JPH0520417B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel octadecene derivative and a method for producing the same.

The octadecene derivative of the present invention is a novel compound that has not been described in any literature, and includes the 7S, 8R-form and its mirror image (enantiomer) represented by the following general formula [].
It includes both 7R and 8S forms.

[In the formula, R ₁ represents a hydrogen atom or a lower alkylcarbonyl group, and R ₂ represents a hydrogen atom, a lower alkylcarbonyl group, or an ethoxyethyl group. ] Examples of the lower alkylcarbonyl group represented by R ₁ and R ₂ in the above general formula [] include alkanoyl groups having 1 to 4 carbon atoms, such as acetyl, propionyl, butyryl, and isobutyryl groups.

The octadecene derivatives represented by the above general formula [] and enantiomers thereof of the present invention are (5S, 6R)-(+)- and (5R, 6R)-(+)- and (5R,
It is useful as an intermediate for the synthesis of 6S)-(-)-6-acetoxy-5-hexadecanolide, and itself is useful as a fragrance or a raw material for its production.
In particular, when the octadecene derivatives of the present invention (7S-8R-form and 7R,8S-form) are used to produce the mosquito oviposition-inducing pheromone, no by-products such as diastereomers are observed, and the separation thereof The desired enantiomer can be obtained stereoselectively without the need for other substances, and its optical purity is also very excellent (usually about 98
% or more), and compared to known methods, it has the advantage that the target product can be obtained easily with a shorter number of steps and at a considerably high total yield (up to about 10% or more).

In the following derivatives of the present invention, represented by the general formula []
Taking the 7S, 8R body as an example, its production and the 7S, 8R body
The production of the above-mentioned (5S,6R)-(+)-6-acetoxy-5-hexadecanolide from the -isomer will be described in more detail by giving a reaction scheme.

[In each formula, R ₁ and R ₂ are the same as above. R ₂ ′ represents a hydrogen atom or an ethoxyethyl group, and R ₂ ″ represents a hydrogen atom or a lower alkylcarbonyl group.] That is, the present invention in which R ₁ is a hydrogen atom and R ₂ is an ethoxyethyl group in the general formula [] The 7S, 8R- form of (±)-1-tridecene-3- is represented by the formula []
Using ol as a starting material, it is reacted with D-(-)-diisopropyl tartrate to obtain a compound of the general formula [] in which R ₂ ' is a hydrogen atom, and then this compound is reacted with ethyl vinyl ether to obtain R ₂ ' group is protected with an ethoxyethyl group, and the thus obtained 1,
It is obtained by subjecting 2-epoxy-3-tridecanol ethoxyethyl ether to a Grignard reaction with 4-methyl-3-pentenylmagnesium halide.

The compound of formula [] used as a starting material in the above is known and can be easily obtained, for example, by reacting undecanal with a Grignard reagent such as ethylene magnesium bromide.

The reaction between the compound [] and diisopropyl tartrate was described by K.B.Sharpless et al.
method [J.Am.Chem.Soc., 103 , 6237 (1981)]
It can be done according to. As a preferable example of the reaction, for example, each raw material compound is placed in a suitable container, and 0.0 A method of stirring at a temperature below .degree. C., preferably around -20.degree. C. can be mentioned. The proportions of raw materials and other reagents to be used are determined as appropriate;
Although not particularly limited, preferably at least an equivalent amount of diisopropyl tartrate to the compound [],
Usually 1 to 1.5 times equivalent, about 2 times hydroperoxide
It is preferable to use approximately twice as much titanate, and approximately equivalent amount of titanate.

In this way, a compound (1,2-epoxy-3-tridecanol) of the general formula [] (R ₂ '=H) is obtained. In particular, in the above reaction, depending on the stereospecificity of diisopropyl tartrate used as a raw material, if the D-(-)-form is used, the 2S,3R-form is used, and if the L-(+)-form is used, the 2R,3S- can be synthesized selectively and in high yield. The optical purity of the obtained target is determined by the corresponding α
- Methoxy-α-trifluoromethylphenylacetate measured by HPLC analysis (column: Partecil 5, 25 x 4.6 mm, solvent: n-hexane: dichloroethane = 2:1, 30 Kg/cm ² , detection: 217 nm), Usually about 90% or more.

The reaction of the compound of the general formula [] (R ₂ ′=H) obtained above with ethyl vinyl ether is preferably carried out by adding the compound of the general formula [] (R ₂ ′=H) to a dry ethyl ether solution. This is done by adding about 4 to 10 times the equivalent of ethyl vinyl ether and about ₂ mol % of p-toluenesulfonic acid, and stirring at about 0 to 5°C for several hours. A compound of the general formula [ ] (R ₂ ′=EE) in which is protected by an ethoxyethyl group (EE) group can be obtained.

The compound of the general formula [] (R ₁ = H, R ₂ = EE) of the present invention has the general formula [] obtained as above.
It is produced by reacting the compound (R ₂ '=EE) with 4-methyl-3-pentenylmagnesium halide, preferably bromide, to extend the carbon chain. The carbon chain extension reaction is described, for example, in the literature by G. Linstrumelle et al [Tetrahedron Letters].
Lett., 1503 (1979)]. The process is preferably carried out in the presence of copper bromide (Cu ₂ Br ₂ ) in a suitable solvent, such as tetrahydrofuran, for about 1 to 2 hours at a temperature of about -30°C to about room temperature. It is done. The amount of 4-methyl-3-pentenylmagnesium halide to be used for the compound of the general formula [] (R ₂ ′=EE) is usually preferably about 3.0 times equivalent, and the amount of copper bromide used is usually about 0.3 times equivalent. It is better to do so.
The above carbon chain extension reaction has no effect on the stereospecificity of the starting compound []. Therefore, when the 2S, 3R- form is used as the compound [], the target compound [] is the 7S, 8R- Body is,
When the 2R,3S-form is used, the 7R,8S-form is selectively obtained.

The compound of the present invention in which R ₁ and R ₂ are both hydrogen atoms in the general formula [] and its enantiomer has the general formula [] (R ₁ = H, R ₂ = EE) obtained by the above.
Produced by removing the EE group at position 8 from the compound (7S, 8R-form) or each of its enantiomers (7R, 8S-form) using an appropriate acid such as hydrochloric acid according to a conventional method. can. The elimination reaction is usually carried out in a solvent such as tetrahydrofuran at about 0° C. for about 1 hour.

The compounds of the present invention in which at least one of KR ₁ and R ₂ is a lower alkylcarbonyl group and enantiomers thereof have a diol obtained by the elimination reaction of the EE group described above, and a lower alkylcarboxylic acid or a functional group derivative thereof, such as an acid It is obtained by subjecting anhydride or acid halide to an esterification reaction. This esterification reaction is carried out according to a conventional method. Preferably, the reaction is carried out by using an acid anhydride such as acetic anhydride and stirring in a solvent such as pyridine at a temperature of 0° C. to room temperature for about 2 to 12 hours. In the above, the amount of the lower alkyl carboxylic acid or its functional group derivative to be used can be determined arbitrarily, and the compound of the present invention in which both or either of R ₁ and R ₂ are esterified can be obtained accordingly. In addition, the compound of the present invention in which R ₁ is a lower alkylcarbonyl group and R ₂ is a hydrogen atom is obtained by first performing the above esterification reaction on a compound of the general formula [] (R ₁ = H, R ₂ = EE) or an enantiomer thereof. , R ₁ is a lower alkylcarbonyl group and R ₂ is EE
It can also be obtained by obtaining a compound of the general formula [] or its enantiomer, which is a group, and then subjecting it to a de-EE reaction.

The compound of the present invention obtained as described above can be isolated and purified by conventional separation means. Examples of the separation means include extraction methods, distillation methods, recrystallization methods, column chromatography, and combinations thereof.

Examples of the synthesis of mosquito egg-laying attracting pheromone from the compound of the present invention will be described in detail below.

First, the compound of the present invention [] (R ₁ =R ₂ =lower alkylcarbonyl) is oxidized to cleave its double bond. This oxidation reaction can be carried out according to a general method, but is preferably carried out according to the method described by Shearpress et al. (KBSharpless et al.
Catalytic RuO ₄ oxidation [J.Org.Chem., 46,
3936 (1981)]. The contact RuO ₄
Oxidation is carried out in the presence of an oxidizing agent such as sodium periodate, in carbon tetrachloride, acetonitrile and water solvent,
It is carried out using a ruthenium chloride (RuCl ₃ ) catalyst at room temperature with stirring. Through this reaction, the general formula [] (R ₁
=R ₂ ″=lower alkylcarbonyl group) is obtained.

Next, the above carboxylic acid is hydrolyzed to give a dihydroxy acid of the general formula [] (R ₁ =R ₂ ″=OH).
This reaction is carried out under conventional hydrolysis reaction conditions. It is preferably carried out using a basic compound such as potassium carbonate in a suitable solvent such as methanol.

The resulting dihydroxy acid is then thermally cyclized (lactonized) to form the general formula []
(R ₂ ′=OH) hydroxylactone is obtained, and by acetylating it, the desired 6-
Acetoxy-5-hexadecanolide []
(R ₂ ′=acetyl group) can be obtained. The above lactonization and acetylation are both carried out according to conventional methods. Preferably said lactonization is about
By heating at 150-170℃ for about 10-30 minutes,
In addition, acetylation is performed using an excess amount of acetic anhydride.
This is carried out in pyridine by stirring overnight at about 0° C. to room temperature.

In each of the above reaction steps, the steric properties of the starting compound are not impaired, and therefore, from the compound of the present invention of the general formula [], that is, the 7S,8R-form, the compound of the general formula []
After passing through 5S and 6R- bodies, the object of the general formula [], i.e.
The 5S and 6R-isomers can be obtained with extremely high optical purity and in high yield. Furthermore, from the enantiomer, ie, 7R,8S- form of the compound of the present invention of the general formula [],
Similarly, the desired 5R,6S-isomer can be produced in substantially the same manner with extremely high optical purity and yield.

The obtained 6-acetoxy-5-hexadecanolide is isolated and purified from the reaction system by chromatography, recrystallization, etc. according to conventional methods, and (5S, 6R)
Both the -(+)- body and the (5R,6S)-(-)- body are active as mosquito oviposition-inducing pheromone, and in particular, the (-)- body has approximately the same activity as the (+) body. 6 times higher, making it useful as an attractant, for example in the pest control field.

In order to explain the present invention in more detail, examples of the production of the compound of the present invention will be given below as examples, and then an example of the production of 6-acetoxy-5-hexidecanolide from the compound will be given as a reference example. In each case, the infrared absorption spectrum (IR) was measured using a Jasco A-102 spectrometer using a film in the case of an oily substance and a nudiol in the case of a crystalline substance. Nuclear magnetic resonance spectra (NMR) were performed at 60MHz, unless otherwise noted.
Measurement was performed using a Hitachi R-24A spectrometer using TMS as an internal standard reagent. Optical rotation was measured with a Jasco DIP-140 polarimeter.
HPLC analysis was performed using a Shimadzu LC-2 chromatograph.

Example 1 Synthesis of 1,2-epoxy-3-tridecanol (a) (2S,3R)-isomer Ti(i-PrO ₄ ) ₄ 14.9 ml and diisopropyl D-
(−)-Tartrate ester 12.5ml was cooled and dried.
under argon atmosphere and stirring in 500 ml of CH ₂ Cl ₂ .
Added while cooling to −23° C. (dry ice and CCl ₄ ). The mixture was stirred for 5 minutes, followed by (±)−
9.92 g of 1-tridecen-3-ol and
t- dissolved in 7.32M (13.7ml) _{of CH2Cl2}
BuOOH was added to the stirred cooled mixture. After addition,
Store the reaction mixture in a deep freezer at −20°C.
I left it for 17 hours. The flask was then cooled to -23°C again with stirring. To the stirred and cooled mixture was added 225 ml of 10% L-(+)-tartaric acid in _H20 . Stirring was continued for 30 minutes at -23°C and then for 1.5 hours at room temperature. Separate the organic solution, wash with water and dilute with Na ₂ SO ₄
and concentrated under vacuum. Ether the residue
It was diluted with 375 ml and cooled to 0-5°C with stirring.
This was mixed with 150ml of 1N NaOH and the mixture was
Stir for 30 minutes at ~5°C. The ethereal solution was washed with aqueous NaCl, dried over Na ₂ SO ₄ and concentrated under vacuum. The residue was purified by chromatography ( _SiO2 ) and distilled to give 2.99 g (55.7% yield) of (2S,3R)-1,2-epoxy-3-tridecanol.

bp112～113℃／0.35mmHg mp25～26℃ [α] ²⁰ _D = −16.6° (c=1.12, CHCl ₃ ) ν _nax = 3400(s), 1065(m), 850(m), 835(m) cm ^-1 δ (CDCl ₃ ) = 0.89 (3H, deformed t, J = 7
Hz) 1.0 ~ 1.7 (18H, br.) 2.02 (1H, br.) 2.60 ~ 3.08 (3H, m) 3.80 (1H, m) Actual value: C = 72.78; H = 12.22% As C ₁₃ H ₂₆ O ₂ Calculated value: C=72.84; H=12.23% (2S,3R)-1,2-epoxy-3 obtained above
-tridecanol ([α] ²⁰ _D = -16.1° (C = 2.48,
CHCl ₃ )) The optical purity of the sample is determined by the corresponding (S)−α−
HPLC analysis of methoxy-α-trifluoromethylphenylacetate (MTPA ester) (column: Partesil 5, 24 x 4.6 mm, solvent: n- _hexane : _ClCH2CH2Cl =2:1 mixture, 30Kg/cm2 ^,
217nm detection).

As a result, the optical purity of the sample was 92.1%.

(b) (2R,3S)-isomer Using diisopropyl L-(+)-tartaric acid, (3R,3S)-1,2-epoxy-3-
2.70 g (yield 50.2%) of tridecanol was obtained.

bp=109~110℃/0.25mmHg mp25~26℃ [α] ²⁰ _D = +16.2゜ (c=1.01, CHCl ₃ ) Actual value: C = 72.79; H = 12.20% as C ₁₃ H ₂₆ O ₂ Calculated value: C = 72.84; H = 12.23% Above (2R, 3S)-1,2-epoxy-3-tridecanol ([α] ²⁰ _D = +15.7° (C = 2.09, CHCl ₃ )
)
The optical purity of was measured under the same conditions as in (a) above. As a result, the optical purity was 86.6%.

Synthesis of 1,2-epoxy-3-tridecanol ethoxyethyl (EE) ether (a) (2S,3R)-isomer 13 ml of ethyl vinyl ether and 30 mg of p-toluenesulfonic acid were stirred and cooled (2S,3R)-isomer. 3R)-1,2-epoxy-3-tridecanol in 4 ml of dry ether. Stirring was continued for 4 hours at 0-5°C and then for 1 hour at room temperature. The mixture was washed with NaHCO ₃ solution and NaCl aqueous solution, dried over MgSO ₄ and concentrated under vacuum. The residue was purified by chromatography (SiO ₂ ),
Distilled to give 3.68 g of (2S,3R)-1,2-epoxy-3-tridecanol EE ether (yield 85.1%)
I got it.

bp107~112℃/0.35mmHg n ^21.5 _D = 1.4359 ν _nax = 1130 (m), 1090 (m), 1060 (m) cm ^-1 δ (CCl ₄ ) = 2.5 ~ 2.8 (3H, m) 3.0 ~ 3.7 ( 3H, m) 4.62 (1H, m) Actual value: C = 71.58; H = 12.06% Calculated value As C ₁₇ H ₃₄ O ₃ C = 71.28; H = 11.96% (b) (2R, 3S)-isomer Above −Similarly to (a), (3R, 3S) −1,2−
3.33 g (yield: 85.3%) of (2R,3S)-1,2-epoxy-3-tridecanol EE ether was obtained from 2.70 g of epoxy-3-tridecanol.

bp107~112゜/0.35mmHg n ^21.5 _D = 1.4359 Actual value: C = 71.29; H = 12.14 Calculated value (as C ₁₇ H ₃₄ O ₃ ): C = 71.28; H = 11.96% 2-Methyl-2-octadecene- Synthesis of 7.8-diol 8-ethoxyethyl (EE) ether (a) (7S,8R)-isomer Me ₂ C=CH(CH ₂ ) ₂ MgBr in dry THF (1.23 M,
33 ml) solution was dried with 550 g of Cu ₂ Br ₂ stirred and cooled (dry ice and diethyl ketone).
In 8 ml THF suspension at -30℃ under argon atmosphere.
It was dripped. Stirring was continued for 10 minutes. (2S, 3R) −
A solution of 3.68 g of 1,2-epoxy-3-tridecanol EE ether in dry THF (5 ml) was added dropwise to the stirred and cooled mixture at -30<0>C.
Stirring was continued overnight and the temperature was gradually returned to 0°C. The mixture was poured into 150 ml of saturated NH ₄ Cl solution and extracted with 600 ml of n-hexane. The extract was dried with MgSO ₄ and concentrated under vacuum. The residue was purified by chromatography ( _SiO2 ) to give (7S,8R)-2-methyl-2-octadecene-7,8-diol 8-
4.47 g (yield 94.5%) of EE ether was obtained.

(b) (7R,8S)-isomer 3.33 g of (3R,3S)-1,2-epoxy-3-tridecanol EE ether in the same manner as above.
4.16 g of (7R,8S)-2-methyl-2-octadecene-7,8-diol EE ether
(yield 96.4%).

Example 2 Synthesis of 2-methyl-2-octadecene-7,8-diol (a) (7S,8R)-isomer (7S,8R)-2-methyl-2-octadecene-
7,8-diol EE ether 4.47g THF20
ml and 4 ml of 0.5NHCl solution were stirred at 0° C. for 1 hour and then at room temperature for 1 hour. The solution is then saturated
Neutralized with _NaHCO3 solution and extracted with ether. The ether solution was dried with _MgSO4 , concentrated in vacuo, and
3.40 g of (7S,8R)-2-methyl-2-octadecene-7,8-diol in crystalline form (yield 94.4
%) was obtained. Analytical samples were recrystallized from n-hexane.

mp87～88℃ [α] ^20.8 _D −1.07゜(c=0.80, CHCl ₃ ) ν _nax =3320(s), 3230(s), 1070(s), cm ^-1 δ(100MHz, CDCl ₃ ) 0.84( 3H，deformedt，
J = 7Hz), 1.0 to 1.5 (-22H), 1.56 (3H,
s), 1.60 (3H, s), 1.7-2.3 (2H), 1.96
(2H, s), 3.40 (2H, m), 4.85 (1H, m) MS: m/z298.2890 (as calculated value C ₁₉ H ₂₃ O ₂
298.2872) (b) (7R,8S)-isomer In the same manner as above, (7R,8S)-2-methyl-
2-Octadecene-7,8-diol 3.28 g (7R,8S)-2-methyl-2-octadecene-7,8-diol from 4.16 g EE ether (yield
97.9%).

mp87-88℃ [α] ^21.5 _D = +1.08゜ (c = 1.02, CHCl ₃ ) MS: m/z = 298.2838 (calculated value C ₁₉ H ₃₈ O ₂
as: 298.2871) Example 3 Synthesis of 2-methyl-2-octadecene-7,8-diol diacetate (a) (7S,8R)-isomer 8 ml of acetic anhydride was converted into (7S,8R)-2-methyl-2 −
It was added to a solution of 3.21 g of octadecene-7,8-diol in 25 ml of pyridine while stirring. After stirring for 4 hours at room temperature, 4-N,N-dimethylaminopyridine (DMAP, trace amount) was added to the mixture and stirring was continued for 30 minutes. The mixture was then diluted with 200 ml of ether,
1N−HCl solution, _CuSO4 solution, saturated _NaHCO3 solution,
Washed successively with water and aqueous NaCl, dried over MgSO ₄ and concentrated in vacuo. The residue was purified by chromatography (SiO ₂ ) and distilled to obtain 2.28 g (yield 55.5%) of (7S, 8R)-2-methyl-2-octadecene-7,8-diol diacetate.

bp142～145゜/0.08mmHg n ^21.5 _D = 1.4479 [α] ^21.5 _D = +1.26゜ (c = 1.19, CHCl ₃ ) ν _nax = 1743(s), 1368(m), 1242(s), 1225( s), 1020
(m)cm ^-1 δ (CCl ₄ ) = 0.88 (3H, deformed t, J = 7
Hz), 1.1~1.5 (~22H), 1.58 (3H, s), 1.66
(3H, s), 1.98 (3H, s), 1.85~2.20 (2H),
4.7-5.3 (3H, m) Actual value: C = 72.38; H = 11.16% Calculated value As C ₂₃ H ₄₂ O ₄ : C = 72.20; H = 11.07% (b) (7R, 8S)-isomer With the above Similarly, (7R,8S)-2-methyl-
From 3.21 g of 2-octadecene-7,8-diol (7R,8S)-2-methyl-2-octadecene-7,
2.93 g of 8-diol diacetate (yield 71
%) was obtained.

bp144-146℃/0.12mmHg n ^21.1 _D = 1.4477 [α] ^20.8 _D = -1.28゜ (c = 1.09, CHCl ₃ ) Actual value: C = 72.34; H = 11.10% Calculated value As C ₂₃ H ₂₄ O ₄ : C=72.20; H=11.07% Reference Example 1 Synthesis of 5,6-diacetoxyhexadecanoic acid (a) (5S,6R)-isomer (7S,8R)-2-methyl-2-octadecene-
7,8-diol diacetate 1.16g and
Into a solution of 2.63 g of NaIO ₄ in 6 ml of CCl ₄ - 6 ml of MeCN - 9 ml of H ₂ O, 16 mg of RuCl ₃ (H ₂ O) _O was added under vigorous stirring.
was added. Stirring was continued for 4.5 hours. The mixture was then diluted with 40 ml CH ₂ Cl ₂ and 15 ml H ₂ O, the organic layer was separated and the aqueous layer was extracted with CH ₂ Cl ₂ . The organic solution was collected, dried with MgSO ₄ and concentrated in vacuo. The residue was diluted with 60 ml of ether and filtered through Celite. The ether solution was dried over MgSO ₄ and concentrated in vacuo to give 1.09 g (96.6% yield) of (5S,6R)-5,6-diacetoxyhexadecanoic acid as a dark oil. This was used in the next step without further purification.

(b) (5R,6S)-isomer Same as above, (7R,8S)-2-methyl-2
-Octadecene-7,8-diol From 1.15 g of diacetate, 1.09 g (5R,6S)-5,6-diacetoxyhexadecanoic acid (yield 97.3%) was obtained.

Synthesis of 5,6-dihydroxyhexadecanoic acid (a) Add 1.0 g of (5S,6R)-isomer K ₂ CO ₃ to 15 ml of methanol solution of 1.09 g of (5S,6R)-5,6-diacetoxyhexadecanoic acid. did. The mixture was stirred at room temperature for 2 hours,
Diluted with 100ml _H2O , acidified to PH2 with 1N HCl and extracted with ether. _MgSO4 in ether solution
and concentrated in vacuo to give 950 mg (5S, 6R)-5,6-dihydroxyhexadecanoic acid solid (quantitative).
I got it. A portion of 500 mg was recrystallized twice from EtOH-petroleum ether to obtain pure (5S,6R)-5,6.
-169.4 mg of dihydroxyhexadecanoic acid was obtained.

mp135-138℃ [α] ²⁰ _D = +2.36゜ (c = 0.51, MeOH) ν _nax = 3260(s), 3160(s), 1710(s), 1695(s), 1070
(s), 1035(m), 935(m)cm ^-1 δ (C ₅ D ₅ N) = 0.86 (3H, deformed t, J = 7
Hz), 3.90 (2H, br), 8.20 (3H, br) Actual value: C = 66.83; H = 11.03% Calculated value As C ₁₆ H ₃₂ O ₄ : C = 66.63; H = 11.18% (b) (5R ,6S)-isomer Crude (5R,6S)-5,6-diacetoxyhexadecanoic acid (1.09g)
6S)-5,6-dihydroxyhexadecanoic acid 860
mg (quantitative). A portion of 500 mg was recrystallized twice to obtain 140.3 mg of (5R,6S)-5,6-dihydroxyhexadecanoic acid platelets.

mp136.5~138℃ [α] ²⁰ _D = -2.39゜ (c = 0.55, MeOH) Actual value: C = 66.65; H = 11.33% Calculated value As C ₁₆ H ₃₂ O ₄ : C = 66.63; H = 11.18 % Synthesis of erythro-6-hydroxy-5-hexadecanolide (a) (5S,6R)-isomer (5S,6R)-5,6-dihydroxyhexadecanoic acid (34.6 mg) was heated at 160°C under reduced pressure for 20 minutes. Heated. The residue was purified by TLC to give (5S,6R)-erythro-6
-Hydroxy-5-hexadecanolide 28.3mg
(yield 87.3%). 39.1 of this crude lactone
mg was recrystallized from n-hexane to obtain pure (5S,
28.3 mg of 6R)-erythro-6-hydroxy-5-hexadecanolide was obtained.

mp66.5～68℃ [α] ²⁰ _D = +12.7° (c = 0.96, CHCl ₃ ) ν _nax (KBr) = 3440(m), 2920(s), 2850(m), 1751
(s), 1265(m)1055(m)cm ^-1 δ (400MHz, CDCl ₃ ) = 0.88 (3H, t, J = 7
Hz), 1.26 (16H, br s), 1.42~1.56 (2H,
m), 1.73-1.90 (3H, m), 1.94-2.01 (1H,
m), 2.03 (1H, d, J=6Hz), 2.40-2.50
(1H, m), 2.57-2.66 (1H, m), 3.82 (1H,
m), 4.25 (1H, dt, J ₁ = 12.J ₂ = 8 Hz) Actual value: C = 71.33; H = 11.08% Calculated value As C ₁₆ H ₃₀ O ₃ : C = 71.07; H = 11.18% Above The optical purity of the obtained (5S,6R)-erythro-6-hydroxy-5-hexadecanolide was determined by NMR spectroscopy (400MHz) of the corresponding (R)-MTPA ester, and the ester was
It was confirmed that (5R,6S)-erythro-6-hydroxy-5-hexadecanolide did not contain (R)-MTPA.

δ (400MHz, CDCl ₃ ) = 0.89 (3H, t, J = 7
Hz), ~1.25 (16H, br.), 1.51~1.96 (6H,
m), 2.31 (1H, dq, J ₁ = 14, J ₂ = 8Hz),
2.54-2.63 (1H, m), 3.508 (3H, s,
OMe), 4.45 (1H, dt, J ₁ = 14.J ₂ = 5Hz),
5.32 (1H, m), 7.40 (3H, m), 7.54 (2H,
m) (b) (5R,6S)-isomer From 26.5 mg of (5R,6S)-5,6-dihydroxyhexadecanoic acid to (5R,6S)-erythro-6-hydroxy-5-hexadecanoic acid 24.9 mg (yield ~100%) of nolide was obtained.

mp67～68℃ [α] ²⁰ _D −12.5° (c=0.54, CHCl ₃ ) Actual value: C=70.86; H=11.02% Calculated value As C ₁₆ H ₃₀ O ₃ : C=71.07; H=11.18% Obtained The corresponding (R)-
It was converted into MTPA ester and subjected to NMR analysis.

δ (400MHz, CDCl ₃ ) = 0.885 (3H, t, J = 7
Hz), ~1.25 (16H, br), 1.45~1.90 (6H,
m), 2.20 (1H, dq, J ₁ = 14.J ₂ = 8Hz), 2.47
~2.56 (1H, m), 3.508 (0.03H, s, -
0Me), 3.570 (2.97H, s, -OMe), 4.35
(1H, dt, J ₁ = 14, J ₂ = 5Hz), 5.35 (1H,
dt, J ₁ = J ₂ = 5Hz), 7.39 (3H, m), 7.54
(2H, m) From the above, the optical purity of (5R,6S)-erythro-6-hydroxy-5-hexadecanolide was determined to be 98% or more.

Synthesis of erythro-6-acetoxy-5-hexadecanolide 34 mg of recrystallized lactone (5S,6R)-erythro-6-hydroxy-5-hexadecanolide was mixed with 0.1 ml of acetic anhydride and 1 ml of pyridine. did.
The solution was left at room temperature overnight to form (5S,6R)-erythro-6-acetoxy-5-hexadecanolide.
35.5 mg (yield 90%) was obtained.

[α] _D = +38.8° (c = 1.21, CHCl ₃ ) Also, 0.65 ml of acetic anhydride was added to a solution of 55.0 mg of (5S, 6R)-5,6-dihydroxyhexadecanoic acid dissolved in 3.1 ml of pyridine, and stirred. It was added at a temperature of 0 to 5°C. Stirring was continued for 3 hours. The mixture was then diluted with 20 ml of ether. ether solution with 2N-HCl,
It was washed successively with H ₂ O, CuSO ₄ solution, H ₂ O, saturated NaHCO ₃ solution and aqueous NaCl solution, dried over MgSO ₄ and concentrated in vacuo. The residue was purified by preparative TLC to give (5S,6R)-erythro-6-acetoxy-5.
-43.4 mg (yield 80.1%) of hexadecanolide was obtained.

[α] ²¹ _D = +38.4° (c = 1.41, CHCl ₃ ) ν _nax = 2930(s), 2850(m), 1745(us), 1460(w),
1370(m), 1225(s), 1190(w), 1160(w), 1050(m),
1015(w), 950(w), 925(o)cm ^-1 δ (400MHz, CDCl ₃ ) = 0.88 (3H, t, J = 7
Hz), 1.26 (16H, br.s), 1.58~1.70 (3H,
m), 1.75-1.88 (1H, m), 1.88-2.01 (2H,
m), 2.08 (3H, s), 2.40-2.50 (1H, m),
2.56-2.65 (1H, m), 3.69 (0.07H, m),
4.35 (0.93H, m), 4.86 (0.07H, m), 4.95~
5.01 (0.93H, m) This sample is erythro-6-acetoxy-5-
Threo-6-acetoxy- of hexadecanolide
It contained 7% 5-hexadecanolide.

Actual value: C = 69.02; H = 10.30% Calculated value as C ₁₈ H ₃₂ O ₄ : C = 69.19; H = 10.32% (b) (5R,6S)-isomer Recrystallized in the same manner as above (5R, 6S) −
19.2 mg of erythro-6-hydroxy-5-hexadecanolide was mixed with 0.1 ml of acetic anhydride and 1 ml of pyridine.
ml of (5R,6S)-erythro-6-acetoxy-5-hexadecanolide (yield 72
%) was obtained.

[α] _D = -38.5° (c = 0.51 (CHCl ₃ )) This was confirmed to contain no threo-isomer.

Also, from 50 mg of (6R,6S)-5,6-dihydroxyhexadecanoic acid, 49.7 mg of (5R,6S)-erythro-6-acetoxy-5-hexadecanolide (yield
83.4%).

[α] ²¹ _D = -36.2° (c = 1.39, CHCl ₃ ) This sample contained 14-15% threo-isomer according to its NMR spectrum analysis at 400 MHz.

δ (400MHz, CDCl ₃ ) = 3.69 (0.15H, m), 4.32
~4.39 (0.85H, m), 4.86 (0.14H, m), 4.95
~5.01 (0.86H, m), Actual value: C = 69.34; H = 10.17% Calculated value as C ₁₈ H ₃₂ O ₄ : C = 69.19; H = 10.32%

Claims (1)

[Claims] 1. General formula [In the formula, R ₁ represents a hydrogen atom or a lower alkylcarbonyl group, and R ₂ represents a hydrogen atom, a lower alkylcarbonyl group, or an ethoxyethyl group. ] An octadecene derivative and its enantiomer represented by: 2 formulas 1,2-ethoxy-3-tridecanol ethoxyethyl ester represented by or its enantiomer and 4-methyl-3-pentenylmagnesium halide are subjected to a Grignard reaction, and then, if necessary, deethoxyethylation and (or ) General formula characterized by carrying out an esterification reaction with a lower alkyl carboxylic acid or its functional group derivative [In the formula, R ₁ represents a hydrogen atom or a lower alkylcarbonyl group, and R ₂ represents a hydrogen atom, a lower alkylcarbonyl group, or an ethoxyethyl group. ] A method for producing an octadecene derivative or its enantiomer represented by: