-3-cyclo-pentyl-1-propenyl)-2-cyclopentenone (32) 2-(5-methoxycarbonylpentylthio)-5-(6-methoxy-S carbonyl-2-hexynylidene)-4-(3-t-butyldimethylsilyloxy-3--cyclopentyl-l-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-l-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-1-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 (3~) 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-~ 1 3 3 5 5 9 9 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-propenyl)-2-cyclopentenone (48) 2-(6-methoxynaphthyl-2-sulfinyl)-5-(6-methoxy-carbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2cyclopentenone (49) 2-(6-methoxynaphthyl-2-sulfonyl)-5-(6-methoxy-carbonyl-2-hexynylidene)-4-(3-hydroxy-3-cyclopentyl-1-propenyl)-2-cyclopentenone (50) 2-(4-chlorophenyImethylthio)-5-(1-hydroxy-6-methoxycarbonyl-5-hexenyl)-4-(3-hydroxy-5-methyl-1-nonenyl)-2-cyclopentenone (51) 2-(4-chlorophenylmethylthio)-5-(6-methoxy-2S 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-propenyl]-2-cyclopentenone (55) 2-ethylthio-5-(6-methoxycarbonylhexylidene)-- 2~ - l 3 3 5 5 9 9 4-[3-(tetrahydropyran-2-yloxy)-3-cyclohexyl-1-propenyl]-2-cyclopentenone (56) 2-ethyithio-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 `
(73) 2-methylthio-5-(4,7-dihydroxy-2-heptenyli-dene)-4-(4-phenoxybutylidene)-2-cyclopentenone (74) 2-methylsulfinyl-5-(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-methylsulfinyl-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-[4-(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 3~ (88) 2-methylthio-5-(1-hydroxy-6-methoxycarbonyl-hexyl)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclopentenone (89) 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclo-pentenone (90) 2-methylsulfinyl-5-(6-methoxycarbonylhexyli-S dene)-4-[3-(3,4-dimethoxyphenyl)propyl]-4-hydroxy-2-cyclopentenone (91) 2-methylsulfonyl-S-(6-methoxycar~onylhexyli-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-S-(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-2S dene)-4-(1-hexynyl)-4-hydroxy-2-cyclopentenone (100) 2-methylthio-5-(1-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 - 24 - l 335599 --(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-methoxydecyli-dene)-4-benzyl-4-hydroxy-2-cyclopentenone (117) 2-(3-acetylphenylmethylthio)-S-[1-hydroxy-4-(4-chlorophenoxy)butyl}-4-(1-octenyl)-4-hydroxy-2-cyclopentenone (118) 2-(3-acetylphenylmethylthio)-5-[4-(4-chloro-phenoxy)butyl]-4-(l-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-ll):

-O OH
R1_s ~ R2 .... (I-b-11) wherein R1, 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 R is bonded; an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl sroup, 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(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; 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 .
the following formula (III-a):

O OH

~ R21 .... (III-a) wherein R21 and R31 represent an aliphatic hydrocarbon 1~ 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 is an acyl group having 2 to 7 carbon atoms; a tri(Cl - C7)hydro-carbonsilyl group; a group which forms an acetal bond lS together with an oxygen atom to which R61 is bonded; an aromatic.hydrocarbon group also may be substituted witha 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 carbonatoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; or an alici~clic 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 epoxydization reaction to obtain 2,3-epoxycyclopenta-nones of the following formula (IV-a-l):

`_ - 27 _ 1 335599 OH

~,,1 ~ R21 \ ~ .... (IV-a-1) 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 ~asic compound, a alumina or si~ica 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 formula (III-a), R21 and R3 represent an aliphatic hydrocarbon group having l 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(Cl - 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(Cl - 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 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 havins 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, ar. acyl group having 2 to 7 carbon atoms an alkoxycarbonyl group lQ 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. As specific examples of R2 and R31, the same specific examples as described above for R2 and R3 in the above formula (I), respectively, can be included.
lS In the process of the present invention, the compounds of the above formula tIII-a) are subjected to epoxydization reaction. As the reagent for the epoxydization reaction, an alkylhydroperoxide such as t-butylhydroperoxide or hydrogen peroxide mzy be used, but preferably hydrogen peroxide is used. Although anhydrous hydrogen peroxide may be used, a O 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, preferably 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 _ 1 3 3 5 5 9 9 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 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 S 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-1) can be isolated and purified by a conventional means such as extraction, washing, drying, concentration, and chromatography, but the unpurified reaction mixture also can 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 thç 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.

-In the abovè formula (V), R1 represents z substi-tuted or non-substituted hydrocarbon having 1 to 10 carbon atoms. Specific examples of R1 incIude those which are the same as the specific examples described for the above formula (I).
When a basic compound is used in carryins out the reaction between the 2,3-epoxycyclopentenones of the above formula (IV-a-l) and the thiols of the formula (V), such basic compounds are preferably alk21i 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 benzyl trimethyl ammonium hydroxide.
Particularly preferably, the above tertiary aminessuch 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-l). 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 ~ 1 3 3 5 5 9 9 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 / y ~ R21 -~ b-10) \R31 wherein Rl, R2l 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 ~lxture can be subjected as such to oxidation reaction, deprotection reaction and/or protection reaction without isolation of - 20 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 suloxide preferably include peracids such as hydrogen peroxide, peracetic acid, perbenzoic acid, and m-ch1oro-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 - 1 3355~9 1,2-dicycloroet~2ne, `~enzene, anc e_hyl ac~tate 2~e used.
Pref2r2bly the r^-ction t~mpe~ature is withi.~ -78C
to 50C, more pre_erably -20C to 30C.
The reaction time may dif~er de?endinc on the starting compounà, the re2ction temperature, znd he kind of oxidizing agent, but prefer~Dly is 30 minu~es to 38 hours.
For example, when a sulfoxide is to be produced by 1;J using an oxidizing agent which can produce both sul.oxide and sulfone, preferably the amount of the oxidizing agent is not enough to produce sulfone, for exzmple, an amount of about 1 to about 1.5 equivalents relative to the (I-b-10) used, and the reaction is lS monitored by thln layer chromatogr2pny (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.
2~ Further, a desired compound having protective groups in the molecuIe 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, dioxane, acetone, and acetonitrile. Preferably the reaction is carried out 2t a temperature of from -78C
to +30C, 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 _ 1 335599 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 S hydroxyde, and calcium hydroxide, or a water-alcohol mixture or a methanol or ethanol solution containing 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 E~ 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 protecti~e group is a tetrahydropyran-2-yl group, - 3~ -tet=ahydrofu~2rn-~-Y' c-~u , cr l-^~hcxyet.~ c-_~-, =. e prot~cti~e g~oup c~n he int~oduc~d by plZci~s ~;~e compound in contac- -~ith dlhydropyr~ne, d hyd_oLur2n, O-ethyl vinyl ether, whic;~ is 2 cor~_s~ondi~c ~inyl o~h~--5 compound, ln the presence of an 2C' dic c2t21yst such as p-toluenesulfonic 2cld, 2nd thus novel 2-SUDStituted-2-cyclopentenones repr~sented by the a~ove for~ul~
(I-~-11) are 2re~2 ed.
When alumina or s lic2 gel is used during the 1~ reaction between the 2,3-epoxycyclopentenones of the abo~e formula (IV-a-1) and the thlols of the formula (V), such alu~ina or silica gel may be silica gel or alumina used generally during a se~ar2tion and purification of an organic compound. For the silica gel, for example, *Wakol Gel C-300, *W2kol 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 reaciion, preferably an inert -solvent is used. As the solvent, any inert sol~ent which can dissolve the starting compound may be used, but preferably alcohols such as methanol ~nd ethanol, ethers such as ethyl ether and tetrahydrofuran, and hydrocarbons such as hexane and benzene are emp~oyed.
The amount of the solvent should permit the reaction to proceed smoothly, ~ut preferably 1 to 100-fold volumes of tne starting materi21, more preferably 2 to 20-fold volumes are employed.
The amount of the thiols (V) to be used in the present in~ention is preferably stoichiometrically equimolar to the st2rting material (IV-a-1). The si liC2 gel and alumin2 which catalyse the reaction is prefer2bly used in an 2mount of 0.1 to 20-Lold weish~, more prefer2bly 0.5 to 5-fold weish~, relative to the star~ing materi21 (IV-2-1).

*Trade mark _ 35 _ 1 3 3 5 5 9 9 -P~e erably, the re2ction tem~e_atu-- is wit~in -20 to 100~C, more ?referably 0 to 30C. T~e reactio~ time may di_fer depe~ding on the catalys~ amcunt and the solvent used, but preferably the re2ctisn is completed S ~ithin 10 minu~es to 24 hours After the reaction, the 2-substitu ed-2-cyclo-pentencnes represented by the above for~ul2 (I-b-l0) can be obtained only by filtering the reac__on mixture to remove alumina and silica gel, and evapo-ating the reaction solvent, but for a further pur__ication, 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).

R1-S ~~ 2 (I-a-1) ()n R34 wherein Rl, R2, R34 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 followingformula (I-b-lO):
O OH

R1-S ~ ~ ~21 (I-b-10l - 36 _ 1 335599 wherein Rl, R21 and R31 are as defined above, and subjecting the dehydrated product to oxidation, deprotection reaction and/or protection reaction.
In the above formula (I-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 and R3 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 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(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. In the above formula (I-b-10), specific examples of R21 and R31 include the same specific examples as ~ 37 ~ l 335599 desc-_bed for R2 ana R3 in the above formula (I).
In the process, the comDounds of the a~ove formula (I-b-10) a-e sub~ected to dehydr2tion reaction. Dehydration reaction is - prefe-aDly ca--ied out by usina a baslc compound and 2 reactive derivztive of an organic sulfuric acid. More specLfically, the compound of the above formula ( I-D-1O ) 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-11), and then elimination of an organic~sulfonic acid.
Prefera~ly, amines are used as the basic compound - together with the derivative 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, znd DBN.
2- Examples of reactive derivatives of organic sulfonic acid include organic sulfonic acid halides such as methanesulfonylchloride, ethanesulfonylchloride, n-butanesulfonylchloride, t-butanesulfonylchloride, trifluoromethanesulfonylchloride, benzenesulfonyl-3 'J 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.
3- The basic compound itself as mentioned above may be also used as the solvent, but preferably halogenated hydrocarbons such as dichloromethane, chloroform, carbon 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-IO).
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 sol~ent 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, 3n 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):

- 3~ -1 3~5599 o Rl-S _ ~ ~21 .... (I-a-10) wherein Rl, R21 R3l and the representation r ~ are 25 defined abo~e.
As the basic compound which can be used in the l~ 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 lS 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 e~traction, washing, concentration, 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-l) 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-ll) from the 2-substituted-2-cyclopentenones represented by the above formula (I-b-lO).
Of the 2-substituted-2-cyclopentenones of the above formula (I), the Z-substituted-2-cyclopentenones represen-ted by the above formula (I-a-l) and the 2-substituted-2-cyclopentenones A O _ 1 3 3 5 5 9 9 -represented hy the foilowing for~ula (I-b-12`:

()m ii 1 O S-R-Rl-S ~ R2 .... (I-b-12) ()n R34 wherein R1, R2, R34 and n are as defined above and m is 0, 1 or 2 can be produced by allowing 2,3-epoxy-cyclopentanones represented by the following formula (IV-a-2):
O
-/\f~ ~ R21 / \ / .... (IV-a-2) ~ 31 R
wherein R 1, R31 and the representation ~,v~~ 2re as-defined above to react with thiols represented by the -following formula (V):
Rl-SX .... (V) wherein Rl is the same as defined above in the presence of a basic compound, alumina or silica gel, a-Ld 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, znd 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), R21 and R31 represent an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituen_ -COOR5 (where R51 is an alkyl group having 1 to 10 ca_bon atoms); -OR61 (where R51 is an acyl group hav ng 2 to 7 carbon atoms; a tri(Cl - C7)hydrocarbcnsil-~ g_oup; 2 group which rorms an 2cetal _ond together with the oxygen atom to which R is ~cnded; an aromatic hydrocarbon group whic~ may ~e subst1tuted with a h210sen atom, a tri(C1 - C7)h;drocarbonsilyLoxy group, an acyloxy group having 2 to , carbon atoms, an zcyl group having 2 to 7 czrbon at_ms, an zlkoxyczrbonyl group having 2 to 5 carbon atoms, an alkyl group ha~ing 1 to 4 carbon atoms, and an 2;Xoxy group h2vins 1 to 4 carbon atoms); an aromztic hycrocarbon group which may be su~stituted with a halogen atom, a tri(C1 - C7)hydrocarbonsilylcxy group, an acyloxy group having 2 to 7 carbon atoms, ar. acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkyl-group h2ving 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 czrbon atoms, a 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 (IV-a-2), specific examples of R21 and R31 include the same specific examples as mentioned above for R2 and R3 in the abo~e formula (I).
In the above formula (V), Rl represents a substi-tuted or non-substituted hydrocarbon group having 1 to 10 carbon atoms, specific examples of Rl 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 presence of a basic com~ound, alumina or silica gel, and then the reaction product is subjected to oxidation reaction, deprotection reaction and/or protection - 42 - l 3 3 5 5 9 9 -reaction, if desired, whereby the 2-subs~ituted-2-cyclopentenones represented by the above formula (I-z-1) and (I-b-12) can be obtained. Such production processes can be accomplished by the same processes for producing 2-substituted-2-cyclopentenones represented by the zbove formul2 (I-b-11) from the 2,3-epoxycycIopentenones 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 1~ formula (I), the 2-substituted-2-cyclopentenones represented by the following formula (I-b-2):

O OH

R1 S ~ ~ R2 .... (I-b-2) ()n ~ R34 OR
2~ wherein Rl, 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 represent~d ~y the following formula (III-b):
o Il ~
~ . ... (III-b) \\R31 OR o wherein R31 represents an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may be as the substituent -CooR51 (where R5l 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 _ 43 _ 1 3 3 5 S 9 9 - 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 lS 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; 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 following formula (IV-b-l):
O

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

` - ~

Rl-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-S J~, .... (I-c-l!
~
R
~o~4o 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 er se, and may be prepared by the method described in Japanese Un~r;ned 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(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, an acyloxy group having 2 to 7 carbon -atoms, an acyl croup having 2 to , c2rbon atoms, an alkoxycarbonyl ~roup having 2 to _ carbcn atoms, an alkyl g-oup hav ng 1 to 4 carbon 2 _^ms, and an alkoxy group havlng 1 to ~ carbon atoms); 2n arom2tic hydrocarbon s.o~p which may be suks~iLuted with 2 halogen atom, a ~ri(Cl - C7)hydroc~-~onsilyloxy sroup, an acyloxy grou? having 2 to 7 ca~_cn atoms, an acyl group having 2 to 7 carbon atoms, 2n 21koxycarbonyl group having 2 to 5 carbon atoms, 2n 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 grcup, an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an-alkoxycarbonyl group hzving 2 to 5 carbon atoms, an alkyl group havins 1 to 4 carbon atoms and an al~oxy group having 1 to 4 c_rbon atoms.
Specific examples of R31 include th~ same specific examples as mentioned abo~e for R3 in the above formula (I). In the above formula (III-b), R40 represents a hydrogen atom or a prc~ected group of the protected hydroxyl group. Specific examples of R40 include a hydrogen atom; alkyl groups such as methyl, ethyl, propyl, and isopropyI; tri(C1 - 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-ethcxyethyl, 2-methoxyethoxymethyl, and tetrahyd-opyran-2-yl; and acyl groups such as acetyl, propion~-l znd butvrYl.

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-epoxycycloper.~anones represented - 1 3355~9 a, by the above formula (IV-a-1) bv subjecting the 2-cyclopen~nones representeà by the zbove formul2 (III-a) to euoxydization re2ction.
The 2,3-epoxycyclopentanones r-~resented by the above formu12 (Iv-~-l) obtained in the above epoxy-diz2tion ~eaction are novel compouncs. The reaction between the compounds of the abcve 'or~ul2 (I-~-b-1) znc the thiols represented by the above 'ormula (V) is carried out in the presence of a basic compound, alumina or silica gel.
In the above formula (V), R1 re?resents a substi-tuted or non-substituted hydrocarbon group having 1 to lO carbon atoms. Specific examples of Rl include the - same specific examples as mentioned above for tne 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-l), 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-1) 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 th~ above formula (I-c-l), R 1 represents a protected group of the protected hydroxyl group. Specific examples of R41 include alkyl groups such as methyl, ethyl, propyl, and isopropyl; tri(Cl - C7)hydrocarbonsilyl groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, _ 47 - 1335599 -t-~utyldiphenylsllyl, and ~_ benzylsilvl; g-oups which form an acetal bond t_gether wi.h the oxygen atom to whicn R~l is bonde~ such 25 mei_hoxymethyl, 1-ethoxyethyl, 2-methoxyet.~_xymethyl, a.-.d tetrzhyc_opyran-2-yl; 2nd 2cyl srou?s such as acetyl, pro~ionyl, and bu~y~il.

The compounds represented by the above formula (I-c-l) and the aldehydes represen~ed by the above formula (II
are subjected to aldol condensation reaction.
In the above formula (II), R represents an aliphatic hydrocarbon grou~ having 1 to 10 carbon atoms which may have as the substituent -COOR;1 (where R51 is an alkyl group having 1 to 10 carbon atoms); -OR61 lS (where R51 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 sroup 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 S
carbon atoms, an alkyl grou? 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(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 S
carbon atoms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.

Specific ex2mples of R ~ i^clude the same speci_-c ex2mples as ment-oned above ,or R2 in the above Lormulz (I).

The compounds represented by the above formula (I-c-l) and the 21dehydes represent~d by the above fo~ul2 (II) are subjectec to aldol cordensation reaction.
The alcol condensa_ior. -eaction is carried out in the presence of 2 b2_ic compound in a solvent.
Examples of the basic compound and the re2ction solvent include those described in: A. T. Nielsen, W. J.
Haulihan, Organic Reaction (Org. Rezct.), 16, 1 (1968);
H. O. House, "Modern Synthet-c Reactions" 2nd Ed., Benjamin (1972), p. 629; and ~ew Experimental Chemistry Course 14, II736, III851, etc.
For the aldol condensa~ion reaction, preferably metal amides such as lithium diisopropylamide, lithium diethylamide, and lithium bistrimethylsilylamlde; or dialkylborontrifluoromethanesulfonic acids such as dibutylborontrifluoromethanesulfonic acid in the presence of 2 tertiary amine such as triethylamine, diisopropylethylamine, and tributylamine, are employed.
When the aldol condensztion reaction is carried out by using a metal amide, pref2rably the amount thereof is 2S 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 rezction solvent, for example, ethers such as ether and tetrahydrofuran; and hydro-carbons such 25 petroleum ether, hexane, and pentane, may be employed. Preferably the reaction temperature is from -150C to 100C, more preferably from -80C to 0C.
When the aldol condensation reaction is carried out by using a tertiary amine anc a dialkylboryl trifluoro-methanesulfonate, preferably the amounts used thereof are, for example, 0.5 to 50 eauivalents, more preferably 1 to 10 equiv21ents, relative to the compound of the above formula (I-c-1).

_ 49 -The aldehyde of the ~ormula (II), -w;~ich is ..ne other starting mat~rial, ?referably is ~sed at a r~ti~
of 0.5 to 10 eauivalents, more prefe-abl-~ 0.8 to 2 equivalents, relative to the compound OL- the formula (I-c-l).
The react-on time depends on the s~--ting COmDOunc.
the reagents, and the re2ction solvent em loyed, but preferably is from 5 minutes to 48 hours, more preferably from lO minu~es to 12 hours.
After completion of the reaction, t.~ 2-substi-tuted-2-cyclopentenones represented by the following formula (I-b-20):
OH

R1-5 - ~ ~ R~ 20) oR41 ~herein R1 R21 R31 and R41 are as defined above can be obtained by isolating and purifying the reaction mixture by a conventional means such as ex~raction, water washing, drying, and chromatography, but the unpuri~ied 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 above 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-cyclope~tenones represented by the above formula (I-b-ll) from the 2-subs~ituted-2-cyclopentenones represented by the above formula (I-b-10).
Of the 2-substituted-2-cyclopentenones of the above formula (I), the 2-substituted-_ 50 _ 1 3 3 5 5 9 9 2-cyclopentenones represented by the following formula (I-a-2):
o R1 S ~ ~ R2 .... (I-a-2) ()n~R34 OR

wherein R , R R , R , 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): -OH

R1 S ~ R21 .... (I-b-20) oR41 wherein Rl 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), Rl 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 R31 represent an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -COORS
(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(Cl - C7)hydrocarbonsilyl group; a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aromatic Sl - 1 335599 hyGroczrbcn gr_u? which may be subslitu-ed ~L~ a halogen atom, 2 tri(C1 - C7)hydroca-bGr.ailylcx-i g-ou-, an acyloxy g~ou~ ha~ing 2 to 7 carbon a~^ms, 2n acyl s-oup havinc , _o 7 carbon atoms, an 21koxycz~bonyl grsup having 2 _o 5 carbon atoms, an al.'~yl g-^-p ha~ing 1 to 4 c~_bon atoms, ana an alko.Yy gro~?
having 1 to 4 ca-bon atoms); an arom2tic hyd~oc2rbcn group which m2 i be substituted with a halogen 2tom, a tri(C1 - C7)hydrocarbonsilyloxy group, an acy oxy group having 2 to 7 c2_bon atoms, an acyl group hav ng 2 to 7 carbon atoms, an alkoxyc2rbonyl group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an zlkoxy 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, 2n acyl group having 2 to 7 carbon atoms, an alkoxyca_bonyl group having 2 to 5 carbon atoms, an alkyl grG~p having 1 to 4 carbon 2 ~oms, or an alkoxy group havinc 1 to 4 carbon atoms. Specific examples of R21 and R31 in the above formula (I-b-20) include the same speci~lc examples as mentioned above for R and R3, respectively for the above ~ormula (I).
In the above formula (I-b-20), R41 represents a protected group of the protected hydroxyl grouD.
Specific examples of R41 include alkyl groups such as methyl, ethyl, propyl, and isopropyl; tri(Cl - C7)-hydrocarbonsilyl groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldl~henyl-silyl, and tribenzylsilyl; groups which form zn 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 butyryl.

The compound of the above formula (I-b-20) is subjected to dehydration reaction. This dehydration reaction can be carried out by the same method as used in the ~rep2-ration of the 2-subs~i_uted-2-cyclopentenones represented by the abo-.e fornul~ (I-b-10) from the 2-substituted-2-cyclopentenones represented by the above S formula (I-b-10), wnereby 2-subs~ituted-2-cyclopente-nones represented by t.~e followins formula (I-a-20):
o ~ r (I-a-20) ~ ~ R31 oR4 1 i Rl R21 R31 R41 and the representation are as defined above can be obtained.
The compound of 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 andtor 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-11) from the 2-substituted-2-cyclopentenones represented by the above formula (I-b-10).

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

~ a-3') -wherein R1, R2, n and the represent2tion ~ are as defined above; 2nc R33 represents a hydrogen atom or an aliphatic hydroca=bon a-cup having 1 to 9 carbon atoms havir.g as the subs~ituen~ -CooR5 (-~here R5 ~epresents hydrogen atom, an alkyl c~oup having 1 to 10 carbon atoms or one equivalen~ ca_ion); _oR6 (whe~e R6 is an acyl group having ~ to 7 c2rbon 2toms; a trl(Cl - C7)-hydrocarbonsilyl group; 2 group which for~s 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 h2ving 2 to 7 carbon atoms, an - acyl group having 2 to 7 carbon atoms, an 21koxycarbonyl lS group having 2 to 5 carbon atoms, an alkyl group having 1 to 4 carbon atoms, znd an alkoxy group hzving 1 to 4 car~on atoms); an aromatic hydrocarbon group which may be substituted with a halogen atom, a hydroxyl group, a tri(C1 - C7)hydrocarbonsilyloxy group, a c2rboxyl group, 2~ an acyloxy group having 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group having 2 to S carbon atoms, an alkyl group having - 1 to 4 carbon atoms, and zn alkoxy group h2ving 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 h2ving 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group h2vins 2 to 5 carbon 2toms, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; c2n be prepared by subjecting the 2-substituted-2-cyclopentenones represented by the formula (I-a-21):

_ 54 - l 3 3 5 5 9 9 o Il .
Rl_s ~ ~R21 .... (I-a-21) ()n ~ ~ R32 OR

1 R21 R4 n and the representa are as defined above; and R32 represents a hydrogen atom OL
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 R51 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 l 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 1 to 4 carbon atoms; and subsequently subjecting the reaction product to an oxidation reaction, deprotection reaction and/or - Ss - 1 3 3 5 5 9 9 protection reaction, if desired.
In the above formula (I-a-21), R is substituted or non-substituted hydrocarbon group having 1 to 10 carbon atoms, and specific examples of R include the same specific examples as mentioned above for the above formula (I).
In the above formula (I-a-21), R is an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -COOR5l l~ (where R51 is an alkyl group having 1 to 10 carbon atoms); -OR6l (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, 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 2~ 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(Cl - 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 R1 in the above formula (I).
In the above formula (I-a-21), R32 represents a hydrogen atom or an aliphatic hydrocarbon group having 1 - 56 - l 3 3 5 5 9 9 -to 9 carbon atoms which may have as the substituent -CooR5l (where R51 is an alkyl group having l to 10 carbon atoms); -OR5l (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 ato~ to which R51 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 acvloxy 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 ln 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 ~ t335599 methox-~me hyl, i-ethoxyethyl, 2-..__hoxye_hox~methyl, ~-~tetrahyd-opyran-2-yl and acyl sro~?S such 2S acetyl, propionyl, and butylyl.
The 2-substituted-2-cyclopentenones represented by the above fornula (I-a-21) can be prepared by forming an alkyldiene group 2t the 4-positior. of the cyclopen _~one skeleton by 2n elimination rezction, carrying cui ~he oxidation reaction when S bonded at the 2--os-tion is to be converted to sulfoxide or sulfon^, and further, subjecting the reaction product ~ a deprotection reaction of a hydroxyl group or c2-~oxyl group, and/or a protection reaction.
The compound of the above formula (I-a-21) is subjected to an elimination reaction, which is preferably practiced by using an acidic compound. As _h~ acidic compound, there may be employed organic c~-~cxylic acids such 2S
acetic acid, propanoic acid, but_-.cic acid, oxalic acid, malonic acid, tartaric acid, anc benzoic acid; inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and hydrofluoric acid; orsanic sulfonic acids such as p-toluenesulfonic acid, methanesulfonic acid, and benzenesulfonic acid, but prefera~ly, 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, dimethylformamide, and dimethylsulfoxide; halogenated hydrocarbons such as dichloromethane and chloroform; and acetonitrile and nitromethane,-whlch 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 equiv~lents per 1 mol of the compound of the above formula (I---21).
Preferably, the amount of thC solvent used is 1 to 5 ~ 1 3 3 5 5 9 9 lOCO-'_ld vol~e, more prefe-ably S to iOO- old ~olum~, relzt ~re to the compounà repres2nted by the aDove fo~mula (I-a-21). The reaction temper2-ure may dl fe~
de?e-.ring on the sta-ting compound, the acidic compound, anc t:~e amount of solvent employed, but prc'e-ably is frcm -20C to 100C, more preferably frcm O~C to 50C.
The r~~ction time, which is differs depenGing on the conditions, is about 0.1 to 100 hours. The progress o-the reaction is monitored by a methoà such as 1~ chromatography.
After completion of the reaction, the desiredcompound may be purified by a conventional means such 2S
extraction, washing, concentration, and chromatography, or combination therecf, but the unpurified reaction mixture can be subjected as such, without isolation of the desired c2mpound, to an oxidation reaction, deprotection reaction or protection reaction, if desired, to prepare the 2-substituted-2-cyclopentenones represented by the above formula (I-a-3). 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-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'):

B Al1 R -S ~ R2 .... (I-2) ()k~R3 - ~9 - 1 3 3 5 5 9 9 -wherein R1, R2, R3 and X are as àefined above;
A11 and B are such that A11 represen~s 2 group or ( ~
-S-R
and B represents a hydrogen atom or A11 and B together represent a single bond: ~ is 1 or 2; and i is 0, 1, or 2, can be prepared by subjecting the 2-substituted-2-cyclopentenones re1~ the following formula (I-1):

R -S ~ ~ R21 .... (I-1) (O)R ~ 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 hydrog~n atom or A12 and B
together represent a single bond; and R~0 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, 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 0, 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 (o) .
1~ ]1 -S-R , or A12 and B are mutually bonded together to represent one bonding arm. Specific examplQs of A12 and B include the same specific examples as mentioned above for the above formula (I).
In the above formula tI-1), R1 represents a substituted or non-substituted hycrocarbon 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), ~ 1 represents an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituer.t -CooR51 (where R5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or one equivalent cation); _oR6 (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 2~ 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 - 35 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, 2n alkyl sroup having 1 to 4 c2rbon 2te.~.-and an alkoxy gro~p having 1 to 4 carbon atoms.
Specific exzmples of R21 include the s2me specific examples as mentioned above for R2 in the above S formula (I)-In the 2bove formula (I-1), R30 represents a substituted or non-substituted aliphatic hydrocarbon group having 1 to 10 carbon atoms. Where R30 is a single bond znd bonded to the cyclopentene skeleton, X~
represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group, and when R30 is a double bcr.^
and bonded to the cyclopentene skeleton, XO represents a bond in S2iC double bond. Specific examples of R30 an~
XO include the same specific examples as mentioned abc-.re lS for R and X, respectively, in the above formul2 (I).
In the above formula (I~ represents O or 1 crd 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~ (I-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-substitutec-2-cyclopentenones represented by the above formula (I-b-11) from the 2-substituted-2-cyclopentenones represented by the above formula (I-b-10).
The preparation processes according to the embodi-ments as shown below are applicable.

1. A process for preparing the 2-substituted-2-cyclopentenones represented by the following formul2 (I-b-ll):

O OH
R1-S ~ R2 .... (I-b-11) ~ / R34 wherein R1 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 R is bonded; an aromatic hydrocarbon group which may be also 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); 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 - ~ 3 3 S S ~9 comprises subjecting the 2-cyclopentenones represented by the following formula (III-a):
O OH

~]l .... (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); -OR51 (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 R51 is bonded; an aromatic hydrocarbon group may be also 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 S carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms3; 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 S carbon atoms, an : alkyl group having 1 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(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; to an epoxydization reaction to obtain the 2,3-epoxycyclo-pentanones of the following formula (IV-a-l):

O OH

~,~J~R21 ~ .... (IV-a-1) wherein R21 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 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-1):
o Rl_s ~ ~ ~R2 .... (I-a-l) Il '~ -()n \ R34 wherein Rl, R2, R34, and n are as defined above; and therepresentation ~r~v~ 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 which comprises dehydrating the 2-substituted-2-cyclo-pentenones represented by the following formula (I-b-10):

OH

\ 3l .... (I-b-10) wherein Rl R21 and R31 are as defined abo e 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-l) ()n \ R34 wherein Rl, R , R , n and the representation ~_v are as defined above, and the 2-substituted-2-cyclopentenones represented by the following formula (I-b-12):
()m O S-R

Rl_s ~ ~ R --- (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):

o 1 335599 J~
~ ~R21 / ~ / .... (IV-a-2) O ~ \ 31 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

Rl- ISl R2 .... (I-b-2) ()n ~ R34 \

oR4 wherein Rl, 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 .... (III-b) ~` R31 oR40 where n R31 represents an aliphatic hydrocarbon group having 1 to 10 carbon atoms which may have as the substituent -CooR51 (where RS1 is an alkyl group having 1 to 10 carbon atoms); -OR61 (where R6 is an acyl group having 2 to 7 carbon atoms; a tri(C1 - C7)hydro-carbc~silyl group; a group which forms an acetal bond together with the oxygen atom to which R61 is bonded; an aroma~ic 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; 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-l) O ~ ~ R31 --- (IV-b-l) oR40 -wherein R31 and R40 are as defined above, then reacting the thiols represented by the following formula (V):
R -SH .... (V) wherein Rl 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 (I-c-l):
o R1 S ~ .... (I-c-l) \\ R31 oR41 wherein R1 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 subsequently, 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 Il Rl_s ~ R2 .... (I-a-2) ()n ~ R34 OR

_ - 69 - 1 3 3 5 5~ 9 wherein R , R , R3 , R , n and the represen~ztion are as defined above, which comprises dehydrating the 2-substituted-2-cyclopentenones represented by the following formula (I-b-20):
O OH

Rl_s ~ ~ R2i --- (I-b-20) \ R3 oR41 wherein Rl 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_s ~ ~R2 .... (I-a-3') ()n ~ R33 wherein Rl, 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 3~ 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(C1 - C7)hydrocarbonsilyloxy group, a carboxyl group, an acyloxy group having 2 to 7 carbon atoms, an acyl - 70 - 1 3 3 5 ~ 9~
-group having 2 to 7 carbon atoms, an alkoxycarbonyl group havins 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(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; 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; which comprises subjecting the 2-substituted-2-cyclopentenones represented by the formula (I-a-21):
o Rl-S - ~ R21 .... (I-a-21) ()n 4 R

OR

1 R21 R4 n and the representa are as defined above; and R32 represents a hydrogen atom or 3~ an aliphatic hydrocarbon group having 1 to 9 carbon atoms which may have as the substituent -COORSl (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 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 S
carbon atoms, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group havin~ 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 ~roup, 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 - C7jhydro-carboncilyloxy group, a carboxyl group, an acyloxy grouphaving 2 to 7 carbon atoms, an acyl group having 2 to 7 carbon atoms, an alkoxycarbonyl group ha~ing 2 to 5 carbon atoms, an alkyl group having l to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms, and subsequently subjectins 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) 11 B A

Rl-S ~ \ R2 .... (I-2) ()k ~ ~3 wherein Rl, R2, R3 and X are as defined abo~e; A11 and B
are such that Al1 represents a hydroxyl group or ()il -S-R

and B represents a hydrogen atom or A11 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-1):
B A
R1-S ~ ~ \ R21 .... (I-l) ()Q ~ R30 XO

wherein R1 and R21 are as defined above; A12 and B are such that A12 represents a hydroxyl group or -S -Rl and B represents a hydrogen atom or A12 and B together represent a single bond, and R30 represents a 2^ 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, XO
represents a hydrogen atom, hydroxyl group or a protected hydroxyl group,~and when R30 is a double bond 2~ 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 - l 3 3 5 5 9 9 -wi~h 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 - 74 - 1 3 3 5 ~ 99 -hydrogen carbonate, sodium lauryl sulfate or stearic acid monoglyceride; humectants such as glycerine;
absorbers such as kaolin, and colloidal silica; and lubricants such as talc and granular boric acid may be 5 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 lS 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 mmedi2.ely before use.
The comDounds of -:~e pr_sent invention also can be used by Iormins inclus_~n comDounds toge,her with ~, 3 or -cyclodextrin or me_hvl2ted cyclodextrin, znd may be injectable preparatior.s in the li?ogenated form.
The ef'ective coc- of the compounds of the pres-nt invention depends on th3 2ge, sex, and conditicn of the Datient, but generally may be administ~red at 102 to 105 ~gl~g/day, prefera~ly 5 x 102 to 104 ~g/Kg/day.
The 2-substituted-2-cyclopentenones of the present invention have a poten_ growth inhibitory effect against L1210 leukemia cells even at a low concentration, are useful as antitumor age~ts.
Furthermore, the p-esent compounds have the activities of enhancinc 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 zccelerator, and are effective for the therapy or prophylaxis of osteopo-osis or osteomalacia.
Furthermore, the oresent compounds are expected to exhibit an antiviral ac~ivity 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 Svnthesis of 2,3-eooxy-5-(1-hydroxy-6-methoxy-carbonylhexyl~-4-(3-t-butyldimethvlsilyloxY-l-octenyl)-cvclopentanone O OH

\/ ` ~ \` COOCH3 osix O OH

~\/\/
osi ~

A solution of 3.30 g of 5~ 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.~8 ml of an aqueous lN sodium hydroxide were dropwise added thereto. After stirring at 0C for 3 hours, the re2ction mixture was extracted with an addition of ethyl acetate and saturated aqueous ammonium chloride, and the ext~act 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 give 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 CDCl3 ~
-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 obt2ined in the same manner as in Example 1.

U~ ~ ~ ~ o X ~ -- E _ -- ~ ~ ~ ~ o~

$ ~ ~ o ~ ~ ~ X
o ~ ~ ~ _ ~ _ ~ _ _ _ a .j _ U~

~ O ' E{ N ~ C ^ _ ~ ' O
e D~

0=~

X ~ Z

- 7~ -Z Q ~ ~ O ~ ~ r~ I _ o ~ _ ~ ~i _ ~ _ _. _ o -- o -- -- ~ -- k -- --.

o o~ ~ ~ 5 ~ , O ~ ~
, I

o~ X

X ~ Z

Table 1 ( Continued ) Exam- Starling compound 2,3-epc)xy Yif~ld NMR
ple 2-cy~lDpentanonescy~lDpentanones ( 96 ) ( ~ C D C13 ) No .

4 O OH O OH 43 1.1-2.7 (29H, m), " `\/~, C O O C I 13 ,~J~ c o o c ll 3 2 . 9-3 . 3 ( ] I ~, m ), 3 -\\1~ 0 \ ~0 (5H, m), 3-69 (3ll, s), - - 4.5-5.0 (2EI, m), 5.3-5.8O _~ 0~ (2H, m) 5- ( 1-hydroxy-6-methoxy- 2, 3-epoxy-5- ( 1-hyd~oxy- ~
carbonylhexyl) -4- [ 3- 6-methoxyrArbonyl- ~n (te~ahydlo~ldn-2- hexyl)-4-[3-(tetrahydro ~o y~Dxy ) -3-cyc~Lohexyl-l- pyran-2-yloxy ) -3-cyc~
propenyl] -2- hexyl-1-propenyl] cycLo cyclopentenone pentanone Table 1 ~ Continued ) Exam- Star~ng compound 2,3-epoxy Yi~Ld NMR
ple 2-cyc Lopentanonescyc~Lopentanones ( % ) ( ~ C D C13 No .

O OH O OH 69 0.7-1.1 (3H, m), 1.1-3.1 (9H, m), 3.3-3.6 O / (lH, m), 3.49 (lH, d, O J = 2.6 Hz), 3.76 (lH, d, J = 2.6 Hz), 4.3-4.7 5-(1-hydroxy-3-phenyl- 2,3-epoxy-5-(1-hydroxy- (lH, m), 6.4-6.8 2-propenyl)-4-butyl-2- 3-phenyl-2-propenyl) -4- ( lH, m ), 7 . 0-8 . O
cycLopentenone buty3~3r~opentanone (511, m) ~ 81 - I 335599 Exam~le 6 Svnthesis of 2-methYlthio-5-(1-hvdrox~-6-me~hoxy-carbonylhexyl~-4-f3-t-butvldimethYlsilYloxY-l-oc~2n~1) 2-cyclopentenone O OH
'I ~

v \~~~~ .
osi ., O OH
MeS ~ COOCH3 ~~
osiy 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-methoxycarbor.yl-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 W2S
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-(l-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyl-dimethylsilyloxy-l-octenyl)-2-cyclopentenone.
Spectrum data lH-NMR CDCl3 6 0.00 (3H, s), 0.03 (3H, s), 0.87 (9H, s), 0.7-1.1 (3H, brt), 1.1-2.3 (20H, m), 2.33 (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_5.5 (2H, m), 6.78 (lH, d, J = 3 Hz).
Exam~les 7 - 9 The 2-substituted-2-cyclopentenes listed in Tabie 2 were obtained in the same manner as in Example 6.

Table 2 Exam- 2-Substituted-2- Yi~Ld NMR
ple Starting compound -cyc~Lopentenones ( 96 ) ( ~C D C13 ) No .

7 O OH O OH 54 0.04(6H, s), 0.89 CoocH3 ~ -~/`COOCH3 (9H,s), 1.1-2.1 o~l~, ~) 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-(1-hydroxy- 2-methy~h~5-(1- (lH, m), 4.6-4.85 6-methoxycarbonyl-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 , dimethyl.~ilyloxy-3-cy~ ( 3-t-butyklimethyl- J = 3 . O Hz ) pentyl-l-propenyl) cy~ silyloxy-3-cy~opentyl-pentanone 1-propenyl)-2-cy~lD
pentenone 1 33~599 ~ -- o ' ` ~ ` a~ ~ co ~ C~ t` o ` D ~ I D D ~ ~ 11 _ -- ~; -- ` _ _ _ O

O O -- r~

,_ O ~ , E ~ ~
u~ e ~ ~ 4 ~

O ~ ~D r e ~L z ~_ 1 335599 , U~ ~
o _ ~ _ . .
:~ ~3 e ~. e ' ' Z ~ ~ ~ ~ ~ O

-~ e ~o e e O _ ~ _ _ _ a _ 9 " .~

~ ~ , I' i o ~ ~ ~
~ ~ Z

- 86 - 1 3 3 5~9 Example 10 SYnthesis of 2-(2,3-dihYdroxY~roPylthio~-5~
hydroxy-6-methoxycarbonyl-2-hexYnYl)-4-(3-t-butYl-dimethYlsilyloxy-3-cycloPentYl-l-~roPenyl)-2 Pentenone O OH

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 ~1 of triethylamine was added.
Then, 12 mg of 2,3-dihydroxypropanethiol W2S 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~ hydroxy-6-methoxy-carbonyl-2-hexynyl)-4-(3-t-butyldimethylsilyloxy-3-cycl-opentyl-l-propenyl)-2-cyclopentenone.
Spectrum data 0.05 (3H, s), 0.09 (3H, s), 0.8~ (9H, s), 1.1-2.0 (llH, m), 2.0-2.7 (5H, m), 2.7-3.4 ~ - 87 - l 3 3 5 5 9 9 (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.

T~ble 3 Ex-m- Se-rtlng compount 2-Sub~tltutsd-2-cyclo- Yl-ld NMR
No. 2,3-epoxycyclopent-nones Thlol~ pentenones ~ CDCI ) Il ~ C00C2 C93~oc~Vv S ~ ~ C00C9~ ~93, ), I 1-2 ;

0 CH 00C ~ ~ SH O ~17h, m), 2.1-3.1 OSi~c OSi,~ (IOH, m), 3.4-3.8 (lH, m), 3.67 (6~, g), 3.8-4.0 ~Ih, m), 4.6-4.85 oo 2,3-epoxy-5-(1-hydroxy-6- 5-methoxyc-rbonyl- 2-t5-methoxycarbonylpen- (lH, ~), 5.4-5.8 metboxyc-rbonyl-2-hexynyl)-4- pen~-ne-l-tblol tylthlo)-5-~1-hydroxy-6- ~2H, m), 6.92 ~IH, ~3-t-butyltlmethyl~llyloxy-3- methoxyc-rbonyl-2-hexynyl)-4- d, J - 3.2 Hz) cyclopentyl-l-propenyl)cyclo- (3-t-butyldlmethylsllylo~y-3- W
`pent-none cyclopentyl-l-prop~nyl)-2- ~1 cyclopentenone ~J' Table 3 ~Contlnued) f Exam- Startlng compound ple 2-Substltuted-2-cyclo- Yleld NMR
No. 2,3-epoxycyclopentanone~ Thlols pentenones (~) t~CDCl3) 12 OH 74 0.04 (6H, a), 0.90 O ¦ rCOOCH (9H, 9), 1.0-3.0 S~ ~ ~ S- ~ (23R, m), 3.35-3.7 OSl- (Ih, m), 3.68 (3H, a), 3.8-4.0 (IH, m), 4.6-4.8 (IU, m), 5.4-5 7 3-phenylpropan~-1- 2-(3-phenylpropyltbio)-5-(1- (211, m), 6.89 (IH, thlol hydroxy-6-me~hoxyc~rbonyl-2- d, J - 2.8 Hz), hexynyl)-4-(3-t-bu~yldlme~hyl- 7.0-7.4 (5H, m) sLlylaxy-3-cyclopentrl-1-proprnyl~-7-~pclop-ne-rloDe ~n T~ble 3 ~Coneinued) Ex-m- Se~relng compound 2-5ub~eltueed-2-cyclo- Yleld NMR
ple No. 2,3-epoxycrclopent~nones Thlols peneenones (2) (~CDC13) 13 0 OH 91 0.07 (6N, ~), 0.89 - ~ C OCH3 (9H, 9), 1.1-2.0 S~ ~ S ~ O ~lli3, m), 2.0-2.7 - ~5H, ~), 3.0-3.3 OSl,~ (IH, m), 3.4-3.6 (lH, m), 3.70 (3H, 8), 3.8-4.0 Th~ophenol 2-phenylthlo-5-(1-hydro~y-6- (IH, m), 4.7-4.9 meehox~curbonyl-2-hexynrl)-4- (IH, m), 5.4-5.8 (3-t-butyldlmethylsilyloxy-3- ~2il, m), 6.85 (IH, cyclopentyl-l-propenyl)-2- d, J - 2.7 Hz), cyclopeneenone 7.2-7.7 ~5il, m) W

W
~n ~O

T-ble 3 (Con~inu~d) -Ex~m- Se~r~ing eompount 2-Substltut-d-2-eyclo- Yleld NMR
pl-p-ne-non-s( ~ ) No. 2,3--poxyeyelop-nt-noneJ ThiolJ ~CDCl3) 14 SH OH 85 0.08 (6R, 9), 0.89 ~ O _ ~COOCH (9H, 9), 1.1-2.0 Co O S~ "o), ~ ~ ~ 2.0-2.7 (5H, ~), CH O OSi-~ 3.3-3.5 (IH, ~),3.69 (31~, 9)~
3.8-4.1 (2H, m), 6-m-thoxyn~phth-- 2-(6-m~thoxrn-phthyl-2-thio)- 3.97 (3H, 9)~ ~J
lene-2-thiol 5-(1-hydroxy-6-mothoxy- 4.6-4.8 (lH, ~), e-rbonyl-2-h-xyDyl)-4-(3-~- 5.4-5.8 (211, ~), bueyldlm-thylsilylo~y-3-cyclo- 6.74 (IH, d, p-ntyl-l-prop~nyl)-2-cyclo- J - 2.7 Hz), pent-none 7.0-8.1 (6H, ~) ~J~
.. ~n Table 3 (Conelnucd) Exam- Searein~ compound 2-Subaeleueed-2-cyclo- Yleld NMn ple No. 2,3--poxycyclopeDtanones Thiol~ penconones ~2) (~CDCl ) 0 08 OH 75 0.04 (3H, 8), 0.09 ~ ~ ~ COOC8 ¦ COOCH (3H, 8 ), 0.89 o ~ CH CH SH CH CH S ~ (9H, 8), 0.7-1.1 OSl ~ ~ (6H, m), 1.1-2.7 OSi ~ (22H, m), 3.1-3.3 (lH, m), 3.68 (311, 8~, 3.6-3.8 2,3-~poxy-5~ hydroxr-6- ehanethlol 2-ethyl~hio-5-~1-hydroxy-6- (IH, brs), 3.9-4.2 metboxycarbonylhexyl)-4-~3-e- methoxycarbonylhexyl)-4-~3-~- (IH, m), 5 3-5.7 hutyldlmethylsllyloxy-l- bu~yldlmeehyl9llyloxy-l- ~2H, m), 6.79 ~111, oceenyl)cyclopen~anone octenyl)-2-cyclopeneenone d, J - 2.9 H2) W
U~

-- g3 --~ 1 335599 o ~ ~ o o . . ,, . ~ o o O O : t~ t~l t'~ ~1 '~1 N 1~ 1 t '~ _ _ _ _ _ _ _ _ 3 a ~ a a I _ ~ N ~1 m 3 3 ~ 3 m "~

o ~ .

t~ <
o ~ o r 8 < .a I c t~
o t`l ( / t~7 .-- O t`l > <~ I I Y , -~
m ~ ~ _ ,, o ~ W
O =~ '- r t~

t,~ t~
-~
~ ~ _ E~ q O ~ ~

~ .

t ~ r 8 > ~ _ < ~
o / ,~ / IA . ~ I r t~ O '~<~
O t~

~ _I O ~
K O. z _.

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Ex~m^ St~rtln~ compound 2-Sub~tl~uted-2-cyclo- Yl-ld NMR
pl.
No. 2,3-epoxycrclopent-none- Tblol~ pentenonee ~2~ ~CDCl3) 17 0 08 0 OH 57 0.7-1.1 (3H, m), COOCd ~ ~ COOCd~ 2.7 (3Id, ~1, _ 3 2 CH3CR2S ~ ~ 3.0-3.3 ~111, m), O ~ ~ i.69 (3~
O ~ 3.3-4.3 (311, ~), 4.5-5.0 (2H, m), 5.3-5.7 (2~
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~ 1 335599 Exam~le 13 Svntheses c 5-(6-methoxJcarbonvl-1-methvl-hio-hexvl)-2-methvl sio-4-(l-octenyL~-2-cvclo~ente~one ar,d 5-'6-methoxYca__cnYlhexYlidene)-2-meth~lthio-A-(1-oc-enYl)-2-c-~cl_~entenone C

~ ~ ,~COOCH3 O \
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CH3S ~ ~ ~ COOCH~
~ \l \~\/\
(A) CH3S ~ ~ ~ COOCH3 (B) To a soluticn 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-(1-octenyl)-5-(6-methoxyczrbonyl-hexylidene)cyclopentanone in 1 ml of methanol W2S added, then triethylamine (1~4 ~l) was added, and the mixture was stirred at 0C for 4 hours. The reaction mixture W2S diluted with saturated aqueous ammonium chloride and ex~racted with ethyl acetate. The organic layer was washed with saturzted aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, concentrated and then pro~ide~ for silica gel column chromztogrzphy to give 16.7 mg (yield 20%) of 5-(6-methoxycarbonyl-l-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-- g7 _ 1 33 5 5 99 ~, ' pentenone.
Spectrum data (A) lH-NMR (CDC13) 0.89 (3H, brt, J = 5.5 Hz), 1.0-2.5 (20~, m), 2.37 (3H, s), 3.68 (3H, s), 3.96 (lH, b~d, - J = 4.0 Hz3, 4.20 (lH, dd, J = 15.0, 8.5 Hz), 4.67 (lH, dt, J = 15.0, 6.4 Hz), 6.5-6.8 (2~, m)-(B) 1H-NMR (CDC13) D.8~ (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)r 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).
Exam~le 20 Svnthesis of 2-methylthio-5-(1-hvdroxy-6-methoxy-carbonvlhexyll-4-(3-hvdroxv-1-octenvl)-2-cyclo~entenone O OH
MeS ~ ,_~/ COOCH3 OSi x O OH
MeS ~ ~ ~COOC~3 OH
To 350 mg of 2-methylthio-5-(1-hydroxy-6-methoxy-carbonylhexyl)-4-(3-t-butyldimethylsilyloxy-1-octenyl)-2-cyclopentenone obta-ined 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 - t 3 3 5 5 9 9 stirred for 24 hours. Toluene was then added, anc after concentration, the concentrate was diluted with saturated aqueous sodium hydrogencarbonate and ex~-acted with ethyl acetate. Subsequently, the extract was washed with saturated aqueous sodium chloride, dr ed over anhydrous magnesium sulfate, filtered and cor.cen-trated, followed by silica gel chromatography to g ve 178 mg (yield 65%) of 2-methylthio-5-(1-methoxyca~onyl-hexyl)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.
Spectrum data lH-NMR CDCl3 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.a (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 MeS ~ y ~ COOCH3 \\ I
'~1 --OH

O O OH
Il il I
MeS ~ COOCH3 ~\/
OH
To a solution of 35 mg of 2-methylthio-5-(l-hydroxy-6-methoxycarbonylhexyl)-4-(3-hydroxy-l-octenyl) 2-cyclopentenone obtained in Example 20 dissolved in 5 ml of dichloromethane was added 17 mg of 3-chloro~er-~, .
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-1-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 (lHj 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-l-octenyl)-2-cyclopentenone O OH
MeS ~ COOCH3 ~ /
osi x O
MeS ~ ~ COOCH3 ~\~' osi ,~
To a solution of 3.47 g of 2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-(3-t-butyldimethyl-silyloxy-l-octenyl)-2-cyclopentenone obtained in Example 6 in dichloromethane (30 ml) was added dimethyl-loo - 1 335599 ~, aminopyridine (1.54 g) and the mixture was cooled to 0C. 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 S were added ethyl acetate and an aqueous potassium hydrogensulfate, and the product was extracted into an organic layer. The extract was washed with saturated aqueous 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 lH-NMR CDCl3 0.00 (3H, S)r 0.02 (3H, s), 0.87 (9H, s), 0.7-1.1 (3H, brt), 1.1-2.3 (18H, mj, 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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1 ~35599 Exam~le 34 Svnthesis of 2-methylthio-5-~6-methoxvcarbonyl-hexvlidene)-4-(3-hYdroxy-l-octenyl)-2-cyclopentenone O

MeS ~ COOCH3 I

osi X

MeS ~ COOCH3 '~ ~1 \'\' OH
An amount of 1.42 g of 2-methylthio-5-(6-methoxy-carbonylhexylidene-4-(3-t-butyldimethylsilyloxy-1-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-~ CDC13 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 3 3 5 5 9 9 ExamDles 35 - 44 2-Substituted-2-cyclopentenones listed in Table 5 were obtained in the same manner as in Example 34.

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- 123 ~ 1 3 3 5 S 9 9 Example 45 SYnthesis of 2-methylthio-5-(6-carboxYhexYlidene)-4-(3-hYdroxyl-octenyl)-2-cyclopentenone MeS ~ ~ COOCH3 ~\~

OH
o MeS ~ ~ COOH

OH

To a solution of 345 mg of 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-1-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 d~ied over anhydrous magnesium sulfate, filtered and concentrated, followed by silica gel chromatography to gi~e 193 mg (yield 58%) of 2-methylthio-5-~6-carboxyhexylidene)-4-(3-hydroxy-1-octenyl)-2-cyclopentenone.
Spectrum data lH-NMR CDC13 0.86 (3H, brt, J = 5.6 Hz), 1.1-2.5 (20H, m), 2.34 (3H, s), 3.9-4.2 (2H, m), 5.2-5.g (2H, m), 6.6-6.8 (2H, m).
Example 46 SYnthesis of 2-methylsulfinyl-5-t6-methoxycarbonvl-hexylidene)-4-(3-hydroxy-1-octen~l)-2-cYclo~entenone MeS ~ ~ ~ ~ COOCH3 ~,, I

OH

O O
MeS ~ ~ COOCH3 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 - l 3 3 5 5 9 9 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 H-NMR CDCl3 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-t3-hYdrox~-1-octenYl)-2-cyclopentenone o ~IeS ~ ~ COOCH3 ~

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 obtained 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 - l 335 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-methYlsulfinYl-5-(6-methoxYcarbonyl-hexylidene~-4-(3-hydroxy-1-octenyl)-2-cYclopentenone o MeS ~ ~" COOCH3 OH

O O
MeS ~ COOCH3 OH

To a solution of 17.6 mg of 2-methylthio-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone obtained in Example 34 in methanol (0.5 ml) was added a solution of 2KH505.KHS04-K2S04 (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 suIfate and filtered, followed by concen-~ - 127 - l 335599 -tration. The concentrate was subjected to silic2 5el chromatography to obtain 3 mg (yield 16%) of 2-methyl-sulfinyl-5-(6-methoxycarbonylhexylidene)-4-(3-hydroxy-l-octenyl)-2-cyclopentenone.
Example 49 Svnthesis of 2-methylsulfonyl-5-(6-methoxYcarbonvl-hexylidene)-4-(3-hydroxy-1-octenYl)-2-cyclopentenone MeS ~ ~ /COOCH3 `~ '\/
I

OH

O O
MeS ~ ~/'\ , COOCH3 Il \\ /
O ~j~~ ' .

~H

A solution of 18 mg of 2-methylthio-5-(6-methoxy-~5 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 (l 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 128 ~ 33~-~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 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 ~ ^~ / COOC~3 O O
MeS ~ COOCH3 ,~

A solution of 9 mg of 5-(6-methoxycarbonylhexyli-dene)-2-methylthio-4-(1-octenyl)-2-cyclopentenone obtained in Example 19 dissolved in 2 ml of methanol, and S00 ~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 ~ - 129 - l 3 3 5 5 9 9 subjected to silica gel column chromatog-_?hy to give 4.3 mg (yield 48~) of a mixture of isome-s of 5-(6-methoxycarbonylhexylidene)-2-methylsulfir.~-1-4-(1-octenyl)-2-cyclopentenone.
Spectrum data lH-NMR (CDC13) -0.88 (3H, brt, J = 6.0 Hz), l.C-2.5 (20H, m), 2.86 and 2.88 (3H, s), 3.67 (3:~., 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) Exam~le 51 Syntheses of 2,3-ePoxy-4-trimethylsllyloxY-4-(4-phenoxybutyl)cYclopentanone and 2,3-epoxv-4-hydroxy-4-(4-phenoxybutyl)cYclo~entanone O O

OPh O OPh OSiMe3 OSl~Ie3 - (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. ~n amount of 390 ~l of lN aqueous sodium hydroxide was added, and the mixture was stirred for 2 hours. Then sa.urated aqueous ammonium chloride was added, and the mixt~re was extracted with ethyl acetate. The organic 12yer ~-- 5 washed with saturated aqueous sodium chloride and ~ried over anhydrous magnesium sulfate. After filtraticr. and concentration, the concentrate was subjected to Si'! i ca gel column chromatography to give 892 mg (yield 3A ~ ~ of 2,3-epoxy-4-trimethylsilyloxy-4-(4-phenoxybutyl)cy^lo-pentanone and 1.38 g (yield 53~) of 2,3-epoxy-4-hy~-oxy-4-~4-phenoxybutyl)cyclopentanone.
Spectrum data (C) H-NMR (CDC13) 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-butyl)-2-cYclopentenone - O O

~eS

OSiMe3 OH

To a solution of 25 mg of sodium thiomethoxide dissolved in methanol, 51 ~1 of acetic acid was adcad, and the mixture was stirred for 10 minutes. Triethyl-amine (170 ~1) was then added, and after the mixture was - stirred for 10 minutes, a solution of 16 mg of 2,3-- 131 - l 335599 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 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 sodium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromatography to obtain 7.1 mg (yield 51~) of 2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone.
Spectrum data H-NMR (CDCl3) 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-but~l)-2-cyclopentenone O O

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 - 132 - l 335599 - saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to sili-~
gel column chromatography to give 1.39 g (yield 83~) o_ 2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclo-pentenone.
Exam~le 54 SYnthesis of 2-methylthio-4-~4-phenoxvbutyl)-4-trimethylsilyloxY-2-cyclopentenone O O

OPh ~ OFh OH OSi ~
To a solution of 400 mg of 2-methylthio-4-hydroxy-4-(4-phenoxybutyl)-2-cyclopentenone obtained in Example 5Z or Example 53 dissolved in 4 ml of dimethyl-formamide were added 279 mg of imidazole and 260 ~l 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 wate-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-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone.
Spectrum data H-NMR (CDCl3) 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-silyloxy-2-cyclopentenone - o o s =

\/\~\~
osi _ osi-- -To a solution of 3.3 g of 4-octyl-4-trimethylsily-loxy-2-cyclopentenone dissolved in 50 ml of methanol was 1~ added, under ice-cooling and stirring, 5.0 ml of an aqueous 30% hydrogen peroxide, znd 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 laye_ 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.
A solution of 910 mg of sodium thiomethoxide dissolved in 100 ml of methanol was stirred under ice-cooling and stirring for 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. ~fter 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. ~he organic 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

1 335~9 .
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 3 0.06 (9H, s), 0.89 (3H, brt), l.1-l.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 _ l 335599 Example 61 SYnthesis of 2-phenYlthio-4-trimeth~lsilyloxy-4-(4-~henoxYlbutYl)-2-cyclopen enone o O ~ o OH

~~ {~
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 by adding 1.0 mI of triethylamine. Then, 7g0 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 S 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 - 1 3~ 5 5 ~9 ~, 2-phenylthio-4-timethylsilyloxy-4-(4-phenoxylbutyl)-2-cyclopentenone was obtained.
Spectrum data lH-NMR CDC13 ~
0.05 (9H, S), 1.1-1.9 (6H, m), 2.63 (2H, S), 3.95 (2H, t, J = 6.0 Hz), 6.8-7.7 (llH, m) Example 62 Synthesis of 5-~4,7-bis(t-butyldimethylsilylox~-1-hydroxy-2-hePtenyll-2-methylthio-4-(4-phenoxybutyl~-4-trimethylsilyloxy-2-cyclopentenone o J, MeS i\
OPh OSiMe O OH OSi~

MeS ~ OSi~
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 - ~335599 washed with saturated aqueous sodium chloride and c_ie~
over anhydrous magnesium sulfate. After filtratio~ 2nd concentration, the concentrate was subjected to sil C2 gel column chromatography to give 1.81 g (yield 75~) of a mixture of isomers of 5-[4,7-bis(t-butyldimethyl-silyloxy)-l-hydroxy-2-heptenyl]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone.
Spectrum data Less polar isomer lH-NMR CDC13 ~
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 H-NMR CDC13 ~
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).
Examples 63 - 71 2-Substituted-2-cyclopentenones listed in Table 7 were obtained in the same manner as in Example 62.

T8bl~ 7 Exsm- StsrtLn~ compound pLe 2-Sub~ltutdd-2- Yleld NMR
No. 2-5-baele-ced-2-cyclop-c~-Do=-J Aldebyd-- cyclopect--~ ACDC1 63 O O O Oh 65 0.07 (9H, ~), CR S ~ ~ ~ COOCR~ R ~ 1.1-2.R (22R, 1, O ~ CH S - ~ COOCH3 2.35 (311, 9), 3.67 - S10 ~ O { ~ (311, 8~, 3.8-4.3 S10 (3~ j, 6.7-7.5 (6H, m) 2-methylthlo-4-~4-phenoxy- 3-(4-matboxrcsr-bueyl)-4-crlmeehyl~llyloxy-2- bonyLcyclohuxyl)pro- 2-meehylthlo-5-[1-hydroxy-3-cyclop~n~enone pan~l (4-methoxycsrbonylcyclo-hexyl)propyll-4-(4-pb~noxy- ~J~
bu~yl)-4-erlme~hyl~llyl-2- ~Jl cyclopen~enone ~

Tuble 7 (Con~inued) Exam- Starting compound plu 2-Substltuted-2- Yleld IJMR
No. 2-Subs~Ltueed-2-cyclopentenones Aldehyde~ cycloponcenones (~ CDCI ) 64 0 0 OH 47 0.06 (9H, 3), Ch S - ~ ~ ~ OCd3 1.1-2.9 (14H, m), ~ ~ 0 ~ 2.35 t3H, 5), 3.75 -SlO ~3H, ), 3.7-4.3 t3H, m), 6.6-7.5 ' (lOH, m) 4-(4-methoxy- 2-methylthio-5-11-hydroxy-4-phunyl)bu~anul (4-methoxyphunyl)butyll-4-(4-phenoxybuty-l)-4-er~methylsilyloxy-2-cyclo-pentunone ~JJ
~n T~ble 7 (Continued) Excm- S~-relng eompound ple 2-Sub~tltuted-2- Yleld N~R
No. 2-Sub~tltuted-2-cyelopentenooe9 Aldehydee cyclopentenones ~2) (~CDCl ) 0 0 0 OH 55 0.07 (91l, ~), " ~ ~ ~ ~ 5 _ ~ ~ ~ .7--.: (31l, b~cl, _ SiO ~SLO 1.0-2.0 (1811, m), 2.5-2.9 (2~, m), - 3.7-4.0 (IC, m), 4.0 (2H, brt, 2-phenylthlo-4-~4-phenoxy- Oc~n~l 2-phenylthlo-5-(1-hydroxy- J - 6.0 112), 6.7-7.5 ; bueyl)-4-trimechyl~Llyloxy octyl)-4-(4-phenoxybutyl)-4- (11~, m) 2-cyclopentenone trlmethylsllyloxy-2-cyclo-W

~D

T--le 7 (Conclnue~) Exam- Searting compound ple 2-Substltuted-2- Yield NMR
No. 2-Sub~titueed-2-cyclopentenoneJ Aldehydes cyclopentenone~ 6CDCl ) , 66 0 0 0 OH 37 0.17 ~9H, s), CR S ~ ~,~/~_, cOOCH3 CH3S - ~ ~ ~v~ COOC~ - 1.0-2.1 ~12H, m), ~ OCh ~ ~ OCH 2.1-2.8 ~6H, m), - S10 OCH3 SiO OCH3 2.35 ~3H, s), 3.65 ~3H, g), 3.7-4.3 ~ - ~lH, m), 3.86 1-2-metbylehio-4-13-~3,4-dL- methyl 7- 2-~ethylehlo-5-(1-hydroxy-6- ~6H, s), 6.6-7.1 on me~ehoxyphenyl)propyll-4- oxoheptanoace metboxycarbonylheXyl)-4-t3- ~4H, m) trimeehylsilyloxy-2-cyclo- ~3,4-dimeehoxyphenyl)propyl]-4-pencenone trimethylsilyloxy-2-cyclo- ~J
penecnone ~J~
~n ~C
.

Table 7 (ContLnued) Exam- Starting compound ple 2-Sub~tituted-2- Yield NMR
No. 2-Sub~el~uced-2-cyclopeneenone~ Aldehydes cyclopencenones (2) (~CDCl ) 67 0 O 0 OII 48 0.0fl (9lI 9), 0.~3 ~ ~ ~ COOCH
- CH3S ~ ~C0OCH3 CH3S ~ \ I (9H, d, J - 4.5 IIz), ~ y ~ ~ 0.9-2.9 (24H, m), - SiO _ SiO 2.35 (3II, s), 3.68 (3II, ~), 3.7-4.I
` (IH, m), 6.86 2-menhgltbio-4-(3~7-dimethyl- methyl 7- 2-methylthio-5-(1-hydroxy-6- (IH, s) oceyl)-4-erimethylsilyloxy-2- oxohepeAnoaee meehoxychrbonylhexyl)-4-(3,7-cyclopentenone dimechyloceyl)-4-erimeehyl-silyLoxy-2-cyclopeneenone ~n ~n T~ble 7 ICo=el~c~d) Exam- Starting compound ple 2-Substl~uted-2- Yleld NMR
No. 2-Substituted-2-cyclopentenones Aldehydes cyclopencenones ~ CDCl ) 68 0 O O OH 42 0.05 ~9H, s), 3 ~ ~ ~ ~ 3 3 ~ ~ COOC113 0 7_1 0 (311, brc), ~ 1.0-2.9 ~18H, m), _ SiO - SiO 2.36 (3H, a), 3.69 (3H, s), 3.7-4.0 (IR, m), 6.87 ~' 2-me~hylthio-4-(1-hexynyl)-4- me~hyl 7- 2-mechylthlo-5-(1-hydroxy-6- (IH, s) trime~hylsllyloxy-2-cyclo- oxoheptanoate methoxycarbonylhexyl)-4-(1-pencenoDe hexynyl)-4-trl~e~hylsilyloxy-2-cyclopencenone _ la~ - :

~ 1 335599 E ~. O ~ ~

--I --^ =^ G ~ ~"CD
2 Q ~ O
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r~
oco or~~ = S S
o o _~ _ _ _ _ _ _~ _ P
S
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K
O_l~ j o ~ .C ' 'C -I
o =~ C~

~ , , SC~l _ V ~ I
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X
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Z `O

Table 7 (Contlnued) f Exam- Starelng compound ple 2-Sub9tltuted-2- ~ Yleld NMR
No. 2-Substltuted-2-cyclopentenones Aldehydes cyclopentenones (l) ~CDCl ) 0 0 O Oll 51 0.06 ~9IJ, 9), 1.25 C113S ~ ~ . ~ / COOC~13 C113S _ ~ J `~ C~OCII ~311, ~) 1.1-2.:
CH3 C83 (12H, ~), 2.36 , SlO _ S~0 (311, s), 3.68 (IH, ~), 6.87 2-methylthlo-4-methyl-4-trl- methyl 7- 2-methylthio-5-(1-hydroxy-6- (IH, ~) ~ethyl~llyloxy-2-cyclopentenone oxoheptanoate methoxycarbonylhexyl)-4-methyl-4-trlmethylsilyloxy-2- ~J~
cyclopentenone ~J~
~n , T-ble 7 (Continued) Exam- Starclng compound ple 2-Substituted-2-Yleld NMR
No. 2-Substieuted-2-cyclopentenone~ Aldehydes cyclopentenones (Z) (~CDCl ) 71 0 0 0 Ob 76 0.19 (9H, 9), 3 ~ ~ ~ 3 3 ~ COOCI13 0.7-1.0 (3II, brt), ~ \ ~ ~ 1.0-2.2 (23H, m), - Si0 -,Si0 2.31 (2H, t, - ~ 7.2 I~z), 2.35 (3I~, 9), 2.45 ~' 2-methyltbio-4-oct91-4-tri- methy 7- 2-metbylthio-5-(1-hydroxy-6- ~IH, d), 3.67 metbylsilyloxy-2-cyclopeDtenone o~obeptanoate m~thoxycarbonylhexyl)-4- (3H, a), 3.a-4.1 octyl-4-trimethylsilyloxy-2- (IH, m), 6.75 ~J~
cyclopentenone (IH, s) ~J~
~n - 152 - l 335599 Example 72 SYnthesis of 5-(1,4,7-trihYdroxY-2-he~tenyl~-4-hydroxy-2-methylthio-4-(4-phenoxybutYl)-2-c~clo-pentenone O OH OSi ~

MeS OSi -OPh osi ,,~, O OH OH

MeS _ r~ ~r ~ ~ ~H
- 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 lH-NMR CDC1 1.1-2.2 (15H, m), 2.35 (3H, s), 2.c-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), /.1-7.5 (2H, m).
Example 73 S~nthesis of 2-methylthio-5-~1-hvdroxy-6-methoxy-carbonylhexyl)-4-hydroxy-4-octyl-2-cyclopentenone O OH

MeS ~ ~ COOCH3 \\l ~~
osi O OH

MeS ~ ~ / COOCH3 /\~~
OH -To a solution of 63 mg of 2-methylthio-5-(l-hydroxy-6-methoxycarbonylhexyl)-4-octyl-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 71 dissolved in 6 ml of acetonitrile was added 130 ~1 of pyridine. A hydrogen fluoride-pyridine solution (260 ~1) 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 colu~n chromato-graphy to give 2~ mg (yield 41%) of 2-methylthio-5-(1-hydroxy-6-methoxycarbonylhexyl)-4-hydroxy-4-octyl-2-cyclopentenone.
Spectrum data H-NMR CDCl3 ~
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-hvdroxv-2-methylsulfinvl-4-(4-phenoxybutyl)-2-cyclo-pentenone O OH OH

MeS -- ~ ~
OPh OH

O OH OH

MeS ~ ~ OH
OPh OH

To a solution of 35 mg of 5-tl,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 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, 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.

~ 1 335599 S~ectrum 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 Svnthesis of 5- r 4,7-bis(t-butyldimethylsilyloxY)-2-heptenylidenel-2-methylthio-4-(4-Phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone O OH OSi ~

MeS ~ ~Si ,~ -OPh osi _ O osi ~, MeS ~ ~' OSi ,c +
~ OPh OSi - ~ (E) ,,, sio ~\ OSi%
O
Jl I
MeS ~ ~ (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-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 hydrogensulfate 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 of 5-[4,7-bis(t-butyldimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-- trimethylsilyloxy-2-cyclopentenone.
Spectrum data Less polar isomer (F) lH-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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- 158 - l 335599 r,~l ~ ~ f_ I
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r.~l O -- r, Ei a~ -r~ _I O
X CL Z

Table 8 (Continued) (~

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

79 O OH O 71 0.09 (9H, s), 1.0-2.0 1~ ~ COOCH3 J~ ~ COOCH3 (lOH, m), 2.0-2.8 Cll3S ~ CH3S ~ ~ (5H, m), 2.3S (311, s), ~ OCH3 ~ OCH3 3.63 (3H, s), 3.84 _ SiO OCH3 - SiO OCH3 (6H, s), 4.8-5.2 -~lH, m), 6.7-7.1 (4H, m) 2-methylthio-5-(l-hydroxy-6- 2-methylthio-5-(6-methoxy-methoxycarbonylhexyl)-4-[3- carbonylhexylidene)-4-[3-(3,4-(3,4-dimethoxyphenyl)propyl~- dimethoxyphenyl)propyl]-4- W
4-trimethylsiIyloxy-2-cyclo- trimethylsilyloxy-2-cyclo-pentenone pentenone ~n ~_ 1 3355~

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- 166 - l 3~99 EX2.~D1~ 85 -Syntheses of 5-~(Z)-4,7-dihydroxy-2-he~tenYlidenel -2-meth~lthio-4-(4-~henoxybutylidene)-2-cYclo~entenone and 5- r z ) -4,7-dihYdroxv-2-he~tenYlidene~-4-hYdroxY-2-methylthio-4-f4-~henoxYbutyl)-2-cyclopentenone = sio Y \~\ os O ~ i MeS \\ 1- ~
/ - OPh osi _ ~ 0 O
'g MeS ~
~\/~ OPh ( G ) HO
~ OH

MeS - ~
OPh OH (H) .

To ~ solution of 9 ml of pyridine dissolved in 50 ml of acetonitrile was added, 4.5 ml of hyd~ogen fluoride-pyridine solution, under ice-cooling and stirring. A solution of 1.41 g of S-[(Z)-4,7-bis-(t-butyldimethylsilyloxy)-2-heptenylidene]-2-methylthio-- 167 - l 335599 4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 75 in 15 ml of 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 for 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.S 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-CDC13 ~
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 ~ 1 335599 ~sio ~ osi--o ,~

MeS ~ `~/~ ~
OPh osi _ \ ~ OH

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 ~_ - 16g - ~ 335599 HO
~ OH
O ~

MeS ~ ~
OPh HO ~
O ~ ~

MeS ~
~ rJ \. ~ OPh To a solutlon of 20 mg of 5-[(,.')-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxy-butylidene)-2-cyclopentenone obtained in Example 85 or ~xample 86 dissolved in 3 ml of methanol was added a solution of 102 mg of sodium periodate in 500 ~1 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-t(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-3n methylsulfinyl-4-(4-phenoxybutylidene)-2-cyclopentenone.
Spectrum data H-NMR CDC13 ~
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, SH), 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-~ G -~henoxybutYlidene)-2-c~clo-pentenone and 5- r ( z ) -4,7-dihYdroxY-2-he~tenylidenel-2-methylsulfonyl-4-(4-phenoxybutylidene)-2-cvclo~entenone HO OH

O //

MeS _ OPh HO OH

O y MeS ~
\ ~ OPh ~ OH
O ~

Me' ~ OPh (I) To a solution of 280 mg of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methylthio-4-(4-phenoxybutylidene)-3n 2-cyclopentenone obtained in Example 8S 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 ~ 1 335599 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) lH-NMR CDCl3 6 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
Il \ ' MeS ~ ~
\ OPh HO ~ - OH

O /~

MeS ~ ~
~ OPh 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 - l 335599 '_ 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. Satu~ated 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.
Exam~le 90 Synthesis of 2-methylsulfonyl-S-[(Z)-4,7-dihydroxy-2-heptenylidenel-4-(4-phenoxybutylidene~-2 pentenone HO
~ OH
O ~

MeS ~ J
, OPh HO
~ OH
O ,J

~eS ~ /
Jrr OPh To a solution of 6.5 mg of 2-methylsulflnyl-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.

1 33559~

The extr-ct was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated, followed by silica gel chromatocraphy to give 3.9 mg (yield 60%) of 2-methyl-sulfonyl-5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-(4-phenoxbu_ylidene)-2-cyclopentenone.
Exa.~ le 91 Synthesis of 5-[(E)-4,7-dihydroxy-2-heptenyli~ene]-4-hydroxv-2-methylthio-4-~4-phenoxvbutyl)-2-cyclo-- Pentenone O 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 - l 335599 the concentrate was subjected to silica cei column chromatography to give 94 mg (yield 63%) or 5-[(E)-4,7-dihydrcxy-2-heptenylidene]-4-hydroxy-2-methy-lthio-4-(4-phenoxybutyl)-2-cyclopentenone.
Exam~le 92 Synthesis of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxv-2-methYlthio-4-(4-phenoxybutyl~-2-cvclo-~entenone O osi_c MeS ~ ~ .f osi=
OPh osi _ O OH
1'1 MeS ~ OH
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 - 7 33~9~

dene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclo-pentenone.
Spectrum data H-NHR CDC13 ~
1.2-2.g (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, 4X), 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 g2.

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t 335599 ~_ - 185 -Exzmple 102 Synthesis of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methYlsulfinvl-4-~henoxYbutyl-2-cyclo-pentenone HO
~ ~-- OH
O ~ _ MeS J
OPh OH
HO
'~ \ OH
o J

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 8S 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).
~ore polar isomer H-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

MeS ~
~ OPh OH

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. ~aturated aqueous 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 magnesiumsulfate. 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 H-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-t(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfinYl-4-~4-phenoxybutY1~-2-cyclo-pentenone O
Il OH
MeS ~ OH

I OPh OH

O OH

MeS ~ ~ OH
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 CDC13 ~
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 lH-NMR CDC13 ~
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 Hz), 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 - l 335599 ExamDle 105 Synthesis of 5-[(Ej-4,7-dihydroxy-2-heptenylidene~-4-hydroxy-2-methYlsulfonyl-4-(4-phenoxybutyl~-2-cyclo-pentenone O OH
' il MeS ~ ~ ~ OH
OPh OH

O OH

MeS ~ OH
O ~ 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-denel-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclopentenone.
Spectrum data lH-NMR CDCl lgo - 1 3~99 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).
Exam~le 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 ~1 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 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 ?% ) 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]-1~ 4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclo-pentenone.
Example 107 Synthesis of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylsulfonyl-4-(4-phenoxybutyl)-2-cyclo-pentenone O OH

MeS J ~ \ ~ ~ ~ OH
OPh OH

O OH

MeS ~ ~ 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 layers were combined, washed wi~h sa_urated aqueous sodium chloride and dried over-anhyc-ous magnesium sulfate. After fil;tration and conce-,tration, the concentrate was subjected to sil C2 seI column chromato-graphy to give 13 mg (yield 38~3 of --[(E)-4,7-dihydroxy-2-heptenylidene]-4-hyd~oxy-2-methylsulfonyl-4-(4-phenox~butyl)-2-cyclopentencne.
Example 108 Synthesis of 2-methylsulfinYl-4-hydroxY-5-(6-methoxycarbonylhexylidene)-4-octvl-2-cyclo~entenone MeS _ ~ ~, COOCH3 '~

MeS ~ ~ ~COOCH3 \~

To a solution of 12 mg of 2-methylthio-4-hydroxy-2S 5-(6-methoxycarbonylhexylidene)-4-octvl-2-cyclopentenone obtained in Example 101 dissolved in 2 ml of dichloro-mothane was added 6.5 mg of 3-chlo~operbenzoic 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 ch-omatography to obtain 7.3 mg (yield 61%).
Spectrum data H-NMR CDC13 ~
0.86 (3H, t, J = 5.7 Hz), 1. -2.1 (21H, m), 2.2-2.5 (2H, m), 2.5-3.0 (2~:, m), 2.87 - 193 - ~ 335599 (3~, s), 3.68 (3H, s), 6.72 (lH, t, J = 7 Hz), 7-70 (lH, s).
Exam~le 109 Synthesis of 5-[(Z)-4,7-dihydroxy-2-heptenylidene]-2-methvl'hio-4-methoxY-4-(4-~henox~butyl)-2-cyclo-pentenone HO
~ OH
O ~ _ MeS ~
OPh OH
HO
~ OH
O

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 9S%) of 5-[(Z)-4,7-dihydroxy-2-heptenyli-dene]-2-methylthio-4-methoxy-4-(4-phenoxybutyl)-2-cyclo-pentenone.
Spectrum data H-NMR C~C1 ~, - 194 -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), 6.53 (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-hvdroxY-2-meth~lthio-4-(4-phenoxYbutYl)-2-cYclopente none and 5- r ( E)-4,7-diacetoxY-2-heptenylidenel-4-acetoxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone O OH

MeS _ OH
~ OPh OE~

OAc MeS ~ OAc OPh OH (J) 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 ~1 of triethyl-amine. Under ice-cooling and stirring. 20 ~1 of acetylchloride was added, and the mixture was stirred at - 195 ~ I 3 3 5 5 9 9 0C for 2 hours. Saturated aqueous sodi~m chloride w~s added, and the mixture was extracteà with ethyl acet2te.
The extract was dried over anhydrolls sodium sulfate, filtrate and concentrated, followed ~y silica gel column chromatogra~hy to give 11 mg (yield 43%) of 5-[(E)-4,7-diace~oxy-2-heptenylidene3-4-hydroxy-2-- me~hylthio-4-(4-phenox~Dutyl)-2-cyclo~entenone (J) and 4 mg (yield i7%) of 5-[(E)-4, 7-diacetoxy-2-h?ptenyli-dene]-4-acetoxy-2-..methylthio-4-(4-phenoYybutyl-2-cvclo-pentenone (K).
Spectrum dzta H-NM~ CDCl3 ~
(J) 1.1-2.1 (llH, m), 2.01 (3H, s), 2.13 (3H, s), 2.36 (3H, ~), 3.6-4.5 (5H, m), 6.0-6.5 (lH, m), 6.6~ (lH, s), 5.7-7.2 ~H, m), 7.2-7.5 (3H, m).
(~) 1.1-2.1 (lOH, m), 2.01 l3H, s), 2.04 (3H, s), 2.13 ( 3~T, S ), 2. 35 ( 3H, s), 3 . 6-4.5 (5Fi, m~, 6.0-6.5 (lH, m), 6~64 (lH, s), 6.7-7.2 (4H, m) 7.2-7.5 ( 3n, m).
Example 111 Synthesis of 2-methylthio-5-(6-c~rboxvhéxylidene)-4-hydroxy-4-octyl-2-cyclopen~enone o I~eS~ ~ COOCH3 \/
OH

- MeS ~ ~ COO¢H~

OH

To a solutlon of 16 mg of 2-methylthic,-9-hydroxy-5-(6-methoxycarbonylhexylidene)-4-octyl-2-cyclc~entenone obtained in Example 101, dissolved in 1 ml o 2cetone, 11 ml of O.lM phosphate buffer of pH 8 was ad~d. Under stirring, 1.5 mg of pig liver esterase was acced, and the mixture was stirred at 30 - 35C for 130 :-ours.
After the mixture was adjusted to pH 4 with O.lN hydro-chloric acid, ammonium sulfate was added to s-_uration and the mixture was filtered with addition of ~thyl acetate. The filtrate was extracted with eth.-l acetate, the organic layers were combined and washed w th saturated aqueous sodium chloride. After dry-~g over anhydrous magnesium sulfate, filtration and c~ncen-tration, the concentrate was subjected to sil ca gel column chromatography to give 7.7 mg (yield 4 ~) of 2-methylthio-5-(6-carboxyhexylidene)-4-hydrox.--4-octyl-2-cyclopentenone.
Spectrum data lH-NMR CDC13 ~
0.86 (3~, t, J = 5.7 Hz), 1.1-2.2 (22Ht m), 2.2-2.5 (2H, m), 2.36 (3H, s), 2.5- .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. L1210 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.

E
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- 200 - l 3 3 5 5 9 9 Exam~le 113 Determinztion ~1) of bone formation activity Human osteoblast (SAM-l, 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 ~-glycer^phosphoric acid salt, followed by treatment for 25 days. The cell layer W2S washed with Hank's solution and the al~ali phosphatase activity then measured by absorption at OD4l0. 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 Rese2rch Communication Vol 145, No. 2, 1987, p. 651). The results are shown in Table 11.

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V ~ V
0 0 ~
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Z ; O r I o t~ +l +l +l o -- ~ V O V
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r~ C r~ + I + I + I
r ~ ~ ~o V V
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o .

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~ ~1 1 ~.

'_ 1 335599 Exam~le 114 Determination f2) of bone formation activitv 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 L0 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.

- ~3 - 1 335599 o CO ~ ~r 'D a ~ o cn 0~ 0 o~
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, ' ' .1 tn ~. t~ ra Example 115 Determination ~3) of bone formation activitv 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 OD415. Next, calcium and phosphorus were extracted with a 2N
hydrochloric acid solution and quantitated.
The results are shown in Table 13.

.~ U7 ao _I o r~

.~ ~ ~ +l a ~, _ o o U~
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Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. 2-substituted-2-cyclopentenones represented by the formula (I-c-l):

.... (I-C-l) wherein R1 represents a substituted or unsubstituted hydrocarbon group having 1 to 10 carbon atoms in which the substituent of the substituted group is selected from a hydroxyl group, a tri(C1-C7)hydrocarbonsilyloxy group, a halogen atom, an alkoxy group, an acyloxy group, an acyl group, an alkoxycarbonyl group and a carboxyl group;
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, 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 atoms, 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 protecting group of the protected hydroxyl group.