JPH035472A - Optically active compound and its production - Google Patents

Abstract

NEW MATERIAL:The optically active compound of formula I [R<1> is 1-12C group selected from (alkoxy)alkyl, cycloalkyl and aralkyl having hetero atom on aromatic ring or alkyl; R<2> is H or easily eliminable protecting group selected from acyl, silyl, aralkyl and alkyloxyalkyl; * represents asymmetric carbon atom]. EXAMPLE:The compound of formula II. USE:Useful as a production raw material for optically active gamma-lactone derivative which is a key intermediate for the synthesis of prostaglandin. PREPARATION:The objective compound of formula I can be produced by reducing an optically active compound of formula III with an alkali metal selectride or a metal borohydride complex. The compound of formula III is produced by oxidizing a compound of formula V produced by the processes of e.g. the reaction of a halogen compound of formula IV with a strong base.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a prostaglandin synthesis method developed by G. 5tork et al.
akahash i.

■, awamoto, T, 5uzuki: J, A
m, Chem, Soc,, 100.

8272 (1978)) is an important intermediate in the following general formula (P) (In the above general formula (P), R1 is an alkyl group that may have an alkoxy group, a cycloalkyl group, an aromatic ring, or an alkyl group. A group having 1 to 12 carbon atoms selected from aralkyl groups having a heteroatom in the group, R2 is a hydrogen atom or an easily removable protecting group selected from acyl groups, silyl groups, aralkyl groups, and alkyloxyalkyl groups. The present invention relates to an optically active compound that is an intermediate for producing an optically active γ-lactone derivative represented by the formula (where * symbol represents an asymmetric carbon atom) and a method for producing the same.

(Prior art and problems to be solved) Regarding the production of prostaglandin, the above G, 5t
In addition to the synthesis method of Ork et al., a method starting from Corey lactone or 4-hydroxycyclobentenone has been put into practical use, but this method requires optical resolution or asymmetric hydrolysis by microorganisms to obtain the optically active material. It is necessary to go through the following steps, and there are many problems in steric control at the stage of introducing α and ω side chains based on these steps. From this point of view, the method of synthesizing prostaglandins using the optically active γ-lactone derivative of general formula (P) as a key intermediate, developed by G. 5tork et al., can be said to be an excellent method. However, the problem with this method lies in how economically the compound of general formula (P), which serves as a key intermediate, can be produced.

(Means for Solving the Problems) As a result of intensive investigation to solve the above problems, the present inventors have discovered that the compound represented by the above general formula (P), which is a key intermediate, can be produced more easily and efficiently than before. The present invention provides an intermediate obtained in the process of this production and a method for producing the same.

The present invention is based on the following general formula (A> (In the above general formula (A>), R1 is an aralkyl group having a petero atom in an aromatic ring or alkyl group, a cycloalkyl group, an alkyl group that may have an alkoxy group, The selected group having 1 to 12 carbon atoms, R2 represents a hydrogen atom or an easily removable protecting group selected from an acyl group, a silyl group, an aralkyl group, and an alkyloxyalkyl group, and the symbol * represents an asymmetric (representing a carbon atom) and its production method.

Specific examples of R1 in the above general formula (A) are methyl, ethyl, propyl, and isopropyl.

Butyl, isobutyl, pentyl, isopentyl.

22-dimethylpentyl, r\xyl, 2-hexyl,
heptyl, 2-heptyl, octyl, 2-octyl, nonyl, 2-nonyl, decyl, 2-decyl, undecyl,
2-Undecyl, dodecyl.

2-ethoxy-1,1-dimethylethyl, 5-methoxy-1-methylpentyl, cyclopentyl.

3-Ethylcyclopentyl, cyclohexyl.

Straight chain or branched alkyl group or cycloalkyl group optionally having an alkoxy substituent such as 2-methylcyclohexyl, 4-n-propylcyclohexyl, phenyloxymethyl, 3-trifluoromethylphenyloxymethyl, 2 -Chlorothiophen-5-yloxymethyl, furan-2-yl-2-ethyl, and other aralkyl groups having a petero atom in an aromatic ring or an alkyl group.

Specific examples of R2 other than hydrogen atoms in general formula (A) include acyl groups such as benzoyl, acetyl, and p-phenylbenzoyl; silyl groups such as t-butylmethylsilyl, trimethylsilyl, and t-butyldiphenylsilyl; benzyl; , aralkyl groups such as 4-nitrophenylmethyl, and fluoroxyalkyl groups such as tetrahydropyranyl and 1-ethoxyethyl.

Prostaglandins are compounds with extremely strong physiological activity that are produced by chemical conversion of higher unsaturated fatty acids such as arachidonic acid by prostaglandin synthase in vivo, and have the following structure.

OH OH GF OH GE In natural prostaglandins, R1 is n -C5H1
1-1R is (CH2)e C0OH or CH2CH=C
It is known that in I-((CH2)3C0OH, it is important for the R1 substituent to be lipophilic for the expression of physiological activity. As R1, an alkyl group, a cycloalkyl group, or an aralkyl group having 4 to 10 carbon atoms is effective, such as pendel, isopentyl, 2,2-dimethylpendel, hexyl, 2-hexyl, heptyl, 2-
Ethoxy-1,1-dimethylethyl, 5-methoxy-1
-Alkyl groups such as methylpentyl, cyclopentyl,
Cycloalkyl groups such as 3-ethylcyclopentyl and 4-propylcyclohexyl, phenyloxymethyl,
It has been revealed that aralkyl groups such as 3-trifluoromethylphenyloxymethyl, 2-chlorothiophen-5-yloxymethyl, and furan-2-yl-2-ethyl exhibit particularly strong physiological activity. The compounds of the present invention are useful as raw materials into which substituents including these organic groups can be introduced.

The method for synthesizing the edinyl alcohol derivative represented by the above general formula (A>) of the present invention will be explained below according to synthetic route (2). In the following, X represents a halogen atom and M represents an alkali metal.

(2') (4) (1) (2) (B) In the above reaction, the halogen compound (1) is reacted with a strong base such as n-butyllithium, t-butyllithium, methyllithium, lithium diisopropylamide, etc. An acetylene compound (2) is obtained, and then an alkali metal acetylide (2') is obtained by using these strong bases. Compound (4) is obtained by reacting optically active aldehyde (3) with this.

The alkali metal acetylide (2') may be prepared by neutralizing the acetylene compound (2) as described above and reacting it again with a strong base, but more simply, the halogen compound (1) can be prepared by Alkali metal acetylides obtained by reacting with twice or more of a strong base can be used as they are.

This alkali metal acetylide and optically active aldehyde <3
) is preferably carried out at a low temperature of -78°C to 0°C.

The reaction to obtain compound (4) is tetrahydrofuran.

It can be carried out in an inert solvent such as diisopropyl ether or toluene at a temperature range of -78°C to room temperature. Compound (4) obtained by this reaction is a mixture of erythro form (A-1> and threo form (A-2>) as shown by the chemical formula below.

OH From this mixture, erythro form (A-1>) or threo form (A-1>
-2) can be obtained selectively by separation using column separation or the like, but each optical isomer can be easily and more selectively produced by a chemical method as described below. Add an oxidizing agent to this compound (4), such as CrO3-pyridine, dimethyl sulfoxide (DM
The ethynyl ketone derivative of compound <8> can be obtained by oxidation using SO)-acid halide or the like.

The reaction for synthesizing the optically active ethynyl alcohol derivative (A>, which is the target compound of the present invention) from this compound (B) is as follows:
The reaction conditions differ depending on whether the ethynyl alcohol derivative (A> shown in the above chemical formula) is the erythro form (A-'I) or the threo form (A-2>). A-1>, the compound (B) is a borohydride zinc complex (Zn (Bt-1
a) When the threo form (A-2) is desired, the ethynyl alcohol derivative (A-2) of the desired configuration can be obtained with good selectivity by reduction with an alkali metal selectride, such as potassium selectride. ＞
can be obtained.

Halogen compound which is the starting material in the above reaction 1)
can be easily synthesized by reacting optically active 2,3-0-isopropylidene glyceraldehyde obtained from D-mannitol or optically active glycidol by a known method with triphenylphosphine and tetrahalomethane.

Further, the above-mentioned optically active aldehyde (3) can be synthesized according to the following synthetic route (2). In the following, R1
, R2 and * signs are R1, R2 and * of general formula (△)
, and X and Y each independently represent a hydroxyl group or an acyl group.

Represents a group or atom selected from a sulfoxy group and a halogen atom.

(C) (a) (d) (b) (e) (f) (3) The above optically active mannitol is reacted with acetone in the presence of an acid catalyst to form triacetonide (a>), which is partially hydrated with hydrous acetic acid. The tetraol (b) is decomposed, and its -class hydroxyl group and secondary hydroxyl group are selectively converted into acyl groups and sulfoxy groups with triphenylphosphine-CCf'4.acid halide-pyridine, pyridine-methanesulfonyl chloride, etc. Acetonide (C) is obtained by converting part or all of it with a group or a halogen atom.Then, this acetonide (C) is converted into acetonide (C).
After converting C) to diepoxide (d>) with a base, R3MgB
r, R3MgBr-Cu2 (CN)2゜R3Li(
However, R3 represents a group with one less carbon number than R1)
or lithium hydride, introduces R1 group with cumaluminum, etc., and further reacts the hydroxyl group with R2X'(X' is a halogen atom or sulfoxy group) to form acetonide (e), which is hydrolyzed to form diol (f). After that, Pb (O
The desired optically active aldehyde (3) can be obtained by oxidation with Ac) 4, N, aIOa, etc.

The optically active ethynyl alcohol derivative represented by the general formula (A>), which is the object of the present invention and is the objective product of the present invention, is converted into a γ-unsaturated carboxylic acid derivative, which is the compound (6), according to the following synthetic route Compound (P), which is a key intermediate in grandin synthesis, can be converted into a γ-lactone derivative.In the following, R4 represents a low-strength alkyl group having 1 to 5 carbon atoms.

<A> (5) (6) (P) In the above reaction, the ethynyl alcohol derivative (A) is led to the allyl alcohol derivative (5) by reducing the triple bond to a trans double bond with lithium aluminum hydride or the like. This reaction can be carried out in an inert solvent such as tetrahydrofuran or dioxane at a temperature of 40 to 80°C. The allyl alcohol derivative (5) is converted into the γ-unsaturated carboxylic acid derivative (6) by subjecting it to a heating reaction with trialkyl orthoacetate in the presence of an acid catalyst to perform a Johnson-Claisen rearrangement reaction. The trialkyl orthoacetate used is trimethyl orthoacetate.

Triethyl orthoacetate, tripropyl orthoacetate.

Examples include tributyl orthoacetate, triheptyl orthoacetate, etc., and the reaction is carried out at a temperature of 130 to 180'C in a solvent such as toluene, xylene, mesitylene, etc. using 2 to 10 times equivalent amount to the allyl alcohol derivative (5). be exposed. As acid catalysts, Lewis acids, Lewis acid complexes (for example, BF
Organic acids such as 3.(C2H5) 20) and heptanoic acid are used. When the acetonide of the γ-unsaturated carboxylic LX conductor (6) thus obtained is ring-opened with an acid catalyst and intramolecularly lactonized, it is expressed by the general formula (P), which is a key intermediate in prostaglandin synthesis. Optical activity γ
-Lactone derivatives are obtained. Hydrolysis of acetonide in this reaction can be carried out using hydrous organic acids, alcohols such as methanol or ethanol, mineral acids in solvents such as acetone or dioxane, BF3/ether complexes, Cu5Oa, Zn5O, etc.
Using a Lewis acid or a Lewis acid complex such as a, room temperature to 80'
It can be carried out at a temperature of C.

The compound of general formula (P) thus obtained can be converted into prostaglandin (the above-mentioned PGE, PGF) according to the prostaglandin synthesis method of G. Tark et al. Therefore, in the present invention, the optically active compound of the general formula (A>) has the general formula (A> in which both the 2nd and 6th positions are S, and the 5th position is R. is required.

The present invention will be explained below with reference to Examples.

(Example) Example <Synthesis of compound (a)> 45 g of D-mannitol was vigorously stirred in 1.12 g of acetone and 1 d of concentrated hydrochloric acid under extremely humid conditions for 3 days, and then 50 fJ of potassium carbonate was added, Stir for days. The solid matter was removed by suction filtration, the solvent in the filtrate was evaporated under reduced pressure, water was added to the resulting residue, and the precipitated crystals were collected by suction filtration to obtain 45 Cl of the crude product. After heating and dissolving this in 20 rIdl of ethanol, it was filtered, and the filtrate was cooled to room temperature and the precipitated crystals were traced, and the optical activity (2R,
3R,4R,5R) triacetonide (a) 37
．． 3 g (yield 50%) was obtained.

18NMR (Cα4) δ: 1.40 (6H,S, CH3X2 >1
．． 43 (12H,S, CH3X4)3.7
~4.4 (8H,m,CH2,CH)〈Compound (b
) Synthesis of triacetonide (a) 150 (0,0
After stirring for 3.5 hours at 40°C in rough 0% vinegar [507, it was immediately concentrated under reduced pressure at 40°C, and acetone was added to the residue to crystallize D-mannitol (0,72
(J) was filtered off, and acetone was distilled off from the filtrate under reduced pressure to obtain a syrup-like product. This was recrystallized with 50m of benzene to give an optical activity (2R, 3R, 4R) shown by the chemical formula below.
, 5R) tetraol (b) 8.8(J (yield 80
%) was obtained.

1HNMR (C20) δ: 1.38 < 6H,S, CH3X2)
3.3-4.2 (8H, m, CH2, CH) Synthesis of compounds (C) and (d)> Tetrol (b) obtained above 15.3 g<0.
069m0+>, anhydrous pyridine 55m (0,68m
ol), CH2Cf125 (70°) in a solution of
Benzoyl chloride (0,138m01>,
A mixed solution of anhydrous CH2 (J25m) was added dropwise over 15 minutes, and after the dropwise addition, the mixture was further stirred at -30'C for 1 hour and at room temperature for 10 hours. After confirming the completion of the reaction by thin layer chromatography, the solvent was distilled off under reduced pressure. did.

To this residue, 11.2 ml of methanesulfonyl chloride (0
, 144 mof) was added over 20 minutes at 0°C, and the suspension was further stirred at room temperature for 3 days. Completion of the reaction was confirmed by thin layer chromatography, and 100 d of a mixed solvent of ethyl ether:hexane = 7:3 (volume) was added to the reaction mixture, and this yellow suspension was filtered through Celite-545.
The solvent was removed under reduced pressure. The obtained brown residue was dissolved in CH202
The mixture was diluted with 2 and acidified with concentrated hydrochloric acid, and then extracted three times with CH2α2. The extract was washed successively with saturated aqueous sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain optically active compounds (2R, 3R,
4R.

42 g of acetonide (c), a brown semi-solid substance of 5R> body, was filtered through Celite-545, the filtrate was concentrated under reduced pressure at 40°C, and 3M of a mixed solvent of ethyl ether:hexane = 7:3 (each digit) was added. The mixture was filtered again through Celite-545, the solvent was distilled off under reduced pressure at 40°C, and a crude product was obtained by distillation under reduced pressure. This is further recrystallized from benzene to obtain pure optical activity (2S, 3R, 4
R, 53) diepoxide (d>2.71 yield 21%
) was obtained.

(C) (However, MS represents a methylsulfoxy group, and pH represents an engineering group) The above acetonide (C) 42(], K2 GO32
After stirring 0 g in 130 ml of methanol for 15 hours,
Reaction solution 'HNMR (CDCb) δ: 1.39 (6H.

2.6~2.9　＜　48゜ 2.95-3.12 (2H.

3.7-3.95 (2H.

CH3X2 ) CH2X2 ) CH) CH) <Synthesis of compounds (e) and (f)> A separately prepared concentration of 1.47 was added to a mixture of 320 mg of Cu2 (CN)2 and 100 d of anhydrous tetrahydrofuran.
64 m (94 m mol) of an ether solution of n-butylmagnesium bromide was sipped at 0°C over 5 minutes. After roughly stirring for 5 minutes, the dieboxide (d) obtained above was mixed with 6.48 m (94 m mol) of n-butylmagnesium bromide. A solution of anhydrous tetrahydrofuran 507 was added dropwise at 0°C over 10 minutes with stirring, and the mixture was roughly stirred for 1 hour. After confirming the completion of the reaction by thin layer chromatography, the solution was decomposed with NHaα and saturated saline, and 3
After stirring for 0 minutes, the mixture was extracted three times with ethyl ether, and the ether layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine, dried over anhydrous magnesium chloride, filtered, and the solvent of the filtrate was distilled off. The optical activity (68,7R
, 8R, 9S) crude diol (e-1>) was obtained.

The crude diol (e-1> obtained above was dissolved in 30 d of anhydrous tetrahydrofuran, and 0.4 d of sodium hydride was added to the solution.
100 d of anhydrous tetrahydrofuran (1.07 mmol) was added dropwise to the mixture over 15 minutes under reflux, and the mixture was roughly stirred and refluxed for 1 hour, and then cooled to 0°C. DC-1 to this suspension
8-crown ether-6132 mg and benzyl bromide 9
．． 3 m (78 mmol) was added with O'C and stirred and refluxed for 4 hours. The reaction solution was concentrated under reduced pressure, decomposed with 1N hydrochloric acid, extracted three times with hexane, and the extract was diluted with saturated aqueous sodium bicarbonate and saturated brine. After washing and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain the optical activity (6
3,7R,8R,9S) acetonide (e-2>) was obtained.

(However, 3n represents a benzyl group) The above acetonide (e-2>
After heating and stirring at 0'C for 10 hours, the solvent was distilled off under reduced pressure.
Next, it was extracted with ethyl ether, the extract was washed with an aqueous solution of caustic soda, and the aqueous layer was roughly extracted with ethyl ether.
These ether layers were combined, washed successively with 1N hydrochloric acid, saturated sodium bicarbonate solution, and brine, and dried over anhydrous magnesium sulfate.

After distilling off the solvent, it was purified by silica gel column chromatography, eluted with ethyl ether:hexane = 1:4 (volume)), and the optical activity represented by the following chemical formula (63,7R,
8R,93) diol (f) 8.66 g (compound (
d) with a yield of 55%).

(However, Bn represents a benzyl group) 'HNMR (CDCI23) δ: O, 138 (6H, br, CH3X2 >1.0~
1.8 (16H, m, CH2X8) 3.4~3
．． 7 (4H, m, CH) 4.46 (2H,
d, J=10.81(z, 0H)4.62
(2H, d, J=10.8Hz, CH)7.30
(IOH,S, CaHs)〈Compound (3)
Synthesis> 200 mg of the diol (f) obtained above.

260 mg of lead tetraacetate was added to 360 mg of K2CO and 4.5 d of anhydrous benzene at 4°C, and the mixture was stirred for 3 minutes. After the reaction is complete, add 1G0r111 of hexane and add Celite-54.
5, the filtrate was washed with saturated aqueous sodium bicarbonate, the aqueous layer was extracted twice with hexane, the hexane layers were combined, washed with saturated brine, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, it was purified by silica gel column chromatography (ethyl ether:hexane=1:2 (volume)) to obtain (
S)-2-benzyloxyheptanal (3) 16
0 mg (yield 80%) was obtained.

(However, Bn represents a benzyl group) 'HNMR (CDCJlx) δ: 0.87 (3H, t, J = 5.8Hz
.

CH3> 1.0~1.8 (8H,'m, CH2) 3.73
(IH, dt, J = 2.2Hz.

6.2H1,CH) 4.51 (IH,d, J=11.6NZ,
CH) 4.65 (1t-f, d, J=11
．． 6Hz, CH)7.34 (5H,S,Ca
Hs) 9.64 (IH, d, J= 2.2
Hz) <Synthesis of compound (4)> (S)-dibromide 4.8 (1(16,
8 mmol) of anhydrous tetrahydrofuran (100 m)
Cool to 8°C and add 16.4 m of butyllithium-hexane solution with a concentration of 1.62 mol (26.6 m
mol> was added dropwise over 10 minutes, stirred for roughly 1 hour at -78°C and 1 hour at air temperature to convert it into optically active lithium acetylide (2'), which was then cooled to -78°C to obtain the above-mentioned product. (Si2-benzyloxyheptanal (3)
2.41 g (4.4 mmol) of anhydrous tetrahydrofuran (20 ml) was added dropwise, and after further stirring for 30 minutes, the mixture was decomposed with an aqueous ammonium chloride solution, extracted three times with ethyl ether, washed with saturated brine, and then dried over anhydrous magnesium sulfate. did. The solvent was distilled off under reduced pressure, and silica gel column chromatography (ethyl ether:hexane = 1:3 (
volume)) to produce (2
3.63) compound 3.81q is 19 (yield 64%)
). This one is erythro body Nidoreo body-64: 36
(weight) mixture.

(However, Bn represents a benzyl group) <Synthesis of compound (B)> 680 mg of anhydrous dimethyl sulfoxide (8.7 m mo
15 m of anhydrous methylene chloride! Add 0.38 m (4°4 mmol) of oxalyl dichloride to the solution at -70°C for 50 minutes.
The mixture was added dropwise over a period of minutes and stirred roughly for 10 minutes at the same temperature.

To this, the erythro body obtained above and the nidoleo body = 64:36
Compound (4) 1.00 g (2.9 mmol) of anhydrous methylene chloride 4d was added dropwise and stirred at -70'C for 9 minutes. To this was added 2.0 ml of anhydrous triethylamine (14 m
mol> was added dropwise and the temperature was gradually returned to air, then hexane was added and the mixture was filtered through Celite-545, and the filtrate was washed with 1N hydrochloric acid. The aqueous layer was extracted three times with methylene chloride, and the extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and subjected to silica gel column chromatography (ethyl ether:hexane=1:10 (volume)).
) to obtain 550 mq of the (23.63> ethynyl ketone derivative (B) shown in the following chemical formula (yield: 5
5%).

(However, Bn represents a benzyl group) IHNMR<CDα3) δ: 0.86 (3H, br t, J= 7
．． 2Hz.

CH3) 1.0-1.9 (8H, m, CH2) 1.38
(3H,S,CH3)1.47 (3H,
S, CH3) It, 02 (IH, dd, J
= 5.6H2゜8.24H2, CH) 418 (IH, dd, J = 6.4Hz.

8.241-fz, CH) 4.42 (IH, d, J=11.5Hz,
CH) 4.70 (IH, d, J=11.5
H2, CH) 4.86 (IH, dd, J=
5.6Hz.

6.4H2,CH) 7.31 (5H,S, C6H5)IRνm
ax (neat) 695, 735. 835.1060.1220.1
320°1370, 1380.1450.1B75.2
200.2860゜2920, 3020 cm-1 <Synthesis of compound (A>)> The ethynyl ketone derivative (B) of the (23.63) form obtained above was poured into 550 mg (1.6 m mot) of anhydrous ether 16d at -30°C. 9.6 m of zinc borohydride-ethyl ether solution with a concentration of 0.26 mol (2.5 m
mol) was added dropwise over 5 minutes under a nitrogen atmosphere, and the mixture was roughly stirred for 30 minutes. After the reaction was completed, water and 20 ml of 0.5N hydrochloric acid were added, and the mixture was stirred at 0°C for 30 minutes. The aqueous layer was extracted three times with ethyl ether, and the extract was washed successively with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and subjected to silica gel column chromatography (ethyl ether:hexane=1=3 (volume))
It is purified by the following chemical formula (23.5R, 63)
349 mO of an ethynyl alcohol derivative (A) (erythro-nidoreo-isomer = 90:10 (weight)) was obtained (yield 63%).

(However, Bn represents a benzyl group) 1HNMR (CDα3) δ: 0.87 (3H, br t, J= 7
．． 2Hz.

CH3) 1.0-1.8 (8H, m, CH2) 1.36
(3H,S,CH3)1.45
(3H,S,CH3>3.49 (IH,dt
, J = 3.8Hz.

6.4H2, CH) 3.88 (1H, dd, J= 6.4H2゜7
．． 7H2, CH) 4゜12 (IH, dd, J= 6.4Hz
.

7.7NZ, CH) 4.4-4.7 (IH, m, J = 1.5Hz.

3.8Hz, CH) 4.59 (2H, S, CH2) 4.69
(IH, ddd, J= 1.5tlz.

6.4H2,6,4H2,CH) 7.30 (5H,S, C6H5)13CNM
R(CDC13) δ: 13.98. 22.54. 25.27.
25°96. 26.22゜30.06. 31.85
．． 64.1B, 65.57. 69.94°72
．． 49. f31.50. 83.70. 84.0
0.100.31゜127.83.128.40.13
8.21 Using the above-obtained ethynyl alcohol derivative (A), which is the object of the present invention, the optical compound represented by the above-described (P), which is a key intermediate for prostaglandin synthesis, according to the following example. An active T-lactone derivative was synthesized.

<Synthesis of compound (5)> 105 mg (0,30 m mo
A 2d solution of anhydrous tetrahydrofuran of
> of anhydrous tetrahydrofuran 5I7112 at 0°C, and the mixture was stirred and refluxed for 18 minutes. After the reaction was completed, ethyl acetate, ethanol, water, and 0.1N hydrochloric acid were sequentially added for decomposition, and the aqueous layer was extracted twice with ethyl ether. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and silica gel column chromatography (
Ethyl ether:hexane=1:3 (volume)) to obtain the (23.5R,63) allyl alcohol derivative (5) 80.1 mC1 represented by the following chemical formula (yield: 76%).

(However, Bn represents a benzyl group) 1HNMR (CDα3) δ: 0.86 (3H, t, J = 5.4.H
2゜CH3) 1.38 (3H, S, CH3) 1.40
(3H, S, CH3>1.04~1.8 (8H,
m, CH2) 3.2-3.5 (IH, m, CH)
3.52 (IH, dd, J= 7.7Hz.

7.7tiZ, CH) 4.08 (1H, dd, J= 6.4H2°8, OH2, CH) +3ONMR (CDα3) δ: 14.02. 22.61. 25.46.
25.92. 26.72°29.42. 31.93
．． 69.44. 72.22. 72.5B.

'82.18.127.72.127.79.128.
40.129.89゜132.47.140.60 <Synthesis of compound 6)> Allyl alcohol derivative (5) of the (23.5R,68) form obtained in 17 above 80.1m(] (00,23mf
f1ol>, trinible orthoacedate 0.15
m1 (0.82 mmol) and heptanoic acid as a catalyst were heated and reacted in xylene 3d at 160° C. for 20 minutes, the xylene and the produced ethanol were distilled off under reduced pressure, and after the reaction was completed, the mixture was decomposed with saturated sodium bicarbonate water. The aqueous layer was extracted twice with ethyl ether, and the extract was washed with saturated brine and dried over anhydrous magnesium sulfate. After removing the solution under reduced pressure,
It was purified by silica gel column chromatography (ethyl ether:hexane = 1:, 10 (volume)) to obtain ethyl γ-unsaturated carboxylate (6) of the following chemical formula (1'S, 33.63>) 65. 6 m(l) was obtained (yield 68%).

(6) (However, Bn represents a benzyl group) IHNMR (CDα3) δ: 0.8 & (3H, br t, J= 7
．． 2Hz.

CH3) 1.0-1.8 (8H, m, CH2) 1.33
, (3H,S,CH3)1.44 (3H
,S,CH3)2.40 (IH,dd
, J=9.0tlz.

14.7Hz, Cf-1> 2.50 (IH, dd, J= 5.1112°14.7H2, CH) 2.6~3.0 (It-(, m, CH) 3.5~
3.8 (2 days, m, CH2) 3.9-4.3
(2H,m,CHX2)4.09 (
2H, q, J= 7.2H2゜CH20) 4.31 (1)-1, d, J=I
L7tlz.

CH208H5> 4.55 (IH, d, J = 11.7Hz.

CH2C6H5) 5.2 ~ 5.7 (2H, m, =CH-)7
．． 27 (5H, S, C6 to 15
)13ONMR (CDC13) δ: 14.00. 14.25. 22.59.
25.03. 2B, 30°31.77, 35.72
．． 36.50. 41.77, 60.32°66.
81. 69.79. 77.30. 79.74.1
09.08°127.28.127.72.128.2
0.130.84.134.45゜139.00.17
1.79 <Synthesis of compound (P)> 65 mg (0.16 m mo
l>, methanol 5r1111 water 1.25m and Cu
SO4.5820186 mg (0.75 mmol) was stirred and refluxed for 13 hours. After the reaction was completed, ethyl ether was added and the mixture was filtered through Celite-545. The filtrate was washed with saturated brine and dried over anhydrous magnesium sulfate. After removing the solvent under reduced pressure, silica gel column chromatography (
Ethyl acetate:hexadi=1:5 (volume)
-Lactone derivative (p) 35.5...Q was obtained (yield 69
%).

Bn (However, Bn represents a benzyl group) 't-INMR (CD (J3) δ: 0.88 (3H, br t, J = 7
．． 2H2°CH3) 1.0 to 1.8 (8H, m, CH2)3.
72-3.9 (5H, m, CH2, Cl-1
>4.4 ~4.7 (IH, m, CI-(>4
．． 36 (IH, d, J=11.7H2゜C
H2) 4.51 (IH, d, J=11.7Hz.

CH2) 5.55 (IH, dd, J= 6.7H
2゜15.4H2,=CH) 5.68 (IH, dd, J= 7.7H2゜1
5.4H2,=CH) 7.29 ('5H,S, C8H5)13C
NMR (CDQ!3) δ: 14.00. 22.57. 24.98.
31.89. 34.94°41.02. 62.27
．． 70.42. 79.50. 82.60°127
．． 52.127.62.128.23.135.62.
138.63゜176.48 (Effects of the Invention) The optically active compound of the present invention is an important compound as a raw material for the production of optically active γ-lactone derivatives, which are key intermediates in prostaglandin synthesis. By using this compound, the key intermediate can be produced relatively easily and efficiently.

Claims (1)

[Scope of Claims] (1) An optically active compound represented by the following general formula (A). ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (A) In the above general formula (A), R^1 is an alkyl group that may have an alkoxy group, a cycloalkyl group, an aromatic ring, or a hetero atom in the alkyl group. a group having 1 to 12 carbon atoms selected from aralkyl groups, R^2 represents a hydrogen atom or an easily removable protecting group selected from acyl groups, silyl groups, aralkyl groups and alkyloxyalkyl groups, The symbol * represents an asymmetric carbon atom. (2) The optically active compound according to claim 1, wherein R^1 in general formula (A) is an alkyl group having 4 to 10 carbon atoms. (3) The optically active compound according to claim 2, wherein the alkyl group is a pentyl group. (4) The optically active compound according to any one of claims 1 to 3, wherein R^2 in general formula (A) is an aralkyl group. (5) The optically active compound according to claim 4, wherein the aralkyl group is a benzyl group. (6) The compound of general formula (A) has optical activity (2S, 5R,
6S) compound according to any one of claims 1 to 5. (7) The following general formula (A) ▲ Numerical formulas, chemical formulas, tables, etc. are included ▼ (A) (In the above general formula (A), R^1 is an alkyl group that may have an alkoxy group, a cycloalkyl group and a group having 1 to 12 carbon atoms selected from aralkyl groups having a heteroatom in an aromatic ring or an alkyl group, R^2 is a hydrogen atom or a group selected from an acyl group, a silyl group, an aralkyl group, and an alkyloxyalkyl group. When producing an optically active compound represented by the formula (representing a protective group that can be removed by
B) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(B) (In the above general formula (B), the signs of R^1, R^2 and * are the same as R^1, R^2 and * of general formula (A). 1. A method for producing an optically active compound, which comprises reducing an optically active compound represented by the following symbol * with an alkali metal selectride or a borohydride metal complex. (8) The method according to claim 7, wherein R^1 in general formula (A) is an alkyl group having 4 to 10 carbon atoms. (9) The method according to claim 8, wherein the alkyl group is a pentyl group. (10) The method according to any one of claims 7 to 9, wherein R^2 in general formula (A) is an aralkyl group. (11) The method according to claim 10, wherein the aralkyl group is a benzyl group. (12) The compound of general formula (A) has optical activity (2S, 5R
, 6S) is the production method according to any one of claims 7 to 11.