JPS62234060A - Punaglandin derivative and intermediate therefor - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R<1>-R<3> are lower alkyl). EXAMPLE:Methyl (5S,6R)-5,6-diacetoxy-(7E)-7[(2S)-2-hydroxy-2-n-octyl-4-chloro-5- oxo-3-cyclopentene-1-ylidene]heptanoate. USE:An anticancer agent. PREPARATION:A compound expressed by formula II (R<4> is hydroxy-protecting group) is subjected to acid hydrolysis with acetic acid or p-toluenesulfonic acid, etc., in a solvent, e.g. water, alcohol, etc., at room temperature - while heating to carry out deprotection and afford the aimed compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to punaglandin derivatives and novel intermediates thereof.

Previously, one type of prostanoid punaglandin, represented by the formula: A, was discovered by Cheuar and confirmed to have anticancer activity.

However, the total organic synthesis of punaglandin derivatives has not yet been reported.

One object of this invention is to obtain a novel punaglandin derivative [
Iconi○H (wherein R, R and R3 are the same or different and mean a lower alkyl group).

Another object of the present invention is to provide a method for producing the punaglandin derivative CI].

Examples of preferred lower alkyl groups include methinoethyl,
Examples include straight-chain or branched lower alkyl groups having 1 to 6 carbon atoms, such as propyl, isopropyl, butyl, isobutyl, secondary butyl, tertiary butyl, pentyl, and hexyl.

The inventors have prepared an optically active punaglandin derivative [! ] from 7-protected hydroxy-2-hebuten-1-ol (1) and (45)-4-hydroxy-2-cyclopenten-1-one (12) by tautomeric selection method and/or
Alternatively, we found that it can be synthesized by a stereoselective method.

The tautomerically selective total synthesis and stereoselective total synthesis of the punaglandin derivative [I] of this invention are explained by the following formula.

(In the formula, R1, R2 and R3 have the same meanings as before, and R4, R5 and R6 are the same or different and mean a hydroxy protecting group).

Suitable hydroxy protecting groups for R4, R5 and R6 include, for example, triorganic substituted silyl ether residues such as trimethylsilyl, tert-butyldimethylsilyl, etc., e.g. Acyclic ether residues such as methyl, methoxymethyl, β-methoxyethoxymethyl, etc., cyclic ether residues such as 2-tetrahydropyranyl, 4-methoxy-4-tetrahydropyranyl, etc., such as acetyl, chloroacetyl, etc. Mention may be made of the customary hydroxy protecting groups used in organic chemistry, such as ester residues, such as esterified carboxy groups such as β, β, β-trichloroethoxycarbonyl, β-trimethylsilylethoxycarbonyl, and the like.

The method for producing the target compound CII will be described in detail below.

Production i group Δ Compound (2) can be produced by subjecting compound (1) to an epoxide production reaction.

This reaction can be carried out, for example, by a conventional method as shown in Togo.

1. Compound (3) can be produced by subjecting compound (2) to an epoxide cleavage reaction.

This reaction can be carried out, for example, by a conventional method as shown in back layer (1).

Compound (4) can be produced by subjecting compound (3) to a reaction for introducing a hydroxy protecting group.

This reaction can be carried out in a conventional manner, for example, by using a silyl compound as an introduction agent.

Suitable silyl compounds include hexamethyldisilazane, trimethylchlorocyan, tertiary-butyldimethylchlorosilane, isopropyldimethylchlorosilane, N,O
-bis(tertiary-butyldimethylsilyl)trifluoroacetamide, bis(dimethylisopropylsilyl)acetamide, tertiary-butyldiphenylchlorosilane, and the like.

This reaction is usually carried out in a cooled solvent such as an ether such as diethyl ether, dibutyl ether, tetrahydrofuran, dioxane, an aromatic solvent such as benzene, toluene, xylene, ethyl acetate, dichloromethane, chloroform, acetonitrile, dimethylformamide, etc. It is carried out at a temperature that is slightly heated from below.

This reaction is effective for the reaction of organic amine compounds such as triethylamine, tributylamine, tribenzylamine, N-methylpiperidine, N,N-dimethylaniline, pyridine, imidazole, 1,5-diazabicyclo[z,z,2]octane, etc. Among these, if the amine compound is liquid, it can be used as a solvent.

Isunhoko Compound (5) can be produced by reacting Compound (4) with acetone dimethyl acetal.

The reaction can be carried out by a conventional method as shown in Example 4, for example.

The 1-produced Toyotama compound (6) can be produced by deprotecting the hydroxy protecting group of the compound (5).

Deprotection reactions can be carried out by conventional methods such as reduction.

When the protecting group is removed by reduction, in the presence of a catalyst such as platinum, palladium, lithium, nickel, etc., in a solvent such as water, alcohol, acetic acid, liquid ammonia,
The reaction can be carried out in a temperature range of cooling to heating.

Production method F Compound (7) can be produced by oxidizing compound (6).

The oxidation can be carried out by so-called Swarn oxidation.

Juttan compound (8) can be produced by oxidizing compound (7).

The oxidation can be carried out by the so-called Jones oxidation.

Compound (9) can be produced by alkylating compound (8).

Alkylation can be prepared by treating the carboxy compound obtained above with a diazoalkane such as diazomethane in a solvent such as an ether or alcohol at a temperature under cooling.

Production method (1) Compound (10) can be produced by deprotecting the hydroxy protecting group of compound (9).

The deprotection reaction can be carried out in a conventional manner, for example by solvolysis in a solvent, with or without an acid catalyst.

Suitable solvents include the aforementioned ethers, alcohols such as methanol, ethanol, isopropyl alfur, cyclohexanol, water, acetonitrile, tetrahydrofuran, and the like. Suitable acids include acetic acid,
Examples include organic acids or inorganic acids such as salt, p-toluenesulfonic acid, and the like.

This reaction is usually carried out in the presence of tetrabutylammonium fluoride at a temperature ranging from cold to warm.

Compound (11) can be produced by oxidizing compound (10).

This reaction can be carried out in the same manner as in the case of fermentation.

IL compound (13) can be produced by reacting compound (12) with n-octyllithium.

The reaction is carried out in a solvent such as diethyl ether, tetrahydrofuran-stopped ether, under cooling, preferably at 0.
It can be carried out at temperatures below °C.

(4S)-4 is a raw material compound that can be used in this production method.
-Hydroxy-2-cyclopenten-1-one (12)
can be produced from L-(+)-diethyl tartrate by known procedures.

Compound (14) can be produced by oxidizing compound (13).

The oxidation can be carried out by conventional methods, for example the so-called John's
es) It can be carried out by oxidation.

Compound (15) can be produced by subjecting compound (14) to a reaction for introducing a hydroxy protecting group.

This reaction can be carried out by a conventional method.

Childbirth-causing compound (16) can be produced by reacting compound (15) with a chlorinating agent.

This reaction can be carried out in a conventional manner, for example by using chlorine as the chlorinating agent.

A compound (17) can be produced by reacting a compound (16) with a compound (11) obtained by production method J.

This reaction can be carried out by a well-known reaction such as 1-aldol condensation.

Preferably, compound (16) is first activated by reacting it with lithium diisopropylamide in ether or tetrahydrofuran under cooling, and then the generated active methylene compound is reacted with compound (11) at the same temperature and in the same solvent.

Compound (1B) can be produced by dehydrating compound (17).

Dehydration is carried out by conventional methods.

Compound (19) can be produced by subjecting compound (18) to an elimination reaction of the hydroxy protecting group.

This reaction can be carried out substantially in the same manner as in "Preparation Method 1".

1. Toyotama compound (20) can be produced by acylation of compound (19).

Acylation can be carried out by a conventional method, for example, by reacting compound (19) with an acylating agent. Acylating agents used in this reaction include lower alkanoic acids or their reactive derivatives at the carboxy group.

Examples of reactive derivatives of lower alkanoic acids include acid anhydrides, active amides, active esters, acid halides, and active thioesters.

If the acylating agent is used in the free acid form, it is preferred to carry out the reaction in the presence of a condensing agent such as a carbodiimide compound or the like.

Acylation is typically carried out in a solvent such as acetone, dioxane, acetonitrile, methylene chloride, chloroform, in the presence of a base such as a trialkylamine, dialkylaniline, pyridine, etc., at temperatures ranging from cold to warm. .

1 Production Example 1 Compound [1] can be produced by subjecting compound (20) to an elimination reaction of the hydroxy protecting group.

This reaction is usually carried out by acid hydrolysis using organic or inorganic acids such as acetic acid, hydrochloric acid, p-toluenesulfodiic acid, etc. in a solvent at temperatures from room temperature to under heat. Suitable solvents include water, alcohol, acetonitrile,
Examples include N,N-dimethylformamide and the like.

The compound obtained by production method A-5 can be obtained by concentration, conversion of liquid properties, change of solvent, solvent extraction, crystallization, recrystallization,
It can be isolated and purified by methods known per se, such as fractional distillation, chromatography, etc.

The raw material compounds and target compounds of Production Method A-3 may be salts thereof.

Target compound CI] has anticancer activity and is useful as an anticancer drug.

This invention will be explained in more detail with reference to the following examples.

In the examples, Bzl means benzyl, Ac means acetyl, and K means methoxymethyl.

To a cold (-30°C) solution of titanium tetraisopropoxide (9.54 mm) in methylene chloride ([omx)] was added L-(+)-diethyl tartrate (5.50 mL).
Add the solution by syringe. After stirring for 5 minutes at -30°C, the solution was combined with a solution of (E)-7-benzyloxy-2-hepten-1-ol (4,70 g) in methylene chloride (5 ml) and IM anhydrous hydroxyperoxide in methylene chloride. Tertiary butyl (21.4ml, 21.4mmol)
The reaction mixture was stirred at -30°C for 20 hours, and
Tertiary butyl hydroxy peroxide 10% aqueous solution (80mm
) is added. The mixture is stirred at -30°C for 30 minutes and then at 20°C for 2 hours. The organic layer is diluted with methylene chloride, washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated to give a colorless oil. A cold (0°C) solution of this residue in diethyl ether (2001111) was added IN
Add aqueous sodium hydroxide solution (1 oomc). 0
After stirring for 30 minutes at °C, the organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, concentrated, and separated by silica gel column chromatography, eluting with hexane-ethyl acetate (5:4). 7-Benzyloxy-
2,3-Epoxyheptan-1-ol (4.1 g) is obtained as a colorless oil.

mouth α]D −12,9° (C=1.40.CHCL3
) NMR (CDCl2.δ): 3.4-3.6 (
3H, m), 3.65-3.9 (3Lm), 4.
50 (2H,s), 7.32 (51,br
s) H Sad encounter 1 A mixture of the target compound (15,51c) of Example 1, 2N aqueous sodium hydroxide solution (20G+d) and tertiary butanol (20011111) was stirred at 80'C for 3 days, and then hydroxylated. Make the sodium inert with carbon dioxide gas. The mixture was concentrated and ethyl acetate (300m)
Extract 5 times. The extracted organic layers were combined, dried over anhydrous magnesium sulfate, concentrated, and separated by silica gel column chromatography.
:1) to obtain (2R,3S)-7-benzyloxy-1°2.3-heptanetriol (9.5 g).

○H N,N-dimethylformamide (DMF) of the target compound of Example 2 (9.0 g) and imidazole (2.9 g)
) (40 relatives) To a medium-cold (0°C) solution is added tertiary-butyldimethylsilyl chloride (5.34 g). 5 at 0°C
After stirring for a minute, the reaction mixture was diluted with diethyl ether and
Washed sequentially with water and brine, dried over magnesium sulfate, concentrated, and separated by silica gel column chromatography, eluting with hexane-ethyl acetate (2:1), (2R,3S)-7-benzyl Oxy-1-(tert-butyldimethylsiloxy)-2,3-heptanediol (u,tg) is obtained as a colorless oil.

To a solution of the target compound of Example 3 (11.0 g) in 2,2-dimethoxypropane (100 fflll) at 0° C., quasi-camphorsulfonic acid (150 mg) is added. After stirring for 2 hours at 0°C, the reaction mixture is neutralized with saturated aqueous sodium bicarbonate solution and extracted with diethyl ether. The diethyl ether extracts were combined, sequentially washed with saturated aqueous sodium bicarbonate solution, water, and brine, dried over magnesium sulfate, and concentrated to give 2.3-(isopropylidenedioxy-7-benzyloxy)-1- (tert-butyldimethylsiloxy)heptane (12.2 g) is obtained as a colorless oil.

NMR (CDC1a, l; )' O, Q5 (6H
1s), 0.88 <9t(,s).

1.33 (3H,s), 1.40 (3H,s),
3.48 (2H, m).

3.62 (2H, m), 4.10 (2H, m),
4.50 (28,s).

6.12 (IH, d, J=5.6Hz), 7.40
(LH, d.

J = 5.6 Hz>, 7.33 (5H, br s)] dl Interchange Example 4 target compound (1,30K) tetrahydrofuran (diHF) (15ffllll) and liquid ammonia (45111Q) intermediate ( −78°C) solution,
Metallic lithium (110 mg) is added in small portions. After stirring for 45 minutes at -34 DEG C., excess powdered ammonium chloride is added to the reaction mixture and the ammonia is removed at room temperature. The residue was diluted with diethyl ether, washed with water, brine, dried over magnesium sulfate, concentrated, and separated by silica gel column chromatography, eluting with hexane-diethyl ether (1:1).2. 3-(
Impropylidenedioxy)-7-hydroxy-1-(
Tertiary butyldimethylsiloxy)heptane (92(Ls
g) is obtained.

[αco −4.89° (C=0.52.CHCl3)N
MR (CDCl2.S): o, oa (6Ls),
0.89 <9Ls).

1.34 (3H,s), 1.41 (3H,s),
3.5-3.8 (4H, m), 4.0-4.2 (
2H, m) To a solution of oxalyl chloride (669 mg) in methylene chloride (5InlI) (-78°C), dimethyl sulfoxide (517 mg) was added in methylene chloride (1+111
1) Drop the solution. The mixture was stirred at the same temperature for 3 minutes, and then a solution of the target compound of Example 5 (840 mg) in methylene chloride (5-alkanes) was added dropwise with stirring. After stirring at the same temperature for 15 minutes, triethylamine (1.07 g) was added, and stirring was continued at this temperature for an additional 10 minutes. The temperature of the mixture is allowed to rise to room temperature over 10 minutes under stirring and is partitioned between benzene and water. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure.
2.3-(impropylidenedioxy)-6-formyl-1-(tert-butyldimethylsiloxy)hexane (8
20 mg).

The target compound (800 mg) of Example 6 was dissolved in acetone (IO
IIQ) Add John's reagent (1 ml) to the mid-stage (0°C) solution.
1) is added dropwise over 5 minutes. After stirring at 0°C for 5 minutes,
Add excess 2-pentanol. After stirring for 3 minutes at 0°C, the mixture was diluted with diethyl ether-methylene chloride mixture (2
:1), washed sequentially with water and brine, dried over magnesium sulfate and concentrated.

Residue diethyl ether (15mQ) halfway (0°C)
Add excess diazomethane in diethyl ether to the solution. After stirring for 5 min at 0 °C, the mixture was concentrated and separated by silica gel column chromatography, eluting with hexane-diethyl ether (7:1) to give 5.6-
Methyl (impropylidenedioxy)-7-(tert-butyldimethylsiloxy)heptanoate (640 mg) was obtained.

NMR(CDC13,S) =0.04 (61(,
s), 0.87 (9H1s).

1.31 (3H,s), 139 (3H,s),
3.64 (3H, s).

4.06 (2H, m> Medical) d1 To a solution of the target compound of Example 7 (600 mg) in tetrahydrofuran (THF) (10111) was added a solution of tetrabutylammonium fluoride in THF (1,83111
) is added.

After stirring for 30 minutes at room temperature, the mixture was diluted with diethyl ether, washed successively with water and brine, dried over magnesium sulfate, concentrated, separated by silica gel chromatography, and purified with hexane-ethyl acetate (1: Elute with 1)! 'i, 6-(impropylidenedioxy)-
Methyl 7-hydroxyheptanoate (310+ag) is obtained as a colorless oil.

[α coD +t0.9° (C=1.28.
CHCL3) NMR (CDCIs, 8)' 1.3
3 (3H9s), 1.42 (3H1s).

' 2.35 (2H, t, J=6.5Hz), 3
．． 58 (2H, m), 3.63 (3H, s), 4
．． 12 (21,m) Using substantially the same procedure as in Example 6 and using the target compound of Example 8, methyl 5,6-(isopropylidenedioxy)-6-formylhexanoate is obtained.

NMR (CDC1s, S)' 1.40 (3H,
s), 1.58 (3H1s).

2.35 (2)1. t, J=6.8Hz), 3.6
7 (3)1. s), 4.3 (2Lm), 9.63
(IH, d, J=3.4Hz>0H and 亙五dan(4S)-4-hydroxy-2-cyclopentene-1-
(3,00 g) of tetrahydrofuran (rHF) (
40+111) A diethyl ether IN solution of n-octyllithium (70 Tsuru) is added dropwise to the intermediate (-78°C) solution over 10 minutes in an argon atmosphere. -78°
After stirring for 10 minutes at C, the mixture is partitioned between diethyl ether-methylene chloride mixture (2:1) and saturated aqueous ammonium chloride solution. The organic layer was washed sequentially with water and brine, dried over magnesium sulfate, concentrated, resolved by silica gel column chromatography, and purified with ethyl acetate.
Elute with hexane (2:1), (IR,4S)-1,
4-Dihydroxy-1-n-ctyl-2-cyclopentene (3.6 g) is obtained as a colorless oil.

[αCoD -65°9° (C=0.54.CHC
L3) NMR (CDC13,S)' 0.87 (
3H, t, J=6.0Hz>, t, 70 (ILdd
, J=14.0. 3.0Hz>, 2.40 (I
H, dd, 'J=14.0. 7.0)1z), 4
．． 63 (LH, dd, J=7.0°3.0Hz),
5.87 (2H, br s) John's reagent (5 ml) is added dropwise to a solution of the target compound (3.60 g) of Example 10 in acetone (5011111) (0°C) over 10 minutes. After stirring at 0° C. for 10 minutes, an excess amount of 2-propanol is added. After stirring at 0°C for 20°, the mixture was diluted with diethyl ether-methylene chloride (2:1), washed sequentially with water and brine, dried over magnesium sulfate, concentrated, and separated by silica gel column chromatography. , (4R)-4-hydroxy-4-n-lactyl-2 was eluted with hexane-ethyl acetate (2:1).
-Cyclopenten-1-one (2.7 g) is obtained as a colorless oil.

N,N-diisopropylethylamine (3.0 g) and chloromethyl methyl ether (1.2 g) are added to a solution of the target compound (gBomg) of Example 11 in 1,2-dichloroethane (1011111). After stirring at 40°C for 10 hours, the reaction mixture was diluted with diethyl ether, washed successively with water, saturated aqueous sodium bicarbonate solution, and saturated aqueous sodium chloride solution, dried over magnesium sulfate, concentrated, and separated by silica gel column chromatography. , eluted with hexane-ethyl acetate (8:1), (
4R)-4-methoxymethoxy-4-n-cutyl-2
-Cyclopenten-1-one (1,09 g) is obtained as a colorless oil.

[α]D-42,0°(C=2.0.CHCL3)N
MR(CDC13,l; )' 0.88 (3H1
t-1J near, 1Hz), 3.37 (3H, s),
4.66 (2Ls), 6.22 (LH, d, J=
6Hz).

7.53 (LH, d, J = 6 Hz> Dry chlorine gas was added to the target compound of Example 12 (300 mg)
The reaction was blown into a solution of dry diethyl ether (somQ) until all of the above compounds had reacted (by thin layer chromatography (TLC)), then triethylamine (10 mL) was added. After stirring at room temperature for 10 minutes, the mixture was diluted with diethyl ether, washed successively with water and saturated brine, dried over magnesium sulfate, concentrated, separated by preparative silica gel TLC, and separated by hexane-
Elution with diethyl ether (4:1) gave (4R)-4
-methoxymethoxy-4-n-octyl-2-chloro-
2-cyclopentene-1-benzene (28 mg) is obtained.

[α]D-47.4° (C=0.78.CHCl3)
NMR (CDC13,8)' 0.88 (3H,t
, J=7.1Hz), 2.58(IH,d, J=18
．． 8Hz), 2.80 (IH, d, JJg, 8Hz
).

3.35 (3H, s), 4.59 (IH, d, J
=7.6Hz>, 4.67(LH, d, J=7.6H
z>, 7.40 (IH,s)0MM Back layer ±] Lithium diisopropylamide prepared from n-butyllithium and diisopropylamine in THF (5mM
) The target compound of Example 13 (
A THF (Mitsuru) solution of 315 mg) was added dropwise over 5 minutes in an argon atmosphere. After 20 minutes at -78°C, the target compound (251 mg) of Example 9 was dissolved in THF (zmu).
Add the solution to the mixture. After stirring for 15 minutes at -78°C,
The reaction mixture is poured into a mixture of ether and saturated aqueous ammonium chloride solution, and the aqueous layer is extracted with diethyl ether. The organic layers were combined, sequentially washed with water and saturated brine, dried over magnesium sulfate, concentrated, separated by silica gel column chromatography, and eluted with hexane-ethyl acetate (4:1) to give a solution of 5.6 -(isopropylidenedioxy)-7-hydroxy7-[(2R)-2-
Methoxymethoxy-2-n-cutyl-4-chloro-5
-Methyl xoxo-3-cyclopenten-1-yl]heptasiate (200 mg) was obtained.

[α] −10,8° (C=0.5. CHCl3)
IR(CHCl3)' 3500.1725.160
5 cm-1HMR (CDCl2.δ): 0.87
(311, t, J near, 1Hz), 1.36 (3H
,s), 1.49 (3H,s), 2.58
(IH, d.

5.5Hz>, 3.35 (3H,s), 3
．． 65 (3H, s).

4.07 (LH, t, J=5.3Hz), 4.2
0 (IH, ddd.

J=9.6. 6.0. 3.5Hz), 4.45
(LH, dd, J=5.3°5.8Hz), 4.
71 (2H,s), 7.60 (IH,s)0M
M 0MM Tue 1moku>I Target compound of Example 14 (170mg), pyridine (2
, 51119) and acetic anhydride (211Q) was stirred at 70 °C for 45 h, concentrated under reduced pressure, separated by preparative silica gel TLC, and separated by hexane-diethyl ether (
2:1) to give 5.6-(impropylidenedioxy)-(7E)-7-[(2S)-2-methoxymethoxy-2-n-ctyl-4-chloro-5- Kisou 3
-cyclopenten-1-ylidene]methylheptanoate (
63 mg) are obtained as colorless waves.

[α]D+39.7°(C=1.26.CHCl3)
IR(CHCl3): 1720.1665.159
5 cm-'NMR (CHCl3.E)' 0.8
7 (3H, t, J=7.1Hz), 1.37 (3H
,s), 1.48 (3H,s), 3.37 (3
H, +), 3.64 (3H,s), 4.17 (1
1, ddd, J=9.8.5.8°3.4Hz), 4
．． 43 (2H, s), 5.12 (LH, dd.

J=10.5.5.8Hz), 6.64 (LH, d
d, J=10.5°0.4Hz), 7.37 (IH
, d, J = 0.4 Hz) 0 MM 0 MM or 1 ■ Acetic acid (2
mQ) Oyobi water (o, smn) mixture solution at 80”
(C') Stir for 1 hour and concentrate to give a colorless oil.
C) Add an excess of diazomethane in diethyl ether to the solution. After stirring for 5 min at 0 °C, the mixture was concentrated and separated by preparative silica gel TLC, eluting with hexane-diethyl ether (2N) to give (5s, 6R)-5,6
-cyhydroxy-(7E)-7-[(2S)-2-methoxymethoxy-2-n-ctyl-4-chloro-5-xo-methyl 3-cyclopenten-1-ylidencoheptanoate (29 mg).

[α KoD + 56.6 KoD = 0.58. CHCl
3) IR(CHCl3)' 3400.1720.1
660.1595 am″″INMR(CHCl3.8
): 0.87 (3H, t, J=7, IHz),
3.39 (3H, s), 3.67 (3H, s),
3.76 (IH, m), 4.49 (1) 1. d,
J=7.1Hz>, 4.53 (IH, d, J=7.
1Hz).

4.65 (IH, dd, J=6.7.4.3Hz),
6.78 (LH, dd.

J=6.3.0.5Hz), 7.35 (IH,d,
J = 0.5Hz) 0MM 0MM
, 81111) and pyridine (1 relative) mixture solution.
Heated to 0 °C for 30 min, concentrated in vacuo and separated by preparative silica gel τLC to give hexane-diethyl ether (
1:1), (5S,6R)-5゜6-diacetyl (7E)-7-[(2s)-2-methoxymethoxy-2-n-diacetyl-4-chloro-5- Oxo-3
-cyclopenten-1-ylidene]methylheptanoate (
28 mg).

[α]D+2.14° (C=0.56.CHCl3)
1R (CHCl3): 1730, 1720, 1665,
Acetic acid (2111
1) and water (0,5fflQ) mixture solution at 100%
C. for 1 hour, then 90.degree. C. for 15 hours and concentrated in vacuo to give a colorless oil. Diethyl ether of this residue (
1) Add an excess amount of a diethyl ether solution of diazomethane to the intermediate (0°C) solution. After stirring for 5 min at 0°C, the mixture was concentrated and separated by preparative silica gel τLC, eluting with hexane-diethyl ether (1:1) to give (5S
, 6R)-5,6-diacetoxy-(7E)-7-[(
2S) -Methyl-2-human axy-2-n-ctyl-4-chloro-5-oxo-3-cyclopenten-1-ylidenecoheptanoate (12 mg) is obtained as a colorless oil.

[α]D-49,2@(C=0.24.CHCl3)
IR(CHCl3): 3400.1730.171
5.1670°1590 cab-1 NMR (CDC1s, 8)' 0.86 (3H,
t, J=7.1Hz), 2.08(3H,s), 2
．． 10 (3H, s), 3.64 (3H, s),
5.06 (IH, a+), 6.20 (LH, dd,
J:9.6.2.5Hz), 6.52(IH, dd,
J=9.6.0.5Hz), 7.30 (LH, d.

J=0.5Hz)

Claims (1)

[Claims] 1) Formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^1, R^2 and R^3 are the same or different and represent lower alkyl groups) Compound. 2) (5S,6R)-5,6-diacetoxy-(7E)
-7-[(2S)-2-hydroxy-2-n-octyl-4-chloro-5-oxo-3-cyclopentene-1-
Claim 1 which is methyl ylidene]heptanoate
Compounds described in Section. 3) Formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^1, R^2 and R^3 are the same or different and mean a lower alkyl group, and R^4 means a hydroxy protecting group. A formula characterized by subjecting a compound represented by (same meaning)
A method for producing the compound shown in