JPS6360980A - Production of (r,z)-5-tetradecene-4-olide - Google Patents

Abstract

PURPOSE:To readily obtain the titled compound as a sex pheromone of Japanese beetle in high purity, by subjecting trihydroxy-(methoxyethylidene)-tetradecane- olide to thermal decomposition in the presence of an acid catalyst. CONSTITUTION:(4R,5S,6R)-4,5,6-Trihydroxy-5, 6-O-(1-methoxyethylidene)-tetrade cane-4-olide expressed by formula I is subjected to thermal decomposition in the presence of an acid catalyst (preferably acetic anhydride) preferably in an amount of 5-20wt%, e.g. at 120-150 deg.C for 2-4hr, to provide the aimed compound expressed by formula II. The compound expressed by formula I can be produced from a compound expressed by formula III which is a standing material.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention is directed to
The present invention relates to a method for producing (R,Z)-5-tetradecen-4-olide, which is known as the sex pheromone of tlePopillia japonica).

More specifically, the present invention relates to (R , z)-5-tetradecen-4-olide.

(Prior Art) Japanese hggtlt is a coleopteran insect and is a pest that causes great damage to trees, agricultural crops, grass, and the like. It has already been revealed that the secretions of virgin females of this insect strongly attract males, and that this attractant is (RlZ)-5-tetradecen-4-olide specified by the above formula (1). In addition, the racemate of the above formula (1) does not exhibit male attracting activity, and furthermore, the racemate of the above formula (1)
The (+)-isomer of 1) has also been found to inhibit male attracting activity.

Conventionally, regarding the synthesis method of the above formula (11 compound), for example, the method shown in the reaction process diagram below is known (Agric
, Biol, Chem,, Tough (11) 25
95-2598 (1983).

This proposed synthesis method is based on the formula (α) in the process diagram above.
This is a method for synthesizing a compound of formula (6) using 1-decyne as a starting material and using l·ξ as a key step, particularly asymmetric reduction of the compound of formula (d) above. According to this proposal, it is disclosed that the yield of the compound of formula (1) from the compound of formula (α) is 22%.

(Problems to be Solved by the Invention) In the above conventional proposal, the optical purity of the compound of formula (=) obtained by asymmetric reduction of the compound of formula (d) is 79 to 8.
In order to obtain the above-mentioned compound 2 with a high purity of 5%, complicated operations such as optical resolution of the above-mentioned formula (a) compound are required. In addition, in the step of obtaining the compound of formula (1) by catalytic reduction of the compound of formula (1),
z) In addition to (E) the generation of one body is difficult to avoid, and
A separation operation is necessary. Furthermore, optical resolution reagents and asymmetric reduction methods are expensive and unsuitable for industrial production, and there are many drawbacks and difficulties.

(Means for Solving the Problems) The present inventors have conducted extensive research in order to solve the disadvantages and drawbacks of the above-mentioned conventional proposals.

As a result, by using monoarapinose or D-glucose, which is easily available on the market, as an asymmetric source, the above formula o)(-), (Z
) It has been discovered that -5-tetradecen-4-olide can be easily and inexpensively synthesized with industrial advantage.

That is, according to the research of the present inventors, the following formula (8), which is easily available on the market and can be easily synthesized from monoacybinose or D-glucose by known means, where R represents a pentyl group, (-)-0-Benzu-5,4-0-inglobylidene-α, D-arabinose or D-glucose represented by the formula (-)-0-benzene-5. Become (Z)
-The following formula (7) having an α, β-unsaturated site and a 2', 5'-inoglobylidene glycerol group in the side chain, where R is as defined above, and R' is a methyl group or an ethyl group. It has been found that by using a compound represented by as an intermediate, a compound of formula (1) having natural optical activity and (z) an integral side chain double bond can be easily synthesized with high purity. Ta.

Therefore, the object of the present invention is to solve the above formula (1) (R, Z )
In the synthesis of -5-tetradecen-4-olide, the synthesis of the compound of formula (8) is a key step (Kgyste
(p)) To provide a new method for producing the compound of formula (1), which does not involve racemization during the reaction process and can easily deal with the problem of evimerization by adding a plurality of asymmetric carbon atoms. .

The above objects and many other objects and advantages of the present invention will become more apparent from the following description.

The process diagram of the synthesis of the above formula (tl (R,Z)-5-nato-2-decene-4-oli) of the present invention can be shown as follows.

The method for synthesizing the compound of formula (1) of the present invention will be described in more detail below according to the process diagram above.

In the method for synthesizing the compound of formula (1) of the present invention,
The compound of formula (8) as a starting material can be easily synthesized from D-arabinose or D-glucose by a known method (J, Chgm.

Sac,, Chgm, Cornrnum,, 747 (
1982).

In order to synthesize the compound of formula (7) from the compound of formula (8), the compound of formula (8) is mixed with carboalkoxymethylenetriphenylphosphorane in an organic solvent, for example.
.

(C,H,), P=CIICOR can be easily synthesized in good yield by conducting a Witstec reaction.

The reaction temperature and reaction time of this reaction can be selected as appropriate, but for example, a temperature range of about 5@ to about 40°C, more preferably a temperature range of about 10°C to about 25°C is exemplified. can do. Further, the reaction time can range, for example, from about 5 hours to about 5 hours. Examples of the organic solvent used in the reaction include dichloromethane, tetrahydrofuran, sochloroethane, and N.

Preferred examples include N-dimethylformamide and acetonitrile. There are no particular restrictions on the amount of these organic solvents to be used, and they can be selected as appropriate.
For example, for the compound of formula (8) above, preferably about 10 to
This can be done with a usage amount of about 20% by weight. Also, as the amount of force used for this reaction, for example, formula (8)
A preferable example is a range of about 1 to 3 moles based on the compound.

After the reaction is completed, the compound of formula (7) can be obtained in good yield and high purity by post-treatment according to a conventional method.

In order to synthesize the above formula (6) compound from the above formula (7) compound that can be obtained as described above, for example, the formula (
It can be easily synthesized by subjecting the compound to an oxidation reaction in an organic solvent in the presence of an oxidizing agent. The temperature of this oxidation reaction can be selected as appropriate, but preferably ranges from about 10°C to about 50°C. Further, the reaction time can be suitably selected to carry out the oxidation reaction, and for example, the time can preferably be set in a range of about 5 to about 8 hours. Preferred examples of the oxidizing agent used in the reaction include bilisonium chlorochromate, DMSO-acetic anhydride, and DMSO-oxalyl chloride. The amount of the oxidizing agent to be used is, for example, about 1.5 to about 5 moles per mole of the compound of formula (7). Specific examples of preferable organic solvents used in the oxidation reaction include nochloromethane, ethyl ether, tetrahydrofuran, and benzene. There are no particular restrictions on the amount of these organic solvents to be used, and they can be selected as appropriate; for example, about 5 to about 2 ol) can be used for the compound of formula (7).

To synthesize the above compound (5) from the compound of formula (6) that can be synthesized as described above, the compound of formula (6) is mixed with hepterident triphenylphosphorane in an organic solvent.
(C5H5)sP=cH(CH) can be easily synthesized by Wittetz reaction with 5CHs.

This Uitztetsug reaction is usually, for example, about -10@ to about 0
The treatment can be carried out at a temperature of about 0.degree. C. for about 1 to about 6 hours. The amount of hepterident triphenylphosphorane used in the reaction is preferably in the range of about 1 to about 2 moles per 1 mole of the compound of formula (6). Preferred examples of organic solvents often used in this reaction include ethyl ether, tetrahydrofuran, benzene, N,N-)methylformamide, and acetonitrile. There are no particular restrictions on the amount of these organic solvents to be used, and they may be selected as appropriate. For example, the amount used may preferably be in the range of about 5 to about 20% by weight based on the compound of formula (6).

After the reaction is completed, the compound of formula (5) can be easily obtained with high purity and good yield by post-treatment according to a conventional method.

The above compound of formula (4) can be easily synthesized from the compound of formula (5) which can be synthesized as described above by carrying out a catalytic reduction reaction in an organic solvent in the presence of a reduction catalyst.

As the reduction QpJ used in this reaction, for example,
Preferred examples include Soumu Carbon, Nozo Radium Black, and Raney Nickel. The preferable amount of these reducing agents used is, for example, about 5 to about 20% by weight based on the compound of formula (5). Preferable examples of the organic solvent include methanol, ethanol, ethyl ether, and acetic acid. There are no particular restrictions on the amount of these organic solvents to be used, and they may be selected as appropriate.
5) The amount used can preferably range from about α5 to about 5 times the weight of the compound.

The conditions for the reduction reaction can be selected and changed as appropriate; for example, the reduction reaction can be carried out under conditions of hydrogen pressure at normal pressure and temperature in the range of about 10<6>C to about 30<0>C.

After completion of the reaction, the compound of formula (4) can be obtained with high purity and good yield by post-treatment according to a conventional method.

In order to synthesize the above formula (3) compound from the formula (4) compound that can be synthesized as described above, it can be easily synthesized by lactonizing the formula (4) compound in the presence of an acid catalyst. Can be done.

The lactonization reaction, for example, preferably ranges from about 0.6 to about 20
This can be carried out by reacting for about 2 to about 6 hours under temperature conditions in the range of about .degree.

Preferred specific examples of the acid catalyst used in the lactonization reaction include 1N-hydrochloric acid, 70% acetic acid, 90% trichloroacetic acid, and the like. The amount of these acid catalysts to be used is, for example, about 5 to
A preferable range is about 20% by weight.

After completion of the reaction, the compound of formula (2) can be obtained with high purity and good yield by post-treatment according to a conventional method.

The compound of formula (2) can be easily synthesized by reacting the compound of formula (3) with methyl orthoformate. The reaction can be easily carried out, for example, at a temperature in the Σ range of about 20 DEG to about 80 DEG C., and for a reaction time in the range of about 0.5 to about 1 hour. The amount of methyl or)-f acid used in this reaction is preferably in the range of about 1.54 to about 5 mol per 1 mol of the compound of formula (3).

After completion of the reaction, the compound of formula (2) can be easily synthesized with high purity and good yield by post-treatment according to a conventional method.To synthesize -4-olide, for example, it can be obtained as described above. It can be easily synthesized by thermally decomposing a compound of formula (2) in the presence of an acid catalyst. Examples of the reaction temperature and reaction time for this thermal decomposition include temperature conditions in the range of about 120° C. to about 150° C. and reaction time in the range of about 2 to about 4 hours. A preferred specific example of the acid catalyst used for thermal decomposition is, for example, acetic anhydride. The amount of acid catalyst used is:
A preferable range is, for example, about 5 to about 20% by weight based on the compound of formula (2).

After the reaction is completed, the compound of formula (1) can be easily obtained with high purity and good yield by post-treatment according to a conventional method.

Thus, 2f+) (R, Z) obtained by the method of the present invention
The degree of light absorption of -5-tetradecene-4-olide is (α]”,
7-70.4° (CHCL3), and the bean beetle (
The optical intensity [α] of the male attractant (R,z)-5-tetradecen-4-olide isolated from Japan (Japanese) -70,1@(CHCLs), and other quictor data also completely matched with the standard material.

The embodiments of the method of the present invention will be explained in more detail below by giving examples.

(Example) fll (22,4R,5S,6R)-4-0-pe7
Synthesis of Sol-4,5,6,7-tetrahydroxy-5,6-isopropylidene-2-ethyl hepetenoate formula (7).

(-) -2-0-pentrue 5.4-0-isopropylidene-D-arabinopyranose formula (8) 1o, 6g (
0,05s5S) and carboethoxymetherenetrifenylphosphorane 199 (0,057 mol) are dissolved in sochloromethane 50- and stirred at 10° to 20° C. for 6 hours.

The solution is concentrated under reduced pressure, the residue is suspended in petroleum ether/ether ether, and the insoluble materials are separated. The oral fluid was passed through Silica Glu 50I, and the fractions containing the target compound were collected and concentrated.12.11 (Yield 95%)
I got it. (α)”p −22,4@(c==1.p,
MCott').

+21 (2Z, 4/?, 5S, 6S)-4-0-benzo-7-oxy-4,5,6-drihydroxy 5
．． Synthesis of ethyl 6-0-isopropylidene-2-heptene salt formula (6).

Dissolve 5 g (14.5 mmol) of the compound of formula (7) in 20 rnl of nochloromethane,
Add # (23 mmol) in small portions. Stir vigorously at room temperature (6 hours) and add 1 1 oz of ethyl ether.
Add 00ze. Stirring was continued for an additional 30 minutes, and the supernatant liquid was collected and passed through a 50 g silica del column. aldehyde)'
Reacts with the reagent (2,4-nonitrophenyl hydracion). Collect and concentrate fractions.

The target compound was obtained as a syrup, which was immediately diluted with 50 ml of tetrahydrofuran to avoid unstable compounds and used in the next reaction.

+31 (4R,5R,6R>-a-o-pentrue-4.5.6-)lihydroxy-5.6-0-isopropylidene-2,7-titradecanoenoic acid ethyl synthesis of formula (5).

3.8 g (a 64 mmol) of ruheptane triphenylphosphonium puromito are suspended in 100 ml of tetrahydrone and cooled to -5°C. Continue stirring for 30 minutes at -5°C. While continuing to stir vigorously, 2 g (5.99 mmol) of the compound of formula (6) was dissolved in tetrahydrofuran!
20 rnl was added dropwise, and after the addition was completed, stirring was carried out at -5°C for 5 hours. The mixture is poured into an ice-cooled saturated saline solution (50°C), and the mixture is extracted with ethyl ether or ethyl acetate. The extract was dried over anhydrous sodium sulfate, concentrated, and further purified with silica powder using petroleum ether/ether ether (20,9
). The effluent was collected and concentrated to yield 2.1 g of Eq.
The compound was obtained as a mixture of double bond geometric isomers. The ratio of the 2E- and 2-Z isomers in this mixture is III-NM
The ratio was determined to be 7:2 from the R spectrum chart.

'NMR of 2E: 6.85ppm (dd, 6.1Hz, 15.9Hz
-CH=CHC00 C1H! ), 6.07ppm (dd, 1.2H1,15,9II
z -CH=CHC00C! "II), 'H-NMR of 2Z integral; 6.30 ppm (ddd, 2.7 Hz% a6EZ, 1
1.7Z, -CH= CH-C00C, II,) 5.94ppm (dd, 1.0Hz, 11.7H
z -CH=CHC00 CxHs) Elemental analysis value of mixture; Measured value (', 72.19% H, a81% calculated value C
,72,07% 118.75%IR(ycx-1):
2950, 2850.1720.1080 The above isomers can be used in the next reaction without separation.

Synthesis of +41<5R,55,6R)-4,5,6-dolyhydroxy-5,6-0-inglobylidene-ethyl tetradecanoate formula (4).

1.9 (2.4 mlJ mol) of isomer mixture compound formula (5) was dissolved in 5% acetic acid-methanol solution 20-20%, and hydrogen reduction was performed at room temperature and pressure with Pd-Black 100~6.
After a period of time, the catalyst is removed and the oral liquid is concentrated under reduced pressure.

The syrup obtained as a residue was determined by thin layer chromatography and JR spectrum to contain 40-60% ethyl ester compound (4) and 40-60% lactone C (
4R,S,S,6R)-4,5,6-)rihydroxy-5.6-〇-isopropylidene-tetradecanoic acid-4-
It was confirmed that the mixture was a mixture of This amphoteric acid gives the same product in the next reaction, so it can be used as it is without separation.

+51 <4R,5R,6R)-4,5,6-trihydroxytetradecane@-4-olide Formula (3) Formula (4
) A mixture of compound and lactone 700μ is 10-90
% aqueous trifluoroacetic acid and continue stirring at room temperature for 5 hours. Benzene/toluene (!l/1) mixture 20
- was added, and the mixture was concentrated under reduced pressure to obtain 558 cm of crystals of the compound of formula (3) (yield: 90% from formula (5)).

m, p 96-97.5℃, [α]〒-1aO11(
C = 1.0, M g OH) Elemental analysis value; Measured value C, 64,82% H, 10,34% Calculated value
C, 65,07% Hllo, 15% (6) (4R
,5S,6R)-4,5,6-drihydroxy5.6
-O-(1-methoxyethylidene)-tetradecane-4
- Synthesis of oride formula (2).

Compound 300# (1.16 mmol) of formula (3) was dissolved in sochloromethane 20-7)-) luenesulfonic acid 5
Stirring of the cape and 500 μm (2.8 mmol) of methyl orthoformate is continued at room temperature for 50 minutes. The solution was passed through a silica gel column (10F) to concentrate the oral fluid. The obtained formula (2
) Since the compound is unstable, it was used immediately in the next reaction.

(7) Synthesis of (R,Z)-5-tetradecen-4-olide formula (1).

600 μm (1 mmol) of the compound of formula (2) was added to 15 μm of acetic anhydride.
- and heated to 140°C in an oil bath. After 1.5 hours, the reaction solution was cooled to 10°C, 20 ffI/saturated aqueous sodium carbonate solution was added, and the mixture was stirred at 10°C for 4 hours. Extract the mixture with chloroform (10-x5). Wash the extract with saturated hydrogen carbonate solution, then water,
Dry with magnesium sulfate. The syrup obtained after concentration is distilled under reduced pressure to a boiling point of 100° to 105°C/CJ.
, 210 ■ fraction with mH9 at 55°C (yield 90%)
I got it.

[α)”I;-70,4@(C=Q,4,CHCZ,)
Elemental analysis values: Measured value C174, 88% Hllo, 68% calculated value
C, 74,94% H, 10,80%'H-NMRδ(
ppm): 190 (5H, broadt), 1. sO~
1.40 (14H, m), 1.93 (1H, m), 2.
10 (2H% m), 2.35 (H, m), 2.51
(11%m), 5.19 (1H, did), 5.
44 (11% F+ri, 5.63 (IH, d-dd)
.

(Effects of the Invention) According to the present invention,
(RlZ)-5 useful as a sex pheromone for
It is possible to provide a method by which -tetradecen-4-olide can be easily produced industrially at low cost and with high purity.

That is, especially in the synthesis of the compound of formula (8) using D-arabinose or D-glucose as an asymmetric source,
As ztap, this is a novel method that does not involve racemization during the reaction process and can easily deal with the problem of epimerization by creating a plurality of asymmetric carbon atoms. A compound of formula (1) having a side chain double bond can be produced with high purity.

Procedural Amendment October 3, 1988 Director of the Japan Patent Office Kuro 10 Akio 1, Indication of the Case 1985 Patent M No. 203822 2, Title of Invention (R,Z)-5-tetradecene-4-olide Manufacturing method 3,
Relationship with the case of the person making the amendment Patent Applicant's Name: Asutanigawa Perfume Co., Ltd. 4, Agent: 107 (1 idiot) Telephone: 2 585-225 G 5, Self-initiated request for amendment) 6, Amendment Contents of the “Claims” column and “Detailed Description of the Invention” in the counter specification and the content of the amendments are as shown in the attached sheet (Attachment) [Description in the “Scope of Claims” column of 1 Specification H of,
The following corrections are made.

rt, "t" (4R, 5S, 6R)-4,5,6-)lihydroxy-5,6-O-(1-methoq-sietyridine) represented by the formula (2)
-Tetradecane-4-olide is thermally decomposed into r in the presence of an acid catalyst.
-Production method of Olide.

2. The compound of formula (2) is represented by the following formula (83) provided that in the formula, ■
(represents a benzyl group, represented by (-)-2-0~benzoyloxy-3゜4-0-impropylidene-a, D-arabi/-), carboalkoxytriphenylphosphorane 1 (ca[ 1,
), I) = C11・COOR', where R' represents a methyl group or an ethyl group.
tig) to react with the following formula (7), where R and r (' are the same as above, 11' f
i b % t'L le(2l @ 4 R* 5 S
g 6 R) -4-0-pentrue-4,5.6-tetrahydroxy-5,6-0-inpropylidene-2-
Form an alkyl heptenoate, and then oxidize the compound of formula (7) in the presence of an oxidizing agent to obtain the following formula (6), where I and R' have the same meanings as above (2 !, ,4 Rv5 S-68E4-0-benzoyl-'?-okine-4.5.6-)rihydroxy5
6-0-Impropylidene-2-alkyl heptenate is formed, and then the compound of formula (6) is converted to hepnalidenetriphenylphosphorane lc. H, P=CH(CII
2) 5CH:1. I and Wittig make F
Description (5) However, in the formula, ■ (and R' is -1-written j, also known as question circle-pk wasa iru (4 R.5 S.6 R) -4-
0-penflu 4,5,6-trihydroxy-5,6
-0-Isopropylidene-2,7-tetradecanoenoic acid alkyl is formed, and then the compound of formula (5) is subjected to a catalytic reduction reaction in the presence of a reducing agent to form the compound represented by the following formula (4) (4 R ,5 raw.6 R)-4.5 ,6-
) ') to form an alkyl hydroxy-5+6-0-impropylidene-tetradihydroate, then formula a (
4) Lactonized in the presence of a compound and an acid catalyst and represented by the following formula ('SR.5S*6R)-4-5,b-)
7/l'111 characterized in that it is formed by forming lyhydroxytetradecanoic acid-4-olide and then reacting a compound of formula a (:() with methyl orthoformate.
'# The scope of the search: The manufacturing method of the first battle. 1111 The statement in the "Detailed Description of the Invention" column of the specification is corrected as follows.

(1) Specification NF rjrJu page 2 line [1 arrow] -hni l'L iA 11jl is corrected to rL iA Ill -J.

(2) Clear mvlFtjS13rc 2nd line /r. Under the arrow at the end, the text 1-pyridinium chlorochromate 1 has been corrected to ``pyrinonimum chlorochromate.''

(3) Formula (5) at the right end of page 13, line 2 of specification ffi [1] should be corrected as follows.

[(1) Specification 11F, page 13, line 3 [In the leftmost arrow of J, 11'del is corrected to jl)tl-CJ +1 mir.

(5) On page 23, lines 4-5 of the specification, the text "I bilinonium chlorochromate" is corrected to "bilinonium chlorochromate."

(6) In the 5th line from the bottom of No. 23 of the specification, “(4R, SR,
6R) J should be corrected as ``(4R, 5S, 6 R) J.

7) I-CI (= CI-I
Correct C00J to [-CI=(j(COOJ).

(8) In the 3rd line from the bottom of specification 125, 1-(SR,5S
, 6R)J is corrected to r(4R,5Sj6 R)J.

(9) In line 2609 of the specification, l'(4R, S, Sj is corrected to [(4R, 5SJ).

(10) In the 5th line from the bottom of No. 26 of the specification, [(4R, 5[
< , G R), 1 is corrected to r(4[t, 5 S, G R) J.

Claims (1)

[Claims] 1. (4R,5S,6R)-4,5,6-trihydroxy-5,6- represented by the following formula (2) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (2) O-(1-methoxyethylidene)
-Tetradecane-4-olide is thermally decomposed in the presence of an acid catalyst.The following formula (1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(1) (R,Z)-5 -Production method of tetradecene-4-olide. 2. The compound of formula (2) has the following formula (8) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (8) However, in the formula, R represents a benzyl group, (-)-2-O- benzoyloxy-3,
4-O-isopropylidene-α,D-arabinose was converted into carbalkoxytriphenylphosphorane [(C_6H_
5)_3P=CH-COOR', where R' represents a methyl group or an ethyl group] and Wittig
) to react with the following formula (7) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (7) However, in the formula, R and R' have the same meaning as above, and it is expressed as (2Z, 4R, 5S, 6R) -4 -O-benzyl-4,5,6-tetrahydroxy-5,6-O-
Alkyl isopropylidene-2-heptenoate is formed, and then the compound of formula (7) is subjected to an oxidation reaction in the presence of an oxidizing agent to form the following formula (6) ▲ Numerical formula, chemical formula, table, etc. ▼ (6) However, In the formula, R and R' have the same meaning as above, and (2Z,4R,5S,6S)-4-O-benzoyl-7-oxo-4,5,6-trihydroxy-
to form alkyl 5,6-O-isopropylidene-2-heptenoate, and then convert the compound of formula (6) into heptylidenetriphenylphosphorane [C_6H_5P=CH(C
H_2)_5CH_3] is reacted with the following formula (5) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (5) However, in the formula, R and R' have the same meaning as above, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼(5) However, in the formula, R has the same meaning as above, R' represents a CH_3 group or a C_2H_5 group, and (4R,5S,6R)-4-O-benzyl-4,5,6-tri -Hydroxy-5,6-O-isopropylidene-2,7-tetradecadienoic acid alkyl is formed, and then the compound of formula (5) is subjected to a catalytic reduction reaction in the presence of a reducing agent to form the following formula (4) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (4) Form an alkyl (4R,5R,6R)-4,5,6-trihydroxy-5,6-O-isopropylidene-tetradecanoate represented by The compound of formula (4) is lactonized in the presence of an acid catalyst to form (4R,5S,6R)-4,5,6, which is represented by the following formula (3) ▲Mathematical formulas, chemical formulas, tables, etc.▼(3) -trihydroxytetradecanoic acid-4-olide is formed;
2. The method according to claim 1, wherein the compound of formula (3) is then reacted with methyl orthoformate.