JPS60139644A - (3'-alkoxy-1'-alkenyl)-cis-bicyclo(3.3.0)octene derivative - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (R<1> is 5-10C straight, branched or cyclic alkyl or alkenyl; R<2> and R<3> are H or OH-protecting group; R<4> is H or alkyl). EXAMPLE:3-( 4'-Carboxy-1'-butenyl-6( R )-[3'( S )-hydroxy-1'-trans-octenyl]-7(R)-hydroxy-(1S,5S)-cis-bicyclo[3.3.0]oct -2-ene. USE:Intermediate for the synthesis of 9(0)-methano-DELTA<6(9alpha)>-PGI1 useful as a remedy or preventive for circulatory diseases. PREPARATION:The compound of formula I can be produced by (1) introducing methylene group to the allylcyclopentanone derivative of formula II, (2) hydrating the resultant allylcyclopentylidene derivative of formula III, (3) oxidizing and dehydrating the obtained hydroxymethylcyclopentane derivative of formula VI, and (4) reacting the product with 3-carboxypropylphosphonium bromide.

Description

Detailed Description of the Invention The present invention is based on the general formula (wherein 1 is a linear, branched, or cyclic alkyl group or alkenyl group having 5 to 10 carbon atoms, and 2 and 3 are hydrogen atoms (3'-alkoxy-1'-alkenyl)-cis-bisic0(3,3,0]
Concerning octene enzyme conductors.

1 (3'-alkoxy-1'-alkenyl)-cis-bicyclo [3゜3.
0] The octene derivative selectively reduces the double bond of the α-chain, deprotects the hydroxyl group, and hydrolyzes the ester to form 9(0)-methanol-16(9“).
-PGI□ and its analogues (see reference side below). 9(O)-methano-Δ5(ea)-P
Gll has a strong platelet aggregation inhibiting effect, and for example, when human platelets are used, the chemically unstable PG
It is a compound that is comparable to I, and is used as a therapeutic or preventive drug for various cardiovascular diseases (see test side below).

Conventionally, 9(0)-methanol(9α)-PGI t
The methods for producing 1.3-cycloocta include (a) a method of producing P(J) through 14 steps as a raw material [Proceedings of the 103rd Annual Meeting of the Pharmaceutical Society of Japan, p. 156 (1983)]; and ←) 1.3-cycloocta. A method of manufacturing from diene through 19 steps [Proceedings of the 103rd Annual Meeting of the Pharmaceutical Society of Japan, p. 157 (1983)] is known, but method (a) requires that the raw material is Tosu, (
The disadvantages of method (b) are that the target product is produced as a racemate and that the overall yield of both U) and (b) is very low.

The present inventors have developed 9(0)-methano-Δ6(9α) from inexpensive raw materials in good yield and in an optically active form with stereospecific specificity.
As a result of intensive research aimed at producing -PGIr and its analogues, the present invention was completed after discovering that the compound of the present invention can serve as an important intermediate for achieving the objective.

The general formula ((3'-alkoxy-1'-alkenyl)-7subicyclo[3°3.0
] Octene sieve conductor can be manufactured according to the reaction formula below.

In addition, the hydroxyl group in the present invention is a tetrahydropyranyl group, a methoxymethyl group, a 4-methoxytetrahydropyranyl group, a 1-ethoxyethyl group, a 1-methyl-1-methoxyethyl group, and a butyl group. Examples include dimethylsilyl group, diphenyl-t-butylsilyl group, benzoyl group, acetyl group, etc., and kL3 is 1
-butyldimethylsilyl group, benzoyl group, acetyl group, tetrahydropyranyl group, methoxymethyl group, 4-
Methoxytetrahydropyranyl group, 1-ethoxyethyl group, 1-methyl-1-methoxyethyl group, dipheny A,
-t-butylsilyl group etc. can be illustrated.

R"0 0) Lm BaoOR" R鵞0 0几3 (In the formula, R1 is a straight chain, branched or cyclic alkyl group or alkenyl group having 5 to 10 carbon atoms, R2 and 几3 are a hydrogen atom or a hydroxyl group (4 is a water atom or an alkyl group.) [First step] This step is carried out by methyleneizing the allylcyclopentanone spinner represented by The allylcyclopentanone fermentation conductor represented by the general formula cyclobentenones represented by the general formula (in the formula, kL+' is the same as the above definition, and R8 represents an aqueous group or an L1-pentynyl group). It is produced by reacting with an organic copper compound derived from (see Japanese Patent Application Laid-Open No. 11857-171965).

Examples of the compounds obtained as described above include (2(ro)-allyl-3(homogeneous(3'(8)-t-butyldimethylsilyloxy-1'-trales-octenyl)-4
(b)-1-butyldimethylsilyloxy-1-cyclopentanone), (2@-allyl-30-[3')-t
-butyldimethylsilyloxy-gi-cyclopentyl-
1'-)9-supropenyl]-4(11-t-butyldimethylsilyloxy-1-cyclopentanone), (2
■-Allyl-3■-[3'(S)-t-butyldimethylsilyloxy-4'-methyl-1'-trans-octenyl2-40-t-butyldimethylsilyloxy-1-
cyclopentanone), etc.

The methylenation reagent used in the methylenation reaction of this step is a mixed reagent of methylene bromide-titanium tetrachloride-zinc ((a, LOmbardO+Tetrahe
drone Lett, + 23* 4293 (19
82) ) or using Johnson reagent (C0H,
Johnson.

J,) L, 8hanklin, Le A, Kirchof L.
J, λm.

Chem, 8oc, , 95.6462 (197
3) It is difficult to use ).

This step is preferably carried out in a solvent; for example, when using the former reagent, a mixed solvent of a halogenated solvent such as methylene chloride and a ether solvent such as tetrahydrofuran can be used; Ether thread solvents such as tetrahydrofuran can be suitably used.

For woodworking i, the reaction proceeds smoothly by selecting a range of '-so c to 60C.

[Second Step] In this step, the allylcyclopentylidene derivative represented by the general formula obtained in the first step is subjected to a hydration reaction to obtain a human oxymethylcyclopenkune derivative represented by the general formula 2〇. It is manufactured.

The hydration reaction in this step is carried out by hydroboration and oxidation. In the hydroboration, for example, a hydroboration reagent such as 9-BBN (9-borabicyclo[3,3,1)nonane), dithiamylborane, thexylporan, etc. can be used. The amount of hydroboration reagent used is usually 1 to 3 times.

When carrying out the reaction, it is desirable to carry out the reaction in a solvent.
For example, ether thread solvents such as tetrahydrofene, diglyme, diethyl ether, etc. can be used.

The reaction proceeds smoothly at 11-25C to room temperature.

Historically, this process involves hydroboration followed by oxidation without isolation of the product. For oxidation, a silifying agent such as hydrogen peroxide can be used. When oxidizing hydrogen peroxide, it is preferable to use it in a basic state, such as sodium hydroxide. The amount of oxidizing agent used is 5 to 15 equivalents.

The reaction proceeds smoothly in chambers 1NA to 80C.

In this step, the compound produced by hydroboration using, for example, 9-HBN is presumed to have the following structure.

[Step m3] This step oxidizes the hydroxymethylcyclopentane derivative obtained in the second step and cleared by the general formula,
By dehydration, a bicyclo[30,3,0]octenyl aldehyde derivative represented by the general formula ω can be produced.

For oxidation, for example, dimethyl sulfoxide oxalyl tetralide, dimethyl sulfoxide-sulfur trichloride pyridine complex, etc. can be used. The amount of the oxidizing agent to be used is usually 1 to 5 equivalents.

The reaction is preferably carried out in J111I, and can be carried out using, for example, a halogenated hydrocarbon such as methylene chloride.

The reaction varies depending on the type of oxidizing agent, but it proceeds smoothly at temperatures as low as 70C! , Suya. 3. To obtain the oxidation product of this step, add a tertiary amine such as triethylamine or diisopropylethylamine to the reaction mixture =7. Ot:' ~ This is carried out by processing at room temperature.

The next step is dehydration.

Dehydration is carried out in the presence of a dragon catalyst. As acidic catalysts, acid-ammonium salts can be used. Acid-ammonium salt catalysts can be formed from acids and amines.

Examples of acids that can be used include trifluoroacetic acid, toluenesulfonic acid, camphorsulfonic acid, and vinegar m. Examples of amines that can be used include dibenzylamine, diethylamine, dimethylamine, diisopropylamine, piperidine, pyrrolidine, piperazine, and the like. These acids and amines can be appropriately selected and used in combination, but a catalyst that is a combination of trifluoroacetic acid and dibenzylamine is particularly preferred since the desired product can be obtained in good yield.

The amount of catalyst to be used may be about 0.2 equivalent, but in order to make the reaction proceed rapidly, it is preferable to use about 1 equivalent.

In conducting the reaction, it is desirable to use a jii medium, and aromatic hydrocarbons such as benzene, toluene, and xylene can be used.

The reaction temperature line can be selected from room temperature to 100C, but in order to carry out the reaction smoothly, it is preferably carried out within the range of 50U to 70U.

[Fourth step] In this step, in the presence of a base, the bicyclo(3,3,0)octenylaldehyde salt conductor represented by the general formula M obtained in the third step and 3-carboxypropylphosphonium bromide are combined. is reacted, and is expressed by the general formula (■) (
A 3'-alkoxy-1'-alkenyl)-cis-bicyclo(3,3,0)octene derivative is produced.

This step needs to be carried out in the presence of a base.

As the base, t-butoxypotassium, butyllithium,
Although the sodium salt of dimethyl sulfoxide and the like can be used, it is preferable to use t-butoxypotassium in order to carry out the reaction efficiently.

Amount of base to be used: The base is usually used in an amount of 1 to 1.2 equivalents based on the above-mentioned 3-hydroxyl phosphonium bromide as the raw material.

In carrying out the reaction, ether solvents such as tetrahydrosilane, dimethoxyethane, and diethyl ether can be suitably used, but there are no limitations as long as the solvent does not participate in the reaction.

The reaction proceeds smoothly by selecting a reaction temperature in the range of OC to 50 tl'.

The compound obtained in this step is usually produced as a free carboxylic acid, but for the reaction in the next step, it is isolated as an ester using the conditions of diazomethane or alkyl halide-diazabicycloundecene-acetonitrile. be able to. The conversion into an ester can be carried out by a method that can be easily performed by a person skilled in the art [Step 5] This step is carried out by converting the compound (3'- The alkoxy-1'-alkenyl)-cis-bicyclo(3,3,0)octene derivative is catalytically reduced, and only the disubstituted olefin in the α-chain is selectively reduced. Bicyclo(3,3,0)
It manufactures octene I conductors.

Catalysts that can be used include palladium catalysts such as palladium-carbon and palladium black, Wilkinson's catalyst, platinum, nickel and the like, but Wilkinson's catalyst is preferably used in order to carry out the reaction efficiently. It is sufficient to store the catalyst at a storage capacity of about 8 mils.In carrying out woodworking, hydrogen may be reacted at normal pressure or may be reacted under pressure.

It is desirable to use a solvent to carry out the reaction, and for example, alcohol solvents such as methanol and ethanol, ester solvents such as 61:acid ethyl ester, and aromatic solvents such as benzene can be used.

The reaction proceeds smoothly by selecting a temperature in the range of -25C to 60C.・Although the .(3'-alkoxy-1'-alkenyl)-cis-bicyclo(3,3,0)octene derivative of the present invention has an asymmetric carbon atom in the molecule, in the present invention, It includes the R configuration or S configuration of these asymmetric carbon atoms, or a mixture thereof in any proportion.

Hereinafter, the present invention will be explained in detail with reference to Examples and Reference Examples.

Reference example 1 0 (2■-allyl-3(b)-(a'(S)-t-butyldimethyllsilyloxy-1'-trans-octenyl)-4(b)-1-butyltadimethylsilyloxy-
1-cyclopentanone) (707~, 1.44 mmol
) in methylene chloride (7d) solution at room temperature with zinc-titanium chloride methylene bromide reagent (Zn-TiC1, -C
H, Br 1/THF* 7.48 aaL (approximately 1.3 equivalents) was added. After stirring for 30 minutes under the same conditions, the raw materials disappeared, so the reaction solution was poured into a two-layer system of ether-saturated aqueous sodium bicarbonate solution to stop the reaction. The ether layer was then separated and roughly extracted with φl ether. The special ether layer was washed with saturated ammonium chloride water and saturated saline, and dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was sheathed using silica gel column chromatography to obtain (2(ro)-allyl-3(ro)-(3'(8)-t-butyldimethylsilyloxy-1'-trans). -octenyl)-4 (kg
-1-Butyl2dimethylsilyloxy-1-cyclopentylidene) (652"f, 88%) was obtained as an almost colorless oil.

IH (neat): 3080.2930,2850.
1650°1460, 1360.12506n' NMRδ (CDCI,) 5.70 (m, IH) 15.41 (fn, 2H
), 4.75-5.10 (m, 41(),' 4
．． 02 (m, IH), 3.76 (IHlm) -
2,00~2.70 (nil 6H) tL4C)
(m, 8H), 0.88 (s, 21H), 0
．． 02 (s, 12H)・Mass m/z: 435 (M+-57), 42
L 393+323.303,289,229,147
9 75173゜Reference Example 2 (2■-Allyl-3(b)-(3'(S)-t-butyldimethylsilyloxy-1'-trans-octenyl)-4(b)-Sagi-butylmedimethylsilyl Oxy-
1-cyclopentylidene) (700q, 1.42mmo
9-borabicyclo(3,3,1)nonane (9-B
BN) in 'I'HF solution (7,1Qmmol, 14.
The mixture was heated under 2 #IJ temperature and stirred for 3 hours. Next, a 6N-NaOH aqueous solution (6,9#Ij
) s 30 '11. 4xOz Mizu Shizui (5,8#
1j) was added 9 drops at room temperature and stirred at 60UK for 2 hours. The reaction solution was extracted with ether, and the ether layer was washed with aqueous sodium thiosulfate and water. After drying over anhydrous magnesium sulfate, the solvent was distilled off and the residue was purified by silica gel column chromatography to give 11(s)-hydroxymethyl-2,,(8)-(3'-hydroxypropyl)-3(8)-. (3'(5)-1-butyldimethyldashi-zyloxy-1'-trans-octenyl)
-4(ro)-16-butyl dimethylsilyloxycyclopenkune) (502~.

67) was obtained as a colorless oil.

■Neat: 3350# 2930.2g5
0.1460°1360.1250m t.

NMRδ(C1)C13) 5.38 (m, 2H), 3.96 (m, 2
H), 3.59 (m, 4H), 2.83 (m
, IH) 2.16 (m.

3HL 1.10-1.80 (flm, 15)1)
IO, 87 (st 21H), 0.04 (s, 1
2H) Mass m/z: 471 (M”-57)
+ 453+ 396°379.339,325,32
1,247+ 229° 75, 73° Reference Example 3 Oxalyl chloride (0.46 J, 5.40 mmol)
methylene chloride solution (5 ml) to DM80 (0,
83m, 11.7mmol) of methylene chloride layer solution (4
(G) was added over 5 minutes under -78C, and the mixture was stirred under the same conditions for 15 minutes. To this, 41(8)-hydroxymethyl-2
(8) -(3'-hydroxypropyl) -3(8J
-(3'(8)-t-butyldimethylsilyloxy-
1'-trans-octenyl)-4(tl-t-butyldimethylsilyloxycyclopentane) (475■, 0
．． 900 mmol 1 ) of methylene chloride (3a) was added to the solution and stirred for an additional 15 minutes at -78 t:'. Under the same conditions, Torie, Chirami, N (2,50d, 18.0m
mol)', the cooling bath was removed, and the mixture was stirred for 15 minutes. Methylene chloride was distilled off under reduced pressure, and benzene (8d) and trifluoroacetate of dibenzylamine (22ON, 0.900 mmol) were added to the resulting residue at 70C.
' The mixture was stirred for 4 hours. The reaction solution was diluted with ether, washed with an aqueous ammonium chloride solution, a saturated aqueous sodium bicarbonate solution, and a saturated saline solution, and dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography to obtain (3-formyl-6(ro)-(
3'(8) -t-butyldimethylsilyloxy-1'
-trans-octenyl]-7(b)-t-butyldimethylsilyloxy-(18,58)-isubicyclo(
, 3, 3, 0) Iy pinch tact-2 en 1 (441#v
+97CH) was obtained as an almost colorless oil.

IR(neat): 2950, 2850.16B0,
1460°1360.1250crn-” NMRa (CI)CI, ), 9., f12 (st IH),, 6.73 (b
s, IH).

5.48 (+n, 2)1), 4.98 (m,
IH).

3,'76 (m, IH) r 3.24 (m, IH
).

1.10-2.80 (4 14H), 0.87, 0.9
0 (2s, 21H) + 0.03 (s, 12H)
・Mass m/z: ヰ4-'l (M4-97n, 435.35'l.

3'3'l, 317.303,202.73゜Example'1 \ 3-Carpoxyglobiltriferphosphonium bromide (321 mg, 0.748 mmol) in THF<
3. ota) Mu, and add t-butoxypotassium (
Add 16711g, 1.49mmol) at room temperature.
Stirred for 0 minutes. To the obtained red-orange ylide solution (3-
Formyl-6(b)-(3'@t-butyldimethylsilyloxy-1'-trans-octenyl]-7(c)-
1-Butyldimethylsilyloxy-(18,58)-cis-bicyclo(3,3,0)oct-2-eny) (
189” fs O, 374 mmol1)’r) IFCl
, 5117) solution and stirred for 30 minutes. The reaction solution was diluted with ether and acidified (p
H=4) After tau, the ether layer was separated. After further extraction with ether, the ether layers were combined and saturated NaCl
It was washed with water and dried over anhydrous magnesium sulfate. The residue obtained after evaporation of the solvent was dissolved in a small amount of ether, and methyl ester was obtained with an ether solution of diazomethane. The solvent was distilled off, and the residue was purified using a silica gel column chromatogram with two filters to obtain (3-(4'-methoxycarbonyl-1)
'-butenyl)-6()O-(3'(S) -t-butyldimethylsilyloxy-1'-trans-octenyl)-7(i(l-1-butyldimethylsilyloxy-(
18,58)-cis-bicyclo//'1:3.3.0)
Oct-2-ene) (194 Ki, ss%) to tυ! Obtained as a colorless oil.

IR(neat): 2950=2850-1750
．． 1460°1360.1250tan-1°NMRδ(cncl,) 6.27 (4J=16Hz* 215H,'r*N)
+6.02 (d, J=11Hz, 315H1c
is).

5.51 (rrb 4H)t 4.07 (m, I
H) + 3.70 (m + 1) 1) s 3.69 (s
o 3) IL 2.97 (m+tH)t 1.10~
2.70 (m, 16HL O, 87° 0.90 (
28,21H), 0.03 (s, 12H)-Ma
ss m/z: 590 (M”) = 534-53
3,519° Example 2 (3-(4'-methoxycarbonyl-17-butenyl)
-6(c)-[3'-tnibutyldimethylsilyloxy-1'-trans-octenyl]-7(b)-1-
butyldimethylsilyloxy(xss s8>-cis-bicyclo(:4.3.0)oct-2-ene) (31
! , 0.05mM) in a 10F, (0,5+17) solution of tetrabutylammonium fluoride'r) IP solution i(
0,16111,1M solution) was added thereto, and the mixture was stirred at room temperature for 15 hours. After stopping the reaction with saturated ammonium chloride water, THF was distilled off under reduced pressure. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After evaporating the solvent, the residue was purified by silica gel column chromatography to obtain i'3-(4'-methoxycarbonyl-1'-putenyl) -e (l(l, -
C3'(S)-Hydroxy-1'-trans-octenyl)-7CI (l-hydroxy-(IS.

58)-cis-bicyclo(3,3,03oct-2-ene) (15~) was obtained as colorless caramel (79th)
.

IR(neat): 3400,2950.174
2cm-”.

NM几δ(CDCIg) 6-30 (d+ J=16Hz, HH,trat
8).

6.02 CdIJ=I I Hz, p Hlc i
s ) *5.60 (m, 3) 1) t 5.40
(m, IH), 4.10 (m, IH)* 3.8
0 Cma IH)t 3.70 (s.

3) 1), 3.02 (Turtle IH).

[α) MO=-a 5°(c=0.466, Me
OH)Mass m/z@): 362 (7,M+L
344 (44).

326 (19)? 300 (37), 220 (5
4).

16B (41) * 178 (55), 43 (10
0) Example 3 (3-(4'-methoxycarbonyl-1'-butenyl)
-6()O-(3chamber)-hydroxy-1'-trans-
octenyl]-7a and -hydroxyl (IS).

5S)-cis-bicyclo[3,3,O)oct-2-ene 1 (15sy+ 0.04mM) with methanol-&(0
, 3d). A 10% aqueous sodium hydroxide solution (0.3d) was added at OC. After stirring with OC for 16 hours, the mixture was neutralized with a 10% aqueous hydrochloric acid solution under cooling. After distilling off methanol under reduced pressure, pt (adjusted to 3 to 4) was extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, the mortar was distilled off to give (3-(4'-carboxy-1'- butenyl)-6(
b)-(: 3'G9)-hydroxy-1'-trans-octenyl]-7(t)-hydroxy-(IL 5
8)-H:x-bisic0[3,3,0),t-2-ene (14''Li2O) was obtained as a colorless caramel.

IR (neat): 335G, 172 (h 10
9 (b 97001-”.

NM几J (CDCI m) 6.34 (d, J=16Hz+"H) + 6.0
6 (d-J=11f(z, "H), 5.65
(m.

3H), 5.45 (m, IH) + 3.10 (
m, IH).

Reference example 4 U)1 0)1 (3-(4'-methoxycarbonyl-1'-butenyl)
-6()D-(3'(S)-t-butyldimethylsilyloxy-1'-trans-octenyl) -7()O
-butyldimethylsilyloxy-(Is, 58)-
cis-bicyclo(3,3,0)oct-2-ene)(4
Benzea (0,9-
) Add RhCl (Ph , P)s (101 Da) to the solution, and incubate at 45C for 1 hour at room temperature under an aqueous stream (normal pressure).
．． Stirred for 5 hours. After removing the catalyst with a short silica gel column, the obtained residue was again subjected to silica gel column chromatography to obtain f#, and 45 kg of colorless oil was obtained.

This is combined with nato-2-butylammonium fluoride (DTHF).
Solution (0,8 tnl, I Mllll!l) 't-
The silyl ether was removed by stirring for 12 hours.

After distilling off the solvent, the residue was purified by silica gel column chromatography to obtain (3-(4'-methoxycarbonylbutyl)-6(ro)-(3'@)-hydroxy-1'-trans-octenyl). -7(b)-hydroxy-(1S
, 58)-cis-bicyclo(3,3,0)oct-2-
(20q, 69.ch) was obtained.

IR(neat): 3400.2970+2930
．． 2870°1742cIn'.

NMM2CCDCl2) 5.60 (4 2H), 5.33 (BS, IH).

4.12 (m, IH) + 3.80 (m, 1)
1).

3.69 (a, 3) 1) -3,00(rn, 1
)1)・Mass m/z: 346 (M+-H2
O)s 328s 315+3021275.247,
232,199,193゜180.179゜Reference example 5 L)k'1 (3-(4'-methoxycarbonylbutyl)-6゛■-
(3'(8)-Hydroxy, -1'-trans-octenyl]-7(ro)-hydroxy-(IS,5S)-cis-bicyclo(3,3,0)oct-2-ene)(10'
Q+ 0.027mmo supervision) with methanol-k<0.3ta
l). 1096 hydroxylated with OC) IJum water bath 1et (0,2rtrl)f was added. After stirring with OC for 9 hours, the mixture was neutralized with a 10% aqueous hydrochloric acid solution under cooling. After distilling off 1 methanol under reduced pressure, -p) was adjusted to 13 to 4 and extracted with ethyl acetate. After drying with anhydrous magnesium sulfate,
The solvent t-trade distilled off (9(0)-methanol-j6(9-P
GI, ) (10'f*, 10q%) obtained 7'Co ・I) L(neat): 3350 + 2910,285
0,1700°1450+1250m-'.

NMB δ (CDCl2) 5.60 (Turtle 2) 1) , 5.31 (b S, I
H) +4.11 (rllllIH) -3,80 (m=
1H) t a, o.

(m, IH), 0.90 (t, J=6Hz,,
3H).

1%4asa (CI, NH3) m/z: 36
8 (M"-1-NH4) Melting point near 3~79C α) j' = + 1 60 (C = 0.251 Me
OH)-Reference Example 6 (2■-Allyl-3(b)-[3'(y-t-butyldimethylsilyloxy-3'-cyclopentyl-1/-trans-propenyl]-4(b)-1- Butyldimethylsilyloxy-1-cyclopentanone) (354”I
+ 0.72 mmol) of methylene chloride (7#Il
) Zinc-titanium chloride methylene bromide reagent (Zn-TiC1,-CH2Br2/T) lF
+ 3.74 nJ + approximately 1.3 equivalents) was added. After stirring for 30 minutes under the same conditions, the raw material disappeared, so the reaction was stopped by pouring it into a two-layer system of ether-saturated sodium hydrogencarbonate IJ. Then, the ether layer was separated and further extracted with ether. The extracted ether layer was washed with saturated ammonium chloride water and saturated noble water, and dried over anhydrous magnesium sulfate. ##, Wofuekyokama, Zan f
Purified by f1t-silica gel column chromatography: (2(ro)-allyl-3(ro)-[3'(S)
-t-butyldimethylsilyloxy-3'-cyclopentyl-1'-trans-propenyl]-4(b)-
Phyldimethylsilyloxy-1-cyclopentylidene (326W, 88%) #1 was obtained as a colorless oil.

IR(neat) = 3078. , 29301 2
8501 1648°1460+ 13601.124
7crnt.

NMRa (CDCIg) s, 70 (m, IH), 5.40 (m, 2)
I), 4.70-5.05 (Q 4.) 1) p
4.02 (m, IH) e3.7g (11-L m
L 2.00-2.60 (m, 6H).

1.38 (11119H), 0.88 (s+ 1
8H).

0.02 (s, 12i().

Mass m/z: 433 (M 1,000-57), 41
9,391 Reference Example 7 To(2(c)-allyl-3(b)-(3'@)-t-butyldimethylsilyloxydi3'-cyclopentyl-1
'-trans-propenyl)-4(i(l-1-butyldimethylsilyloxy-1-cyclopentylidene)(6
989-, 1,42 mmol) and 9-borahicyclo (a
, a, i, , ) T l- of nonane (9-BBN)
i F bath liquid (7,10mm01e 14.2m!?)
tm temperature and stirred for 3 hours. Next, go to the reaction system with QN
-NaOti aqueous solution (6,9d) 7.30 tH80□ aqueous solution, dropwise solution (5,8 #Ij) under rich temperature, 60
The mixture was stirred at C for 2 hours. The reaction solution was extracted with ether,
The ether layer was washed with an aqueous sodium thiosulfate solution and water. After drying with anhydrous 4Jlt magnesium, the solvent was distilled off and the IR residue was purified by silica gel column chromatography to obtain (10-hydroxymethyl τ2(8)-(3'-
hydroxypropyl) -3@-C3'(S)-t-butyldimethylsilyloxy-3'-cyclopentyl-1
'-trans-propenyl]-4(c)-t-butyldimethylsilyloxycyclopentane) (442N9.
5996) was obtained as a colorless oil.

IR(neat): 3345.2920,2850,
1456°1360.1246crn”.

NM approximate δ (CDCI,) 5.35 (1ml, 2)1), 3.95 (m+
2) 1), 3.59 (m, 411)t 2.16
(m, 4H), 1.10-1.80 (m, 1
6) 1), 0.87 (at 18) ().

0.04 (s, 12) 1).

1Vass m/z: 469 (M”-57)*
451t 394 Reference Example 8 Oxalyl chloride (0.46 mJ, 5.40 mmol
) to methylene chloride solution (5d) in DM80 (0,83
Methyl chloride L/7 solution (4-) of IIL7+11.7 mmol was added over 5 minutes at -78C, and 1
Stir for 5 minutes. This is added to (1(8)-hydroxymethyl-2(■-(3'-hydroxypropyl)-3(婢-(
3'(S)-1-butyldimethylsilyloxy-3'-
cyclopentele-1'-trans-propenyl)-4(
1-butyldimethylsilyloxycyclopentane)
(473'F, 0.900mmo) of methylene chloride (
3#Ij) solution was added dropwise, and the mixture was further stirred at -78C for 15 minutes. Under the same conditions, triethylamine (2,50d,
18.0 mmol) was added, the cooling bath was removed, and the mixture was stirred for 15 minutes. Methylene chloride was distilled off under reduced pressure, and benzene (8d) and trifluoroacetate of dibenzylamine (0 to 0.900 mmol) were added to the resulting residue, and the mixture was stirred at 7-OC for 4 hours. . The reaction solution was diluted with ether, washed with an aqueous ammonium chloride solution, a saturated aqueous sodium bicarbonate solution, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. After evaporation of the solvent, the residue was purified using a silica gel column Chromadog 2F to obtain (3-formyl-
6(t)-[3'-1-butyldimethylsilyloxy-3'-cyclopentyl-1',) lance-propenyl□)-7(l()-1-butyldimethylsilyloxy-
(18,58)-cis-bicyclo(3,3,0,)(385q+85%)t was obtained as a colorless oil.

El (net): 2950, 2MO, 1675,
1450゜136011250 sub-1゜NMM2CCDCI3) 9.82 (s, IH), 6.72 (bs, IH)
15.45 (m, '2) 1) - 4,05 (m, IH)
, 3.76 (m.

IH), 3.23 (m, IH), 1.10-2.
80(2), 15)1), 0.87.0.90 (
Mo18) 1) * 0.03 (s, '12H) −
Mass m/z: 447
33. 357°3B7.315.301.20077
1-Example ratio =
3.0ml), and to this was added t-butoxypotassium (
167 avt 1.49 mmol) was added, and the
Stir for a minute. To the obtained red-orange ylide solution was added (3-formyl-60-[3'(he)-t-butyldimethylsilyloxy-3'-cyclopentyl-1'-trans-propenyl)-7(i(l-1 -butyldimethylsilyloxy-(Is,5S)-cis-bicyclo(3,3,0)
oct-2-ene) (189~, 0.:174mmo
The T)IF (1,5d)m solution of 1) was added and stirred for 30 minutes. Dilute the reaction solution with ether and add 4c to 10ml.
After making the mixture acidic (pH=4) with 1 mL of aqueous solution, the ether layer was separated. After further extraction with ether, the ether layers were combined, washed with saturated NaCl and 1 water, and dried over anhydrous magnesium sulfate.Solvent After distilling off, the resulting residue was dissolved in a small amount of ether and converted into methyl ester with an ether solution of diazomethane. After distilling off the solvent, the residue was separated and purified by silica gel column chromatography.
'-Methoxycarbonyl-1'-butenyl)-1n-(
3'(he)-1-butyldimethylsilyloxy-3'-
cyclopentyl-1'-)7suprobenyl)-7@
-1-butyldimethylsilyloxy-(lj, 58)-
cis-bicyclo(3,3,0)oct-2-ene), (
175av, 80cm) t-tl was obtained as a colorless p-oil.

■Neat: 2950, 4. ．． 850.17
45.1460°1358.1240a++'.

NMi(δ(CL)C13) 6.25 (d, J=16Hz, 215 trans)
.

6.01 (d, J=11Hz, 375H, cis
)+5.50 (m, 4)i),, 4.07 (m
, IH) 9.3.69 (m, IH), 3.6B,
(a, 3H)*2.9B (m.

tH), t, 10-2.70 (met'yH)*
0.87゜0.90 (2 turtles 18M) + 0.03
(s, 12H).

Mass m/z: 588 (M”)t 532+
531+ 517 Example 5 (3-C4'-methoxycarbonyl-t'--f-tenyl)-6■-(3'(8) -t-butyldimethylsilyloxy-3'-cyclopentyl-1'-trans-propenyl ]-7(a-t-butyldimethylsilyloxy-(18,58)-cis-bicyclo(3,3,03oct-2-xn) (81q, 0.14mM))
Cl, 5aj) lll solution, tetrabutyl 7 ammonium fluoride)' T HF solution * C0, 42ml. I M
solution) and stirred at room temperature for 16 hours. After stopping the spreading with saturated ammonium chloride water, Tl-IF was removed at the end of the ridge pressure. The aqueous layer was extracted with ethyl acetate, and the M layer was
After washing with brine, it was dried over anhydrous magnesium sulfate.

After distilling off the solvent, the residue was purified by silica gel column chromatography to obtain (3-(4'-methoxycarbonyl-
1'-Butenyl)-6(ro)-C3'(8)-hydroxy-3'-cyclopentyl-1'-)lance-propenyl)-7()O-hydroxy-(Is, 58)-7subicyclo(3 ,'3.0)oct-2-ene)(49
av+100%) was obtained as a colorless caramel.

IR(neat): 3400.1?40.1430,
1160°10901965cIn”.

NMRδ(C1)C1,) 6.22 (de J=16)1z, HH9tran
s).

5.95 (cL J=11L(z+”a cis)
+5.13~5.74 (m, 4 fluorophore 4 Nick protons>, 3.66 (s, 3H), 3.50~
4.00 (me 28) + 3.02 (m + IH
)-Mass m/z: 360 (M+), 34
2 (M”-H@CJh324 (M”-2H,0)
, 298.273°(α)g' = -3o? (c
=1.16+MeOi().

Example 6 (-3-(4'-methoxycarbonyl-11-phthynyl)-61A-(3'9%-hydrotri-3'-cyclopentyl-1'-')9-propenyl]-7 )−
Hydroxy-(18158')-cis-bicyclo[3,
3,0] Octo-2-Y) (50 0.14mM
) was dissolved in methanol (1, IJII7). OL
IJium aqueous solution (1,1iu/)
added.

After stirring in OC for 18 hours, add 10rIb salt solution f# under cooling.
Neutralized with liquid. After distilling off methanol under reduced pressure, p) l-
Adjust the tI to 3 to 4, extract with ethyl acetate, dry with anhydrous magnesium sulfate, and distill off the solvent to obtain (3-(4'-
Carboxy-1'-butenyl)-6(19-(3'(婢-hydroxy-3'-cyclopentyl-1'-trans-propenyl)-7(l(l-hydroxy-(Is, 5
19) -'Sisubishinoro(3,3,0)octo-2
-Ene) (43q, 89%) was obtained as a colorless caramel. "IR(neat)': 335G+ 1715,10
85,970crr1°NMRδ (CDCI,) 6-32 (d= J=16Hz, NH>t 6.0
4 (d.

J=12Hz, ”H) + 5.64 (m, 3H)
.

5.44 (m, IH) + 3.10 (m, IH
) - Reference Example 9 δS, Tsuji (3-(4'-methoxycarbonyl-1'-butenyl)
-6(c)-(3'(s) = t-butyldimethylsilyloxy-3'-cyclopropyl71'-trans-
propenyl]-7(b)-t-butyldimethylsilyloxy-(18', 5S)-c, subicic party (3,3,
RhCl (Ph3
P), (10q) was added, and the mixture was stirred at room temperature for 1 hour and at 45C for 1.5 hours under a hydrogen stream (atmospheric pressure). Short silica gel, column! After removing the catalyst, the obtained fcIA residue was purified again by silica gel column chromatography and mudgraphy.
Two capes of colorless oil were obtained. To this, a solution of tetrabutylammonium fluoride 'I:ilF m (o, 5IA
The mixture was stirred with MrM for 12 hours to remove the silyl ether. After distilling off the solvent, the residue was purified by silica gel column chromatography.
methoxycarbonylbutyl) -6'(R-(3'(8
)-Hydroxy-3'-cyclopentyl-1'-trans-propenyl)-7@-hydroxy-(18°58)
+ to shisu::shi/a (3,3,0)yl'or
To-2-ene) (17q, 60%) was obtained as a colorless viscous oil.

IR(neat) 2 3400. 2960. 28
80. 1740crn-1°NMRδ (CDC1,) 5.61 (2)L m), 5.32 (11-L
bs), 3.85 (2H, mL 3.67 (3)1
．． S), 3.00 (lam) 11.10-2.6
0 (26)L m).

Mass m/z: 344 (M"-18L 32
6 (M+-36), 300, 2.75, 243, 23
2゜225, -199-193+ 183,181゜1
80e 179,141,119,117°105.9
3,91.81,79,69.67゜55.41・' Reference Example 10 0H (:a-(4'-methoxycarbonylbutyl)-6(L
() -(3'<8) dihydroxy-3'-cyclopentyl-1'-trans-propenyl]-7(ro)-hydroxy-(IS, 58)-cis-bicyclo[3,3,
0]o/)-2-x:y) (10mg, 0.0
27 mmol was dissolved in methanol (0.3 mm). O
10-Sodium hydroxide aqueous solution (0.2#l/)t
-Added. After stirring with OC for 9 hours, the mixture was neutralized with a 10% aqueous hydrochloric acid solution under cooling. Distill off methanol under reduced pressure, pH 3
-4 and extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, the solvent was removed to give (3-(4'-carboxybutyl)-6(ro)-(3'(S)-hydroxy-
3'-cyclopentele-1'-) lance-propenyl]
-70-hydroxy-(18,58)-cis-bicyclo(3,3,0)/"oct-2-ene) (10~,1
0(1) was obtained as a colorless solid. When this was recrystallized from ethyl acetate-hexane, a colorless poison with a melting point of 115-116C was obtained.0IR(KBr): 3430(O)i), 2960.
1700°1655cm-”.

NMkL δ (CDCI, ) 5.60 (2a m) I5j2 (lHlbs).

3.90 (2)L m), 3.00 (1M, m
).

1500~2.70'(25)L m)-Mass (
CI, N)13) m7/Z: 366 (M”
+NH4) Reference Example 11 H (3-(4'-me)=?dicarbonyl-1'-butenyl) -fl-(3'(8) dihydroxy-1'-trans-octenyl]-7(ro)-hydroxy-( 18,5
8)-cis-bicyclo[:a, 4. o] Oct-2-ene) (15aF, '0.041mA4) in benzene (0,5d) solution) LhCl (Ph3□1') 3
(-5'q) was added, and the mixture was stirred at room temperature for 1 hour and at 45C for 1.5 hours under a hydrogen stream (atmospheric pressure). The catalyst was removed using a short silica gel filter, and the resulting residue was purified by 2-layer chromatography on silica gel to obtain 9 kg of colorless oil. This was dissolved in methanol (0.2m).

10% sodium hydroxide aqueous solution (0.1 ml) in OC
) was added. After stirring with OC for 9 hours, the mixture was neutralized with a 10% aqueous hydrochloric acid solution while cooling. After distilling off the metatool under reduced pressure, p
The mixture was extracted with H3-4 and extracted with ethyl vinegar. After drying with anhydrous sulfuric acid (7 um), the solvent was distilled off (3-(
4'-calphodt Schiffl>-6(fO-[3'(he)-human-xy-1'-trans-octenyl]-7(
b)-Hydroxy-(18,58)-cis-bicyclo(
3,,3,0)oct-2-ene) (9q) was obtained as a colorless solid. The spectral data are consistent with those obtained in Reference Example 5.

Reference Example 12 (3-(4'-carboxy-1'-butenyl)-6(ro)-(3'(8)-hydroxy-1'-trans-octenyl)-70-hydroxy-(18158)-cis-
Bicyclo(3,3,0)oct-2-ene) (14”W
+ 0.041 mM) in benzene (0.5 sJ) was added HCl (PhsP)i (5"f) and stirred at room temperature for 1 hour and at 45C for 1.5 hours under a hydrogen stream (c latent pressure).

After removing the catalyst using a short silica gel column, the resulting residue was purified again using silica gel column chromatography to obtain 43-(4'-carboxybutyl)-6(6j19).
b)-[3'(→-hydroxy-1'-trans-octenyl)-7(41-hydroxy-(IS.

58)-cis-bicyclo(3,3,O:]]octoh2
-ene was obtained as a colorless solid. The spectral data are consistent with those obtained in Reference Example 5.

Reference example 13 (3-(4'-methoxycarbonyl-1'-butenyl)
-60-[3'(8)-hydroxy-3'-cyclopentyl-1'-trans-propenyl)-7(c)-hydroxy-(Is, 58)-cis-bicyclo[3°3.0
), tcuto-2-ene 1 (15ql 0.04,1m
Add hcl to the benzene (0,5IrLl) solution of M)
(Ph3P).

(5q) Add t, under hydrogen stream (normal pressure), at room temperature, 1
The mixture was stirred at 45C for 1.5 hours. After removing the catalyst using a short silica gel column, the resulting residue was purified again by silica gel column chromatography to obtain 4#'s colorless viscous oil. This was dissolved in methanol (0.27d). 10% aqueous sodium hydroxide solution (0,
1d) was added. After stirring in OC for 9 hours, under cooling, 10%
Neutralized with salt and aqueous solution.

After distilling off Metame→ under reduced pressure, the pH was adjusted to 3 to 4, extracted with ethyl acetate, dried over 0.05% magnesium, and the solvent was distilled off to give (3-(4'-carboxybutyl)-6). (
b)-(3'-)-hydroxy-3'-cyclobenyl-1'-)lans-propenyl) = 7 (l(l-
Hydroxy-(18,58)-cis-bicyclo(a,3
．． o) Octo-2-king) (8rn?) was obtained as a colorless solid. Is spectral data just a piece of paper? This is consistent with that obtained in 1J10.

Reference example 14 (3-(4'-carboxy-1'-butenyl)-60-
(3'(S)-hydroxy-3'-cyclopentyl-1
'-) lance-propenyl]-7(c)-hydroxy-
(18,58)-cis-bicyclo(3,3,0)oct-2-xn) (14ay, 0.041mM) in benzene (0,5a/) solution with H, hcl (Ph,P)S
The catalyst was removed using a short silica gel column, and the resulting residue was re-coated with silica gel column chromadog 2. *G split at fee, 7m9 (3-
(4'-carboxybutyl)-6(1◇-113'(8
)-Hydroxy-3'-cyclopentyl-1'-)lans-propenyl]-7(ro)-hydroxy-(Is, 5
8)-cis-bicyclo[:3.3.0]oct-2-ene) was obtained as a colorless solid. The spectral data match that obtained in Hoko Example 10.

Patent Applicant Procedures Amendment (Spontaneous) April 2, 1980 Commissioner of the Japan Patent Office Mr. Kazuo Wakasugi 1゜ Incident Representation 1980 Patent Application No. 244695 26 Name of the Invention (31-Alkoxy-I'-Alkenyl) -cis-bicyclo[3,3,03 octene derivative 3゜Relationship with the case of person making an amendment Column 5 of “Detailed Description of the Invention” of the patent applicant's specification, Contents of the amendment (1) Specification of the present application No. Page 3, line 9 [(Delete the sword referring to the test example below.

(Xiong, page 8, line 3, r (Vl) J is corrected to "(■)", and line 6, "(■)" is corrected to "(■)".

(3) The next best thing to “n)” on page 9, line 14, “, (2(R
)-allyl-3(f'9- (3'(8)-tetrahydropyranyloxy-1'-) lance-octenyl]-4
(b)-tetrahydropyranyloxy-1-cyclopentanone), (2(b)-allyl-3(b)-[3''(S
)-tetrahydrobyranyloxy-31-cyclopentyl-1'-)lans-propenyl)-4(1()-tetrahydropyranyloxy-1-cyclopentanone).

(4) On page 15, line 9 of the same page, change "...promido" to "...
Corrected to "Promid".

(5) On the bottom line of page 27, "...6 (to) - (a' (
s) t..." to "...6(8)-(3'@)-1
〇(6) Correct “6(6)” written in the following part to r6(8)J
Correct.

Page Row 25 10 28 14 30 5 31 8 33 1 and 11 36 2 and 17 382-3 516 48 6 49 3 51 5 52 8゛54 2 and 12 Page Row 57 2 and 17 59 4-5 60 6 62 2 and 17 63 8-9 64 8 65 4 66 10 67 4-5 68 4'' (7) On page 57, line 3, ``cyclopropyl'' is corrected to ``cyclopentyl''.

(8) Insert the following between lines 9 and 10 on page 68 of the same page.
-Allyl-3(c)-(3'(S)-tetrahydropyranyloxy-11-trans-octenyl)-4(b)
-tetrahydropyranyloxy-1゛, cyclopentanone) (8684,2 mmol) from (3-formyl-6(8) -(3'(S)-tetrahydropyranyloxy-1'-trans-octenyl)- 7(R)-Tetrahydropyranyloxy-(18,58)-cis-bicyclo[3°3.0]oct-2-ene) (446 units, total yield 50 units) was obtained as a nearly colorless oil. Ta.

IR(neat):2950,2850.1680cI
rL.

Kukan J (CDCI) F81 (s, IH), 6.75 (bs, IH), 5.4
4 (m, 2H), 4. i0・Cm,QH),
3.20-4.10 (m, 7H).

Mass m/z: 446 (M+), 361° Example 7 By the same reaction procedure as in Example 1, (3-formyl-6
(8)-(3°(8)-tetrahydropyranyloxy-
1'-trans-octenyl)-7(R1-tetrahydropyranyloxy-(Is, 58)-cis-bicyclo[
31310] Oct-2-ene) (446 Akebono.

1 mmol) from (3-(4'-methoxycarbonyl-11-butenyl)-6(8)-(3'(8)-
-7(R)-tetrahydropyranyloxy-(
Is, 58) -'i miss-bicyclo3.3pO]oct-2-enej (147ζ.

90) was obtained as an almost colorless oil.

IR (neat): 2950, 2850.1745cm
.

Width J (CDCl2) 6.25 (d, J=l 5Hz, 1/3H, t
rans).

6.02 (d, J=l lHz, g/3H, c
is).

5-50 (m, 4H) -4-60 ('', 2)
(), 3-40 to 4.10 (m, 6H), 3.6
9 (s, 3H), 2.97 (m, IH), 0.8
7 (t, J=7Hz, 3H).

Mass rr7z:530(M+), 499,
445.

Example 8 13-(4'-methoxycarbonyl-1'-)f-nyl)
-6-(8)-'(3'(8)-tetrahydropyranyloxy-11-trans-octenyl]-7@-tetrahydropyranyloxy-(1B, s8)-cis-bicyc-o, (3y3 qO)- 2-ene) (4
70tl#.

0.89 mmol) in vinegar, acid (4.7 ml/water (1
, k), M (1,6 m) in a mixed solvent i and heated to an external temperature of 4
Heated at 5°C for 6 hours. After acetic acid was distilled off under reduced pressure, saturated double blind water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography to obtain (3-(4'-methoxycarbonyl-1
°-butenyl)-6(S)-(3°(S)-hydroxy-1'-)lans-octenyl]-7(ro)-hydroxy-(Is, 58)-cis-bicyclo[(3,3, 0
) Oct-2-ene) (261ty) was obtained as a colorless caramel (81%). Various spectral data are shown in Example 2.
It matched the spectral data of the substance obtained in .

Reference Example 16 By the same reaction procedure as in Reference Examples 6 to 8, (2(R)-allyl-3(6)-[3'(S)-tetrahydropyranyl, t-t-cy3-cyclopentyl-1'- (8644,2 mmol)-1()-tetrahydropyranyloxy-1-cyclopentanone)
) from (3-formyl-6(S)-(3'(8)-tetrahydropyranyloxy-31-cyclopentyl-11
-trans-propenyl)-7()Q-tetrahydropyranyloxy-(Is, 58)-cis-bicyclo(3,
3,0) oct-2-ene) (408 towns, total yield 46
H) was obtained as a nearly colorless oily substance.

IR (neat): 2950, 2850, 1680
cm-'.

NMIIL-(CDC15) 9.81 (s, IH), 6.74 (bs, IH).

5.4a (m, 2H), 4.48 (m, 2H), 3.2
0-4.10 (m, 7H).

Mass n)/z) 444 (M+), 359.

Example 9' By the same reaction procedure as in Example 4, (3-formyl-6
(8)-(3'(8)-tetrahydropyranyloxy-
3-cyclopentyl-1-trans-propenyl]-7
(b)-tetrahydropyranyloxy-(1s, 5s)
-cis-,,bicyclo(3,3,0)oct-2-ene) (4013sy, 0.92mmol) (3-
(4°-methoxycarbonyl-1-nibutenyl)-6(
Sk(3°(8)-tetrahydropyranyloxy-3-
Cyclohentyl-1-trans-propenyl)-7(R
)-tetrahydropyranyloxy-(18,58)-cis-bicyclo(3,3,0)oct-2-ene) (44
7 Akebono, 92%) was obtained as an almost colorless oil.
(neat): 2950, 2850, 1744cm
'.

NMRa (CDCI,) 6.24 (d, J=16Hz, 1/3H, trans)
.

6.01 (d, J=11Hz, V3H, cis).

5.50 (m, 4H), 4.60 (m, 2H), 3.5
0-4.10 (m, 6H), 3.68 (s, a
H), 2.98 (m, IH).

Mass rry't: 528 (M+), 49
7, 443.

Example 1O (3-(4'-methoxycarbonyl-11-butynidi-
3-cyclopentyl-1-trans-propenyl]-7
(6)-Tetrahydropyranyloxy=(18,58)
-cis-bicyclo(3,3,0)oct-2-ene (
500wf, 0.95mmo 1 ) with acetic acid (4,7
*).

It was dissolved in a mixed solvent of water (1,6id) and THF (t,6-) and heated at an external temperature of 45°C for 6 hours. After distilling off the acetic acid under reduced pressure, a residual saturated aqueous sodium bicarbonate solution was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After evaporating the solvent, the residue was purified by silica gel column chromatography to give (3-(4-methoxycarbonyl-1'-butenyl)-6(8)-(3'(
8)-Hydroxy-31-cyclopentyl-1'-trans-propenyl)-7(H)-hydroxy-(18,
58)-cis-bicyclo(3,3,0)oct-2-ene) (308 mp, 90%) was obtained as a colorless caramel. Various spectral data agreed with the spectral data of the material obtained in Example 5. "that's all

Claims (1)

[Claims] (1) (3'-alkoxy-1'-alkenyl) represented by the general formula
-cis-bicyclo(3,:1.0)octene derivative (
In the formula, 几1 is a linear, branched or cyclic alkyl group having 5 to 10 carbon atoms, R' is an alkenyl group, R' is a hydrogen atom or a protecting group for a hydroxyl group, and R' is a hydrogen atom or an alkyl group. It is the basis. ).