JP4756185B2 - Ferroelectric liquid crystal compounds - Google Patents

Description

  The present invention relates to a ferroelectric liquid crystal compound, and more particularly to a novel ferroelectric liquid crystal compound into which an asymmetric carbon is introduced by using an enzyme reaction.

  Ferroelectric liquid crystal is one of the most actively studied liquid crystal materials and is expected as the next generation liquid crystal material. In general, a compound giving a ferroelectric liquid crystal is required to have at least a relatively flexible portion, a polar group, an asymmetric carbon, a ring structure portion, and the like. Various types are known. However, the range of materials having such a molecular structure has not necessarily been studied extensively, and only limited ones have been developed.

  On the other hand, human-friendly fine chemicals synthesis and environment-friendly reactions are being developed using enzyme reactions and the like. For example, it is also known that lipase is used as a biocatalyst having a low environmental impact, and various compounds are produced from castor oil, for example, utilizing the high substrate specificity and stereoselectivity exhibited by lipase. (Patent Documents 1 to 3, Non-Patent Documents 1 and 2). However, there has been little research on synthesizing a ferroelectric liquid crystal material using a biocatalyst having a low environmental load.

  For example, Patent Documents 4 and 5 describe a method for producing an optically active halogen atom-containing alcohol using lipase, suggesting that these may be used as raw materials for ferroelectric liquid crystal compounds. However, there is no description of the liquid crystal compounds actually obtained using these as raw materials, and accordingly, data showing liquid crystal properties has not been obtained.

Japanese Patent Laid-Open No. 02-013389 JP 2001-314735 A JP 2005-237304 A JP-A-6-056721 JP 2000-287696 A Hatanaka, Goto, “Continuous hydrolysis of castor oil with immobilized lipase”, Kitakyushu Technical High School Report, Volume 36 (January 2003), 65-70 Charlotta Turner et al, `` Lipase-CatalyzedMethanolysis of Triricinolein in Organic Solvent to Produce1,2 (2,3) -Diricinolein '', Lipids, Vol. 38 (11), 1197-1206 (2003)

  The present invention has been made in view of the above-mentioned background art, and an object thereof is to provide a novel ferroelectric liquid crystal compound.

  As a result of intensive studies to solve the above problems, the present inventor made liquid crystallinity by actually using a compound having an asymmetric carbon obtained by an enzymatic reaction as a raw material and further performing a chemical reaction. The present inventors have found a compound to be shown and completed the present invention.

  That is, the present invention provides a ferroelectric liquid crystal compound comprising an asymmetric carbon atom, wherein the asymmetric carbon atom is introduced using an enzymatic reaction. is there.

［一般式（１）中、Ｘは置換基を有していてもよい芳香族環又は連結芳香族環を示し、Ｒ^１は置換基を有していてもよい炭素数１〜２４のアルキル基又は炭素数２〜２４のアルケニル基を示し、Ｒ^２は置換基を有していてもよい炭素数１〜６のアルキル基又は−ＣＯＲ'（Ｒ'は置換基を有していてもよい炭素数１〜６のアルキル基又はフェニル基を示す）を示し、Ｒ^３は置換基を有していてもよい炭素数１〜１３のアルキル基を示す。］ Moreover, this invention provides the compound which has a chemical structure represented by General formula (1), or the said ferroelectric liquid crystal compound.

[In General Formula (1), X represents an aromatic ring or a linked aromatic ring which may have a substituent, and R ¹ represents an alkyl group having 1 to 24 carbon atoms which may have a substituent. Or an alkenyl group having 2 to 24 carbon atoms, wherein R ² is an optionally substituted alkyl group having 1 to 6 carbon atoms or —COR ′ (R ′ is an optionally substituted carbon). R ³ represents an alkyl group having 1 to 13 carbon atoms which may have a substituent. ]

  According to the present invention, a compound having an asymmetric carbon and exhibiting liquid crystallinity can be obtained by utilizing an environmentally friendly enzyme reaction that is friendly to humans, and a novel ferroelectric liquid crystal compound can be provided.

  Hereinafter, the present invention will be described. However, the present invention is not limited to the following embodiments, and can be arbitrarily modified and implemented.

  The present invention is a ferroelectric liquid crystal compound containing an asymmetric carbon atom, wherein the asymmetric carbon atom is introduced using an enzymatic reaction. Enzymatic reactions can be used not only to put a burden on the environment, but also to utilize the high substrate specificity and stereoselectivity of enzymatic reactions, to obtain high-purity optical isomers, and high performance and strength. A dielectric liquid crystal compound can be obtained efficiently.

  According to the present invention, it is possible to suitably obtain a compound having a large diastereomer ratio (hereinafter sometimes abbreviated as “% de”). In the present invention, “% de” is not particularly limited as long as it is sufficiently large to exhibit liquid crystallinity, but is preferably 70 or more, particularly preferably 80 or more, and further preferably 90 or more. Here, “% de” is defined as a value measured by the method described in the examples and measured in such a manner.

［一般式（１）中、Ｘは置換基を有していてもよい芳香族環又は連結芳香族環を示し、Ｒ^１は置換基を有していてもよい炭素数１〜２４のアルキル基又は炭素数２〜２４のアルケニル基を示し、Ｒ^２は置換基を有していてもよい炭素数１〜６のアルキル基又は−ＣＯＲ'（Ｒ'は置換基を有していてもよい炭素数１〜６のアルキル基又はフェニル基を示す）を示し、Ｒ^３は置換基を有していてもよい炭素数１〜１３のアルキル基を示す。］ The specific chemical structure of the ferroelectric liquid crystal compound is not particularly limited as long as the asymmetric carbon atom present in the ferroelectric liquid crystal compound is introduced by an enzymatic reaction, but the following general formula ( A compound having the chemical structure represented by 1) is preferred.

[In General Formula (1), X represents an aromatic ring or a linked aromatic ring which may have a substituent, and R ¹ represents an alkyl group having 1 to 24 carbon atoms which may have a substituent. Or an alkenyl group having 2 to 24 carbon atoms, wherein R ² is an optionally substituted alkyl group having 1 to 6 carbon atoms or —COR ′ (R ′ is an optionally substituted carbon). R ³ represents an alkyl group having 1 to 13 carbon atoms which may have a substituent. ]

  In general formula (1), X is an aromatic ring or a linked aromatic ring which may have a substituent. A linked aromatic ring refers to one in which one or more aromatic rings are directly bonded by a single bond. Here, the aromatic ring or “one aromatic ring included in the linked aromatic ring” is not particularly limited, but is a condensed hydrocarbon ring such as a benzene ring, naphthalene ring, anthracene ring, phenanthrene ring, pyrene ring; Nitrogen-containing aromatic heterocycles such as pyrrole ring, imidazole ring, pyrazole ring, pyridine ring, pyrimidine ring, purine ring, quinoline ring, and carbazole ring; oxygen or sulfur-containing aromatics such as furan ring, thiophene ring, oxazole ring, and thiazole ring Group heterocycle and the like.

  The aromatic ring or “one aromatic ring included in the linked aromatic ring” is particularly preferably a benzene ring or a pyrimidine ring. Examples of the linked aromatic ring include those in which these aromatic rings are bonded by a single bond, that is, a biphenyl ring, a phenylpyrimidine ring, a bipyrimidine ring, and the like.

  X may have a substituent, but the substituent is not particularly limited. For example, a lower alkyl group such as a methyl group or an ethyl group; a hydroxyl group; a lower alkoxyl group such as a methoxyl group or an ethoxyl group; fluorine, Halogen groups such as chlorine; methoxymethyl group, methoxyethoxymethyl group and the like.

In general formula (1), R ¹ is an alkyl group having 1 to 24 carbon atoms which may have a substituent, or an alkenyl group having 2 to 24 carbon atoms which may have a substituent. It is. The number of carbon atoms is preferably 12-22, particularly preferably 14-20. When R ¹ is an alkenyl group, the number of double bonds is preferably 1 to 5 and particularly preferably 1 to 3 from the viewpoint of easy liquid crystallinity.

The substituent in R ¹ is not particularly limited as long as it does not exhibit liquid crystallinity, but ricinoleic acid using castor oil as a raw material may have a hydroxyl group as described below, and is derived from the hydroxyl group or the hydroxyl group. Substituents such as alkyloxy groups, aryloxy groups and ester groups are preferred.

The ferroelectric liquid crystal compound of the present invention is synthesized from castor oil or a castor oil derivative as a raw material, particularly in that it does not give an environmental load, is inexpensive, and is susceptible to an enzymatic reaction. preferable. Castor oil is a tricarboxylic acid ester of glycerol, and the carboxylic acid is mainly composed of ricinoleic acid (12-hydroxy-9-octadecenoic acid). Accordingly, R ¹ is carboxylated from ricinoleic acid (12-hydroxy-9-octadecenoic acid), that is, “— (CH ₂ ) ₇ CH═CHCH ₂ CH (OH) (CH ₂ ) ₅ CH ₃ ”. It is particularly preferred. It is also preferable to use ricinoleic acid hydride (12-hydroxyoctadecanoic acid) as a raw material, so that R ¹ is a carboxyl taken from ricinoleic acid hydride (12-hydroxyoctadecanoic acid), that is, “— (CH _{2) 10 CH (OH) (} CH 2) 5 that CH ₃ "is also particularly preferred.

In general formula (1), R ² is
(A) an optionally substituted alkyl group having 1 to 6 carbon atoms, or
(B) —COR ′ (R ′ represents an optionally substituted alkyl group having 1 to 6 carbon atoms, or an optionally substituted phenyl group)
It is.
When R ² is the above (a) or (b), an optical isomer having a large diastereomeric ratio (% de) can be obtained in a high yield by an enzymatic reaction using an enzyme such as lipase.

  (A) The alkyl group having 1 to 6 carbon atoms which may have a substituent is not particularly limited, but is preferably a methyl group, an ethyl group, a propyl group, or the like, and the methyl group is reactive. Particularly preferred in terms. As the substituent for the alkyl group, methoxyl group, ethoxyl group, benzyloxy group, vinyl group, phenyl group, methoxyethoxyl group, etc. are optical isomers having a large diastereomeric ratio (% de) by enzymatic reaction. This is particularly preferable in that it can be obtained in a high yield.

  The above “optionally substituted alkyl group having 1 to 6 carbon atoms” is a methyl group, and the substituent is a methoxyl group, an ethoxyl group, a benzyloxy group, a vinyl group, a phenyl group or a methoxy group. More preferred are those which are ethoxyl groups, that is, those corresponding to methoxymethyl group, ethoxymethyl group, benzyloxymethyl group, allyl group or benzyl group, respectively.

  (B) -COR 'is particularly limited as long as R' is an alkyl group having 1 to 6 carbon atoms which may have a substituent or a phenyl group which may have a substituent. However, as the alkyl group, a methyl group, an ethyl group, a propyl group, or the like is preferable because a high-purity optical isomer can be obtained in a high yield by an enzymatic reaction. These substituents are not particularly limited, and examples thereof include lower alkyl groups such as a methyl group and an ethyl group; halogen groups such as fluorine and chlorine. (B) -COR 'is particularly preferably an acetyl group, a benzoyl group or the like.

In general formula (1), R ³ is an optionally substituted alkyl group having 1 to 13 carbon atoms, but is an alkyl group having 3 to 9 carbon atoms. An alkyl group having 5 to 7 carbon atoms is particularly preferable.

  The method for synthesizing the compound represented by the general formula (1) is not particularly limited as long as an asymmetric carbon atom can be introduced using an enzymatic reaction. In addition, the synthesis methods specifically described in Examples described later are particularly preferable. Furthermore, a synthesis method within a range not departing from the gist of the synthesis reaction suggested in the examples, a synthesis method obtained by modifying the synthesis methods described in the examples, and the like are also preferable. In particular, the compound in which an asymmetric carbon atom is introduced using an enzyme reaction is represented by the general formula (2), which indicates that high-purity optical isomerism is achieved by an enzyme reaction using an enzyme such as lipase. The body is preferred because it is obtained in high yield.

［一般式（２）中、Ｒ^１は置換基を有していてもよい炭素数１〜２４のアルキル基又は炭素数２〜２４のアルケニル基を示し、Ｒ^２は置換基を有していてもよい炭素数１〜６のアルキル基又は−ＣＯＲ'（Ｒ'は置換基を有していてもよい炭素数１〜６のアルキル基又はフェニル基を示す）を示す。］

[In General Formula (2), R ¹ represents an optionally substituted alkyl group having 1 to 24 carbon atoms or an alkenyl group having ² to 24 carbon atoms, and R ² has a substituent group. Or an alkyl group having 1 to 6 carbon atoms or —COR ′ (R ′ represents an optionally substituted alkyl group or phenyl group having 1 to 6 carbon atoms). ]

By the enzymatic reaction using lipase or the like, for example, the following reaction formula (3) proceeds, and the compound (“1-MAG” in the reaction formula (3) (1 Monoacylglycerol)) is obtained as a highly pure optical isomer.

Here, R ¹ and R ² in the general formula (2) and the reaction formula (3) are the same as those in the general formula (1) described above, and preferred ranges and the like are also the same.

"1, 3-DAG" in the reaction formula (3) (1,3-diacylglycerol) is a tricarboxylic acid ester of glycerol, according to a conventional method, generally obtained by substituting -OCOR ¹ to -OR ² is It is a compound that does not show optical activity.

  In this case, the above-mentioned “tricarboxylic acid ester of glycerol” is a triricinoleic acid glyceride shown below, which is the main component of castor oil, which is used for paints, lubricants, pharmaceuticals, cosmetics, etc. It is particularly preferred because it is an important industrial material. Further, it is particularly preferable in that it has a high viscosity, a high hydroxyl value, is hardly soluble in petroleum solvents, is easily soluble in ether solvents, and can be obtained with high purity. In addition, in the following formula, a hydride obtained by adding hydrogen to a carbon-carbon double bond, and a compound in which a hydroxyl group is made another substituent by adding a reaction to the hydroxyl group in the following formula are also described in the above-mentioned “glycerol tricarboxylic acid”. The “acid ester” is preferable for the same reason.

  The enzyme used in the reaction formula (3) is not particularly limited, but lipase is preferable in that hydrolysis and esterification can be performed without using a special apparatus at normal temperature and pressure. The lipase is not particularly limited as long as it can easily introduce an asymmetric carbon atom, but lipase PS derived from Pseudomonas cepacia, lipase AK derived from Pseudomonas fluorescens, pig Preferred examples include lipase PPL derived from pancreas (Porcine pancreas), lipase CAL derived from Candida antarctica, lipase AY derived from Candida rugosa, and the like. Among them, lipase PS derived from Pseudomonas cepacia or lipase AK derived from Pseudomonas fluorescens has a high hydrolysis rate and high diastereoselectivity. Is particularly preferable.

The enzyme reaction is preferably performed using, for example, the above-described enzyme or the like and the compound represented by the general formula (2) in an organic solvent-phosphate buffer solution in an air atmosphere. At this time, when R ² is in the above-described range, 1-MAG showing optical activity is efficiently produced in the reaction formula (3).

R ³ —O—X—COOH (wherein R ³ and X are the same as those in the general formula (1)) are reacted with the hydroxyl group of 1-MAG according to a conventional method to give a general formula (1) The compounds shown can be obtained.

  The reason why the compound represented by the general formula (1) can be used as a ferroelectric liquid crystal compound is described below, but the present invention is not limited to the following reason. Moreover, it is not limited to the following compound examples.

That is, the following structure represents a general ferroelectric liquid crystal structure. Most of the compounds exhibiting liquid crystallinity are low molecular organic compounds and have a long and thin three-dimensional structure. The compound represented by the left-right asymmetric general formula (1) is considered to have been able to be a ferroelectric liquid crystal compound because it is similar to the following structure.

In the above structure, the terminal group is a relatively flexible part (R ¹ and R ³ in the general formula (1)), which corresponds to a fatty chain part of 1-monoacylglycerol (1-MAG) and the like. is doing. A polar group is a functional group having an electron bias, and corresponds to a carbonyl group. Furthermore, the compound represented by the general formula (1) has an asymmetric carbon. That is, a compound derived from triacylglycerol, such as castor oil, is converted into 1-monoacylglycerol (1-MAG) by an enzymatic reaction to become a fragment having an asymmetric carbon of a ferroelectric liquid crystal, and the remaining ring It is considered that a ferroelectric liquid crystal compound could be obtained by introducing a structural portion.

  As described above, as a method for obtaining 1-monoacylglycerol (1-MAG) with high stereoselectivity, hydrolysis or acyl rearrangement using an enzyme such as lipase, which is an environmentally friendly method, is performed by an easy experimental operation. A ferroelectric liquid crystal compound could be obtained.

  Hereinafter, the present invention will be described more specifically with reference to examples and comparative examples. However, the present invention is not limited to these examples as long as the gist thereof is not exceeded.

<Method for measuring NMR spectrum and infrared absorption spectrum>
The NMR spectrum was measured according to a conventional method using α-500 EX-270 manufactured by JEOL Ltd. and tetramethylsilane (TMS) as an internal standard. The infrared absorption spectrum was measured according to a conventional method using FT / IR-460 manufactured by JASCO Corporation.

<Measurement method of specific rotation ([α] _D ²⁶ )>
Specific rotation ([α] _D ²⁶ ) was measured according to a conventional method using a polarimeter, P-1020 manufactured by JASCO Corporation.

<Diastereomeric ratio (% de) determination method>
The method for determining the diastereomeric ratio (% de) of all the compounds was determined by measuring a derivative in which all the hydroxyl groups of the product were benzoylated using high performance liquid chromatography. The high performance liquid chromatography was measured with a developing solvent (hexane: 2-propanol = 70: 1) using a L-400UV Detector L-600 Pump manufactured by Hitachi, Ltd. and a CHIRALCEL OD manufactured by Daicel Chemical.

<Preparation of raw materials, solvents, etc.>
Triricinoleic acid glyceride was obtained by purifying castor oil manufactured by Ito Oil Co., Ltd. with a developing solvent (hexane: ethyl acetate = 4: 1) using silica gel column chromatography to obtain pure triricinoleic acid glyceride. Tetrahydrofuran (THF) was distilled from sodium benzophenone ketyl immediately before use, and 1,4-dioxane was heated and refluxed in the presence of calcium hydride after pre-dried with calcium hydride, and then distilled. used. As other reagents, commercially available products were distilled or used as they were. For purification using column chromatography, silica gel 60N (spherical, neutral) manufactured by Kanto Chemical Co., Inc. was used for purification, and for purification using thin layer chromatography, a material carrying Merck Kisel Gel PF254 was used. All reactions were conducted under a stream of argon except under special circumstances, the reaction vessel was capped with a septum, and anhydrous solvents and mixtures were transferred using a dry syringe.

1. Synthetic raw material synthesis example 1
<Synthesis of 1,3-di-12-hydroxy -cis-9-Okutade cell noil glycerol>
Glycerol (368.4 mg, 4.0 mmol) and 4-dimethylaminopyridine (390.9 mg, 3.2 mmol) were weighed and added to a 50 mL two-necked eggplant flask, and purged with argon. Dichloromethane (2.0 mL) was added, dichloromethane (2.0 mL) was added to ricinoleic acid (1193.8 mg, 4.0 mmol) and added dropwise to the reaction system, and the mixture was washed with dichloromethane (2.0 mL). The addition to the reaction system was repeated twice.

  After stirring at 0 ° C. for 5 minutes, dichloromethane (2.0 mL) was added to 1,3-dicyclohexylcarbodiimide (990.4 mg, 4.8 mmol), and the mixture was added dropwise to the reaction system, and washed once more with dichloromethane (2.0 mL). The washing solution was added to the reaction system and stirred for 16 hours, and then filtered through Celite using ethyl acetate, and the filtrate was washed with 0.5 M hydrochloric acid and dried over anhydrous sodium sulfate. The filtrate filtered with a cotton plug was concentrated by an evaporator to obtain a crude product.

収率 ：２７％ （７１２．６ｍｇ）
Ｒｆ値：０．６（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状 The resulting crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 5: 1) to give the 1,3-di-12-hydroxy -cis-9-Okutade cell noil glycerol below.

Yield: 27% (712.6 mg)
Rf value: 0.6 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.82-0.92 (m, 6H), 1.20-1.40 (m, 32H), 1.40-1.52 (m, 4H), 1.52-1.61 (m, 7H), 2.00- 2.13 (m, 4H), 2.14-2.25 (m, 4H), 2.33 (t, J = 7.4Hz, 4H), 3.55-3.69 (m, 2H), 4.03-4.29 (m, 5H), 5.33-5.48 ( m, 2H), 5.48-5.65 (m, 2H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 14.0, 14.1, 22.5, 24.7, 25.6, 27.2, 28.9, 29.2, 31.7, 34.0, 35.2, 36.7, 64.9, 67.9, 71.4, 76.5, 77.0, 77.5, 125.2.133.0.173.6.173.7

Raw material synthesis example 2
<Synthesis of 1,3-di-12-hydroxy -cis-9-Okutade cell noil -2-O-methoxymethyl-glycerol>
Raw material synthesis example 2- (1)
[Synthesis of 2-O-methoxymethyl-1,3-benzylideneglycerol]
1,3-benzylideneglycerol (3.63 g, 19.8 mmol) was weighed and added to a 50 mL two-necked eggplant flask and purged with argon. Dichloromethane (10.0 mL) was added followed by diisopropylethylamine (10.3 mL, 59.3 mmol). Methyl chloromethyl ether (5.5 mL, 59.3 mmol) was added dropwise to the reaction system and stirred at room temperature for 19 hours, and then the reaction was stopped by adding 1 M hydrochloric acid. Extracted with dichloromethane and dried over sodium sulfate. The filtrate filtered with a cotton plug was concentrated by an evaporator to obtain a crude product.

収率 ：４２％（１．８６ｇ）
Ｒｆ値：０．５（ヘキサン：酢酸エチル＝１：１）
形状 ：白色粉末結晶 The obtained crude product was purified by recrystallization (hexane: benzene = 4: 3) to obtain the following 2-O-methoxymethyl-1,3-benzylideneglycerol.

Yield: 42% (1.86 g)
Rf value: 0.5 (hexane: ethyl acetate = 1: 1)
Shape: White powder crystal

¹ H NMR (270 MHz, CDCl ₃ ): δ 3.45 (s, 3H), 3.60-3.61 (m, 1H), 4.13 (d, J = 1.3 Hz, 2H), 4.31 (d, J = 1.3 Hz, 2H ), 4.82 (s, 2H), 5.57 (s, 1H), 7.34-7.37 (m, 3H), 7.48-7.53 (m, 2H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 55.0, 67.6, 69.2, 94.5, 100.8, 125.8, 127.8, 128.5, 137.8

IR (CHCl ₃ ): 2955, 1454, 1388, 1215, 1143, 1036, 745 cm ^-1

Raw material synthesis example 2- (2)
[Synthesis of 2-O-methoxymethylglycerol]
To a 50 mL two-necked eggplant flask, 2-O-methoxymethyl-1,3-benzylideneglycerol (547.3 mg, 2.44 mmol) obtained in Raw Material Synthesis Example 2- (1) was weighed and added. 10% palladium-carbon (542.4 mg, 0.49 mmol) and methanol (5.0 mL) were added to perform hydrogen replacement. After stirring for 13 hours at room temperature, 10% palladium-carbon was removed by celite filtration, the reaction was stopped, and the following 2-O-methoxymethylglycerol was obtained by concentrating with an evaporator.

収率 ：９４％（３１３．５ｍｇ）
Ｒｆ値：０．２（ジクロロメタン：メタノール＝９：１）
形状 ：無色オイル状

Yield: 94% (313.5 mg)
Rf value: 0.2 (dichloromethane: methanol = 9: 1)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 3.12 (brs, 1H), 3.45 (s, 3H), 3.61-3.75 (m, 5H), 4.77 (s, 2H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 55.6, 62.5, 80.9, 96.6

IR (CHCl ₃ ): 3415, 2944, 1647, 1455, 1036, 910,618 cm ⁻¹

Raw material synthesis example 2- (3)
Synthesis of 1,3-di-12-hydroxy -cis-9-Okutade cell noil -2-O-methoxymethyl glycerol]
In a 50 mL two-necked eggplant flask, 2-O-methoxymethylglycerol (800.3 mg, 5.90 mmol) obtained in Raw Material Synthesis Example 2- (2) and 4-dimethylaminopyridine (1441.6 mg, 11.8 mmol) were prepared. ) Was weighed and added to replace with argon. Dichloromethane (2.0 mL) was added to ricinoleic acid (4210.5 mg, 14.11 mmol) and added dropwise to the reaction system, then washed with dichloromethane (1.5 mL), and the washing solution was added to the reaction system twice. It was.

  After stirring at 0 ° C. for 5 minutes, dichloromethane (2.0 mL) was added to 1,3-dicyclohexylcarbodiimide (4669.4 mg, 23.6 mmol), and the mixture was added dropwise to the reaction system, and washed once more with dichloromethane (2.0 mL). The washing solution was added to the reaction system and stirred for 16 hours. Thereafter, the mixture was filtered through Celite using ethyl acetate, and the filtrate was washed with 0.5 M hydrochloric acid and dried over anhydrous sodium sulfate. The filtrate filtered with a cotton plug was concentrated by an evaporator to obtain a crude product.

収率 ：５２％（２１２９．３ｍｇ）
Ｒｆ値：０．７（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状 The resulting crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 5: 1) to give 1,3-di-12-hydroxy -cis-9-Okutade cell noil -2-O-following Methoxymethylglycerol was obtained.

Yield: 52% (2219.3 mg)
Rf value: 0.7 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.85-0.96 (m, 6H), 1.20-1.40 (m, 32H), 1.40-1.52 (m, 4H), 1.52-1.61 (m, 6H), 2.00- 2.13 (m, 4H), 2.20 (m, 4H), 2.33 (t, J = 7.4Hz, 4H), 3.40 (s, 3H), 3.55-3.69 (m, 2H), 4.01 (t, J = 5.0Hz , 1H), 4.11-4.17 (m, 2H), 4.20-4.26 (m, 2H), 4.71 (s, 2H), 5.38-5.51 (m, 2H), 5.53-5.60 (m, 2H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 13.7, 13.8, 20.6, 22.3, 24.5, 25.4, 27.0, 28.7, 28.8, 29.1, 29.2, 31.5, 33.7, 35.0, 36.5, 55.1, 60.0, 63.0, 71.0,72.2,95.5,125.2,132.3

IR (neat): 2926,1739,1540,1037,677,441cm ^-1

Raw material synthesis example 3
<Synthesis of 1,3-di-12-hydroxy -cis-9-Okutade cell noil -2-O-benzyloxymethyl glycerol>
Raw Material Synthesis Example 3- (1)
[Synthesis of 1,3-di-O-tert-butyldimethylsilylglycerol]
Glycerol (1668.4 mg, 18 mmol) and dimethylaminopyridine (3518.4 mg, 28.8 mmol) were weighed and added to a 100 mL two-necked eggplant flask and purged with argon. Dichloromethane (18 mL) was added followed by triethylamine (5.1 mL). Dichloromethane (8 mL) was added to tert-butyldimethylsilyl chloride (5426.3 mg, 36.0 mmol), added dropwise to the reaction system, washed with dichloromethane (5 mL), and adding the washing solution to the reaction system was repeated twice. . After stirring for 16 hours, the reaction was stopped by adding water. After extraction with diethyl ether, the collected organic layer was washed with water and a saturated aqueous solution of ammonium chloride and dried over anhydrous sodium sulfate. The filtrate filtered with a cotton plug was concentrated by an evaporator to obtain a crude product.

収率 ：７７％（４４４０．０ｍｇ） 分子式：Ｃ_１５Ｈ_３６Ｏ_３Ｓｉ_２
Ｒｆ値：０．３２（ヘキサン：酢酸エチル＝３：１）
形状 ：無色オイル状 The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 15: 1) to obtain the following 1,3-di-O-tert-butyldimethylsilylglycerol.

Yield: 77% (4440.0 mg) Molecular formula: C ₁₅ H ₃₆ O ₃ Si ₂
Rf value: 0.32 (hexane: ethyl acetate = 3: 1)
Shape: colorless oil

The above is known in the literature and was synthesized according to the following literature.
References: JMChong, KKSokoll, Tetrahedoron Lett., 33, 879 (1992).

Raw Material Synthesis Example 3- (2)
[Synthesis of 1,3-di-O-tert-butyl-2-O-benzyloxymethylglycerol]
To a 50 mL two-necked eggplant flask, 1,3-di-O-tert-butyldimethylsilylglycerol (774.5 mg, 2.40 mmol) obtained in Raw Material Synthesis Example 3- (1) was weighed and added, and purged with argon. Did. Dichloromethane (10 mL) was added, the mixture was stirred at 0 ° C. for 5 minutes, and diisopropylethylamine (0.52 mL) was added. Benzyl chloromethyl ether (0.4 mL) was added and stirred for 5 minutes, then returned to room temperature and stirred for 14 hours. The reaction was stopped by adding water and extracted with diethyl ether. The collected organic layer was washed with water and saturated aqueous ammonium chloride solution and dried over anhydrous sodium sulfate. The filtrate filtered with a cotton plug was concentrated by an evaporator to obtain a crude product.

収率 ：８３％（８８０．７ｍｇ） 分子式：Ｃ_２３Ｈ_４４Ｏ_４Ｓｉ_２
Ｒｆ値：０．６（ヘキサン：酢酸エチル＝３：１）
形状 ：無色オイル状 The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 25: 1) to obtain the following 1,3-di-O-tert-butyl-2-O-benzyloxymethylglycerol. .

Yield: 83% (880.7mg) Molecular _{formula: C 23 H 44 O 4 Si} 2
Rf value: 0.6 (hexane: ethyl acetate = 3: 1)
Shape: colorless oil

The above is known in the literature and was synthesized according to the following literature.
References: JM Chong, KKSokoll, Tetrahedoron Lett., 33, 879 (1992).

Raw Material Synthesis Example 3- (3)
[Synthesis of 2-O-benzyloxymethylglycerol]
In a 50 mL two-necked eggplant flask, 1,3-di-O-tert-butyl-2-O-benzyloxymethylglycerol (1432.5 mg, 3.25 mmol) obtained in Raw Material Synthesis Example 3- (2) was added. Weighed and added, and replaced with argon. 1M tetrabutylammonium fluoride in THF (13 mL, 13 mmol) was added and stirred for 3 hours. The reaction was stopped by adding water, extracted twice with ethyl acetate, diethyl ether, and chloroform, washed with a saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. The filtrate filtered with a cotton plug was concentrated by an evaporator to obtain a crude product.

収率 ：４８％（３３６．６ｍｇ） 分子式：Ｃ_１１Ｈ_１６Ｏ_４
Ｒｆ値：０．１（ヘキサン：酢酸エチル＝１：２）
形状 ：無色オイル状 The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1) to obtain the following 2-O-benzyloxymethylglycerol.

Yield: 48% (336.6 mg) Molecular formula: C ₁₁ H ₁₆ O ₄
Rf value: 0.1 (hexane: ethyl acetate = 1: 2)
Shape: colorless oil

The above is known in the literature and was synthesized according to the following literature.
References: JMChong, KKSokoll, Tetrahedoron Lett., 33, 879 (1992).

Raw Material Synthesis Example 3- (4)
Synthesis of 1,3-di-12-hydroxy -cis-9-Okutade cell noil -2-O-benzyloxymethyl glycerol]
In a 30 mL two-necked eggplant flask, 2-O-benzyloxymethylglycerol (61.9 mg, 0.29 mmol) obtained in the raw material synthesis example 3- (3) and 4-dimethylaminopyridine (57.0 mg, 0. 47 mmol) was weighed and added to replace with argon. Dichloromethane (0.5 mL) was added to ricinoleic acid (348.1 mg, 1.17 mmol), added dropwise to the reaction system, washed with dichloromethane (0.5 mL), and adding the washing solution to the reaction system was repeated twice.

  Next, after stirring at 0 ° C. for 5 minutes, dichloromethane (0.5 mL) was added to 1,3-dicyclohexylcarbodiimide (150.6 mg, 0.73 mg) and added dropwise to the reaction system, and dichloromethane (1.0 mL) was added again. The solution was added to the reaction system, stirred for 17 hours, filtered through Celite using ethyl acetate, and the filtrate was washed with 0.5 M hydrochloric acid and dried over anhydrous sodium sulfate. The filtrate filtered with a cotton plug was concentrated by an evaporator to obtain a crude product.

収率 ：７０％（１５８．８ｍｇ）
Ｒｆ値：０．７（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状 The resulting crude product by thin layer chromatography (hexane: ethyl acetate = 2: 1) to give the following 1,3-di-12-hydroxy -cis-9-Okutade cell noil-2-O-benzyl Oxymethylglycerol was obtained.

Yield: 70% (158.8 mg)
Rf value: 0.7 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.85-0.96 (m, 6H), 1.20-1.40 (m, 34H), 1.40-1.52 (m, 4H), 1.52-1.68 (m, 4H), 2.00- 2.13 (m, 4H), 2.17-2.25 (m, 4H), 2.30 (t, J = 7.6Hz, 4H), 3.55-3.69 (m, 2H), 4.08-4.30 (m, 5H), 4.65 (s, 2H), 4.85 (s, 2H), 5.33-5.48 (m, 2H), 5.49-5.61 (m, 2H), 7.24-7.40 (m, 5H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 14.0, 22.6, 24.8, 25.7, 27.3, 29.0, 29.3, 29.5, 31.8, 34.0, 35.3, 36.8, 63.2, 69.5, 71.4, 72.5, 93.7, 125.2, 127.7,128.4,133.2,137.5,173.4

IR (neat): 3446,2927,1737,1454,1172,1039,733cm ^-1

2. Enzyme reaction Using the raw materials synthesized above, the compounds shown in Tables 1 to 4 below were synthesized by the reactions shown in Tables 1 to 4.

表２中、「ＢＯＭ」はベンジルオキシメチル基を示し、「ＭＯＭ」はメトキシメチル基を示す。

In Table 2, “BOM” represents a benzyloxymethyl group, and “MOM” represents a methoxymethyl group.

「Ｂｎ」はベンジル基を示す。

“Bn” represents a benzyl group.

「Ｂｎ」はベンジル基を示す。

“Bn” represents a benzyl group.

  The compounds shown in Tables 1 to 4 above were synthesized using enzymes as follows. Specific synthesis methods of representative ones of the compounds shown in Tables 1 to 4 are shown below.

Enzyme reaction example 1
<Synthesis of 1-mono-12-hydroxy -cis-9-Okutade cell noil glycerol>
(Synthesis of Entry 1 in Table 1)
Air atmosphere, in a two-neck eggplant flask 30 mL, obtained in Starting Material Synthesis Example 1 1,3-12-hydroxy -cis-9-Okutade cell decanoyl glycerol (43.7 mg, 0.067 mmol) were weighed Then, THF (0.4 mL) and a phosphate buffer solution (1.2 mL) were added. Lipase PS (4.0 mg) manufactured by Amano Enzyme Inc. was weighed and added to the reaction system, and then stirred at room temperature for 20 minutes. The reaction was stopped by removing the enzyme by celite filtration with ethyl acetate using a glass funnel. The filtrate was washed with brine and concentrated with an evaporator to obtain a crude product.

収率 ：２６％（６．４ｍｇ）
Ｒｆ値：０．７（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状 The resulting crude product was purified by column chromatography (hexane: ethyl acetate = 5: 1) to give the Entry1 in Table 1, i.e., to obtain a 1-12- hydroxy -cis-9-Okutade cell noil glycerol follows It was.

Yield: 26% (6.4 mg)
Rf value: 0.7 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.82-0.96 (m, 3H), 1.22-1.40 (m, 16H), 1.42-1.53 (m, 2H), 1.53-1.90 (m, 4H), 2.00- 2.13 (m, 2H), 2.17-2.26 (m, 2H), 2.33 (t, J = 7.4Hz, 2H), 3.51-3.71 (m, 3H), 3.83-3.97 (m, 1H), 4.12-4.25 ( m, 2H), 5.36-5.45 (m, 1H), 5.48-5.58 (m, 1H)

Measurement example 1
Measurement of diastereomeric ratio (% de) of the compound obtained in Enzyme Reaction Example 1 (compound of Entry 1 in Table 1) <1,2-O-dibenzoyl-3-mono-12-benzyloxy-cis-9- synthesis of Okutade cell noil glycerol>
(Benzoylation of 1-mono-12-hydroxy -cis-9-Okutade cell decanoyl glycerol (compound of Entry1 in Table 1))
Two-necked eggplant flask 30 mL, obtained in the enzymatic reaction Example 1 1-mono-12-hydroxy -cis-9-Okutade cell decanoyl glycerol (compound of Entry1 in Table 1) a (4.4 mg, 0.012 mmol) Weighed and added argon. Dichloromethane (1.5 mL) and pyridine (0.02 mL, 0.26 mmol) were added, the mixture was stirred at 0 ° C. for 5 minutes, and then benzoyl chloride (0.04 mL, 0.24 mmol) was added dropwise. After stirring at room temperature for 13.5 hours, the reaction was quenched with 2M hydrochloric acid.

  The mixture was extracted with ethyl acetate, and the collected organic layer was washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The filtrate filtered through a cotton plug was concentrated with an evaporator to obtain a crude product.

収率 ：９４％（７．６ｍｇ）
Ｒｆ値：０．８（ヘキサン：酢酸エチル＝１：２）
形状 ：無色オイル状 The obtained crude product was purified by thin layer chromatography (hexane: ethyl acetate = 9: 1), and further purified by thin layer chromatography (hexane: ethyl acetate = 1: 1). It was obtained O- dibenzoyl-3-mono-12-benzyloxy--cis-9-Okutade cell noil glycerol. Its diastereomeric ratio (% de) was 28%. From this, it was found that the diastereomer ratio (% de) of the compound obtained in Enzyme Reaction Example 1 (the compound of Entry 1 in Table 1) was 28% as shown in Table 1.

Yield: 94% (7.6 mg)
Rf value: 0.8 (hexane: ethyl acetate = 1: 2)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.86 (t, J = 6.6 Hz, 3H), 1.16-1.41 (m, 16H), 1.52-1.73 (m, 4H), 1.93-2.08 (m, 2H) , 2.31 (t, J = 7.6Hz, 2H), 2.42 (dd, J = 6.1,11.7Hz, 2H), 4.41-4.71 (m, 4H), 5.09-5.18 (m, 1H), 5.37-5.451 (m , 2H), 5.57-5.75 (m, 1H), 7.39-7.45 (m, 6H), 7.51-7.59 (m, 3H), 8.01-8.05 (m, 6H)

  In Enzyme Reaction Example 1, Entry 2 to 4 in Table 1 were synthesized in the same manner as in Enzyme Reaction Example 1 except that the conditions shown in Entry 2 to 4 in Table 1 were used instead of Entry 1 in Table 1. Moreover, it carried out similarly to the measurement example 1, and obtained the diastereomeric ratio (% de) of the compound shown to Entry2-4 of Table 1 by benzoylating and measuring diastereomeric ratio (% de). The results are summarized in Table 1.

Enzyme reaction example 2
<Synthesis of 1-mono-12-hydroxy -cis-9-Okutade cell noil -2-O-benzyloxymethyl glycerol>
(Synthesis of Entry 1 in Table 2)
Air atmosphere, in a two-neck eggplant flask 30 mL, Starting Material Synthesis Example 3 (final Starting Material Synthesis Example 3- (4)) obtained in 1,3-12-hydroxy -cis-9-Okutade cell noil -2-O-benzyloxymethylglycerol (77.3 mg, 0.10 mmol) was weighed and added, and THF (0.5 mL) and phosphate buffer solution (1.5 mL) were added. Lipase AK (5.0 mg) was weighed and added to the reaction system, and then stirred at room temperature for 30 minutes. The reaction was stopped by removing the enzyme by celite filtration with ethyl acetate using a glass funnel. The filtrate was washed with brine and concentrated with an evaporator to obtain a crude product.

収率 ：１４％（６．８ｍｇ）
Ｒｆ値：０．５（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状
［α］_D ²⁶＝＋１３．７（ｃ０．０６８，ＣＨＣｌ₃）
ここで、「ｃ０．０６８」という表現は、物質濃度（溶質ｇ／溶液１００ｍＬ）を表し、以下同様である。ＣＨＣｌ₃は測定に用いた溶媒である。すなわちこの場合は、「（上記測定物質０．０６８ｇ）／（ＣＨＣｌ₃溶液１００ｍＬ）」を表す。 The resulting crude product by thin layer chromatography (hexane: ethyl acetate = 1: 1) to give the Entry1 in Table 2, i.e., the following 1-mono-12-hydroxy -cis-9-Okutade cell noil -2-O-benzyloxymethylglycerol was obtained.

Yield: 14% (6.8 mg)
Rf value: 0.5 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil [α] _D ²⁶ = + 13.7 (c 0.068, CHCl ₃ )
Here, the expression “c0.068” represents the substance concentration (solute g / 100 mL of solution), and so on. CHCl ₃ is the solvent used for the measurement. That is, in this case, “(the measurement substance 0.068 g) / (CHCl ₃ solution 100 mL)” is represented.

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.86-0.90 (m, 3H), 1.29-1.46 (m, 18H), 1.60-1.67 (m, 2H), 2.01-2.06 (m, 2H), 2.18- 2.23 (m, 2H), 2.28-2.34 (m, 2H), 2.58-2.63 (m, 1H), 3.61-3.70 (m, 3H), 3.89-3.92 (m, 1H), 4.15-4.25 (m, 2H ), 4.62-4.66 (m, 2H), 4.86-4.88 (m, 2H), 5.37-5.44 (m, 1H), 5.53-5.57 (m, 1H), 7.30-7.38 (m, 5H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 14.1, 22.6, 24.8, 25.3, 25.7, 27.3, 29.0, 29.3, 29.5, 31.8, 34.1, 35.3, 36.8, 62.5, 63.2, 70.0, 71.4, 76.5, 77.0,71.4,76.5,77.0,77.5,94.5,125.2,127.9,128.5,133.3,137.2,173.7

IR (neat): 3429,2928,2856,1739,1456,1171,1040,735,699cm ^-1

Measurement example 2
Measurement of diastereomeric ratio (% de) of the compound obtained in Enzyme Reaction Example 2 (the compound of Entry 1 in Table 2) <1-O-benzoyl-2-O-benzyloxymethyl-3-mono-12-benzyl synthesis of oxy -cis-9-Okutade cell noil glycerol>
(Benzoylation of 1-mono-12-hydroxy -cis-9-Okutade cell noil -2-O-benzyloxymethyl glycerol (compound of Entry1 in Table 2))
Two-necked eggplant flask 30 mL, obtained in the enzymatic reaction Example 2 1-mono-12-hydroxy -cis-9-Okutade cell decanoyl glycerol (compound of Entry1 in Table 2) (11.0 mg, 0.022 mmol) Weighed and added argon. Dichloromethane (1.5 mL) and pyridine (0.02 mL, 0.24 mmol) were added, the mixture was stirred at 0 ° C. for 5 minutes, and then benzoyl chloride (0.04 mL, 0.26 mmol) was added dropwise. After stirring at room temperature for 2 hours, the reaction was quenched with 2M hydrochloric acid. The mixture was extracted with ethyl acetate, and the collected organic layer was washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The filtrate filtered through a cotton plug was concentrated with an evaporator to obtain a crude product.

収率 ：６８％（１０．９ｍｇ）
Ｒｆ値：０．７５（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状
［α］_D ²⁶＝＋９．３２（ｃ０．０６８，ＣＨＣｌ₃） The obtained crude product was purified by thin layer chromatography (hexane: ethyl acetate = 9: 1) and further purified by thin layer chromatography (hexane: ethyl acetate = 1: 1). - to obtain a benzoyl -2-O-methoxymethyl-3-mono-12-benzyloxy--cis-9-Okutade cell noil glycerol. The diastereomer ratio (% de) thereof was 71%. From this, it was found that the diastereomer ratio (% de) of the compound obtained in Enzyme Reaction Example 1 (the compound of Entry 1 in Table 2) was 71% as shown in Table 2.

Yield: 68% (10.9 mg)
Rf value: 0.75 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil [α] _D ²⁶ = + 9.32 (c 0.068, CHCl ₃ )

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.86 (t, J = 6.6 Hz, 3H), 1.23-1.41 (m, 16H), 1.59-1.73 (m, 4H), 1.98-2.04 (m, 2H) , 2.30 (t, J = 7.6Hz, 2H), 2.42 (dd, J = 6.1,11.7Hz, 2H), 4.23-4.53 (m, 5H), 4.66 (s, 2H), 4.90 (s, 2H), 5.09-5.18 (m, 1H), 5.37-5.49 (m, 2H), 7.26-7.34 (m, 5H), 7.39-7.45 (m, 4H), 7.51-7.59 (m, 2H), 8.01-8.05 (m , 4H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 14.1, 22.6, 24.8, 25.4, 27.3, 29.1, 29.5, 31.7, 32.0, 33.7, 34.1, 63.3, 64.0, 69.7, 72.6, 73.1, 76.8, 77.0, 77.3,93.8,124.1,127.8,128.2,128.4,129.5,129.7,132.7,133.2,137.7,166.2,173.6

IR (neat): 2929,2855,1720,1452,1273,1174,1112,1027,712cm ^-1

  In Enzyme Reaction Example 2, Entry 2 to 4 in Table 2 were synthesized in the same manner as in Enzyme Reaction Example 2 except that the conditions shown in Entry 2 to 4 in Table 2 were used instead of Entry 1 in Table 2. Moreover, it carried out similarly to the measurement example 2, and obtained the diastereomeric ratio (% de) of the compound shown to Entry2-4 of Table 2 by benzoylating and measuring diastereomeric ratio (% de). The results are summarized in Table 2.

Enzyme reaction example 3
<Synthesis of 1-mono-12-hydroxy -cis-9-Okutade cell noil -2-O-methoxymethyl-glycerol>
(Synthesis of Entry5 in Table 2)
Air atmosphere, in a two-neck eggplant flask 30 mL, obtained in Starting Material Synthesis Example 2 (final Starting Material Synthesis Example 2- (3)) 1,3-di-12-hydroxy -cis-9-Okutade cell noil -2-O-methoxymethylglycerol (1186.2 mg, 1.70 mmol) was weighed and added, and THF (8.0 mL) and phosphate buffer solution (24.0 mL) were added. Lipase PS (101.6 mg) was weighed and added to the reaction system, and then stirred at room temperature for 25 minutes. The reaction was stopped by removing the enzyme by celite filtration with ethyl acetate using a glass funnel. The filtrate was washed with brine and concentrated with an evaporator to obtain a crude product.

収率 ：３２％（２２４．４ｍｇ）
Ｒｆ値：０．５（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状 The resulting crude product was purified by column chromatography (hexane: ethyl acetate = 4: 1) to give the Entry5 in Table 2, i.e., the following 1-mono-12-hydroxy -cis-9-Okutade cell noil - 2-O-methoxymethylglycerol was obtained.

Yield: 32% (224.4 mg)
Rf value: 0.5 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.82-0.96 (m, 3H), 1.22-1.40 (m, 17H), 1.42-1.53 (m, 2H), 1.53-1.70 (m, 2H), 2.00- 2.13 (m, 2H), 2.17-2.26 (m, 2H), 2.33 (t, J = 7.4Hz, 2H), 3.15 (brs, 1H), 3.41 (s, 3H), 3.58-3.71 (m, 2H) , 3.79-3.87 (m, 1H), 4.12-4.26 (m, 2H), 4.74 (s, 2H), 5.36-5.45 (m, 1H), 5.48-5.58 (m, 1H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 13.9, 14.0, 22.5, 24.7, 25.6, 27.2, 28.9, 29.0, 29.2, 29.4, 31.7, 34.0, 35.2, 36.7, 55.5, 62.3, 63.2, 71.4, 76.5,96.4,125.2,132.9,173.6

Measurement example 3
Measurement of diastereomer ratio (% de) of the compound obtained in Enzyme Reaction Example 3 (compound of Entry 5 in Table 2) <1-O-benzoyl-2-O-methoxymethyl-3-mono-12-benzyloxy synthesis of -cis-9-Okutade cell noil glycerol>
(Benzoylation of 1-mono-12-hydroxy -cis-9-Okutade cell noil -2-O-methoxymethyl-glycerol (compound of Entry5 in Table 2))
Two-necked eggplant flask 30 mL, obtained in the enzyme reaction Example 3 1-mono-12-hydroxy -cis-9-Okutade cell decanoyl glycerol (compound of Entry5 in Table 2) (2.7mg, 0.0065mmol) Weighed and added argon. Dichloromethane (1.5 mL) and pyridine (0.02 mL, 0.24 mmol) were added, the mixture was stirred at 0 ° C. for 5 minutes, and then benzoyl chloride (0.04 mL, 0.26 mmol) was added dropwise. After stirring at room temperature for 14 hours, the reaction was quenched with 2M hydrochloric acid. The mixture was extracted with ethyl acetate, and the collected organic layer was washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The filtrate filtered through a cotton plug was concentrated with an evaporator to obtain a crude product.

収率 ：９９％（４．０ｍｇ）
Ｒｆ値：０．６５（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状 The obtained crude product was purified by thin layer chromatography (hexane: ethyl acetate = 9: 1) and further purified by thin layer chromatography (hexane: ethyl acetate = 1: 1). - to obtain a benzoyl -2-O-methoxymethyl-3-mono-12-benzyloxy--cis-9-Okutade cell noil glycerol. Its diastereomeric ratio (% de) was 94%. From this, it was found that the diastereomer ratio (% de) of the compound obtained in Enzyme Reaction Example 3 (the compound of Entry5 in Table 2) was 94% as shown in Table 2.

Yield: 99% (4.0 mg)
Rf value: 0.65 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.86 (t, J = 6.6 Hz 3H), 1.26-1.38 (m, 16H), 1.59-1.70 (m, 4H), 2.01-2.05 (m, 2H), 2.33 (t, J = 7.6Hz2H), 2.43 (dd, J = 5.9,11.6Hz, 2H), 3.39 (s, 3H), 4.15-4.51 (m, 5H), 4.76 (s, 2H), 5.11-5.16 (m, 1H), 5.38-5.47 (m, 2H), 7.40-7.47 (m, 4H), 7.52-7.57 (m, 2H), 8.00-8.06 (m, 4H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 14.0, 22.5, 24.8, 25.4, 27.3, 29.0, 29.1, 29.2, 29.5, 31.7, 32.0, 33.7, 34.1, 55.6, 63.4, 64.0, 72.7, 74.6, 77.2,96.0,124.1,128.2,128.4,129.5,129.6,129.7,130.7,132.7,133.2,166.2,173.5

IR (neat): 2928,2856,1721,1602,1453,1273,1172,1111,1070,1031,921,712,447,418cm ^-1

  In enzyme reaction example 3, instead of entry 5 in table 2, entry 6 in table 2 was synthesized in the same manner as in enzyme reaction example 3 except that the conditions shown in entry 6 in table 2 were used. Moreover, it carried out similarly to the measurement example 3, and obtained the diastereomeric ratio (% de) of the compound shown to Entry6 of Table 2 by benzoylating and measuring a diastereomeric ratio (% de). The results are summarized in Table 2.

Enzyme reaction example 4
<Asymmetrication of 2-O-benzylglycerol with PPL using vinyl 12-hydroxyoctade-9-enoate as an acyl donor>
(Synthesis of Entry 1 in Table 3)
Vinyl 12-hydroxyoctade-9-enoate 1) (32.5 mg, 0.100 mmol) synthesized according to the method of the following document was weighed and added to a 30 mL two-necked eggplant flask, and the atmosphere was replaced with argon. Acetonitrile (0.5 mL) was added to 2-O-benzylglycerol (18.2 mg, 0.100 mmol), added dropwise to the reaction system, washed with acetonitrile (0.5 mL), and the washing solution was added to the reaction system. Repeated times. After stirring at 50 ° C. for 5 minutes, PPL (20.0 mg) was weighed and added directly to the reaction system. After stirring for 3.5 hours, celite was filtered using a glass funnel to remove the enzyme, and the celite was washed with ethyl acetate. The filtrate was concentrated with an evaporator to obtain a crude product.
C. Waldinger, M. Schneider, J. Am. Oil. Chem. Soc., 73, 1513 (1996)

収率 ：１５％（７．１ｍｇ）
Ｒｆ値：０．５８（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状 The resulting crude product by thin layer chromatography (hexane: ethyl acetate = 1: 2) to give the Entry1 in Table 3, namely, the following 1-mono 12-hydroxy -cis-9-Okutade cell noil - 2-O-benzylglycerol was obtained.

Yield: 15% (7.1 mg)
Rf value: 0.58 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.88 (t, J = 6.3 Hz, 3H), 1.23-1.30 (m, 16H), 1.43-1.49 (m, 2H), 1.59-1.64 (m, 3H) , 2.01-2.13 (m, 3H), 2.21 (t, J = 6.8Hz, 2H), 2.32 (t, J = 7.4Hz, 2H), 3.59-3.72 (m, 4H), 4.23-4.25 (m, 2H ), 4.58-4.74 (m, 2H), 5.38-5.58 (m, 2H), 7.30-7.36 (m, 5H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 173.8, 137.8, 133.3, 128.5, 128.0, 127.8, 125.2, 77.2, 72.1, 71.5, 62.6, 62.0, 36.8, 35.3, 34.2, 31.8, 29.5, 29.3, 29.1, 29.0, 29.0, 27.3, 25.7, 24.9, 22.6, 14.1

IR (neat): 3418,2927,2857,1736,1457,1178,1117,1060,737,699cm ^-1

Measurement example 4
Measurement of diastereomeric ratio (% de) of the compound obtained in Enzyme Reaction Example 4 (compound of Entry 1 in Table 3) <1-O-benzoyl-2-O-benzyl-3-mono-12-benzyloxy- the synthesis of cis-9- Okutade cell noil glycerol>
(Benzoylation of 1-mono 12-hydroxy -cis-9-Okutade cell noil -2-O-benzyl glycerol (compound of Entry1 in Table 3))
Obtained in the enzyme reaction Example 4 1-mono 12-hydroxy -cis-9-Okutade cell noil -2-O-benzyl glycerol (compound of Entry1 in Table 3) (4.8mg, 0.0104mmol), the 30mL The flask was placed in a two-necked eggplant flask and purged with argon. Dichloromethane (1.5 mL) was added thereto, and further pyridine (0.02 mL, 0.24 mmol) was added. After stirring at 0 ° C. for 5 minutes, benzoyl chloride (0.04 mL, 0.26 mmol) was added dropwise. After stirring at room temperature for 12 hours, the reaction was quenched with 2M hydrochloric acid. The mixture was extracted with ethyl acetate, and the collected organic layer was washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The filtrate filtered through a cotton plug was concentrated with an evaporator to obtain a crude product.

収率 ：４２％（１２．９ｍｇ）
Ｒｆ値：０．８２（ヘキサン：酢酸エチル＝１：１）
形状 ：無色オイル状 The obtained crude product was purified by thin layer chromatography (hexane: ethyl acetate = 9: 1), and further purified by thin layer chromatography (hexane: ethyl acetate = 1: 1). was obtained O- benzoyl 2-O- benzyl-3-mono-12-benzoyloxy -cis-9-Okutade cell noil glycerol. The diastereomer ratio (% de) of this was 60%. From this, it was found that the diastereomer ratio (% de) of the compound obtained in Enzyme Reaction Example 4 (the compound of Entry 1 in Table 3) was 60% as shown in Table 3.

Yield: 42% (12.9 mg)
Rf value: 0.82 (hexane: ethyl acetate = 1: 1)
Shape: colorless oil

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.85 (t, J = 5.3 Hz, 3H), 1.21-1.32 (m, 16H), 1.57-1.67 (m, 4H), 2.00-2.05 (m, 2H) , 2.31 (t, J = 7.4Hz, 2H), 2.42 (dd, J = 5.9, 11.9Hz, 2H), 3.97 (t, J = 5.2Hz, 1H), 4.22-4.52 (m, 4H), 4.71 ( s, 2H), 5.09-5.16 (m, 1H), 5.38-5.49 (m, 2H), 7.26-7.34 (m, 5H), 7.37-7.47 (m, 4H), 7.52-7.60 (m, 2H), 8.00-8.05 (m, 4H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 173.5, 166.2, 166.2, 137.7, 133.1, 132.7, 132.7, 130.8, 129.7, 129.5, 128.4, 128.4, 128.2, 127.9, 127.8, 124.1, 74.6, 74.4, 72.1, 63.7, 63.0, 34.1, 33.7, 32.0, 31.7, 29.5, 29.2, 29.1, 29.1, 29.1, 27.3, 25.3, 24.9, 22.6, 14.0

IR (neat): 2928,2857,2361,1720,1602,1453,1314,1273,1174,1111,1069,1027,712 cm ^-1

  In Enzyme Reaction Example 4, in place of Entry 1 in Table 3, the conditions shown in Entry 2 to 3 in Table 3 and Entry 1 to 5 in Table 4 were the same as in Enzyme Reaction Example 4 except that Entry 2 to 3 in Table 3 were used. , Entry 1 to 5 in Table 4 were synthesized. Further, in the same manner as in Measurement Example 4, benzoylation and diastereomer ratio (% de) were measured to determine the diastereomeric ratios of the compounds shown in Entry 2 to 3 in Table 3 and Entry 1 to 5 in Table 4 ( % De). The results are summarized in Tables 3 and 4.

3. Liquid crystal synthesis synthesis example 1
<Synthesis of 1-O-4-hexyloxy-4-carboxy -2-O-methoxymethyl-3-mono-12-hydroxy -cis-9-Okutade cell noil glycerol>
Two-necked eggplant flask 30mL, Entry5 of the compounds of Table 2 obtained in the enzyme reaction Example 3 1-mono-12-hydroxy -cis-9-Okutade cell noil -2-O-methoxymethyl-glycerol (55.5 mg, 0.133 mmol) was added, and 4-dimethylaminopyridine (37.4 mg, 0.31 mmol) was weighed and added to perform argon replacement. Dichloromethane (1.0 mL) was added to 4- (4-hexyloxyphenyl) benzoic acid (59.6 mg, 0.20 mmol), added dropwise to the reaction system, and washed with dichloromethane (1.0 mL). Was added twice.

  After stirring at 0 ° C. for 5 minutes, dichloromethane (1.0 mL) was added to 1,3-dicyclohexylcarbodiimide (68.7 mg, 0.33 mmol), and the mixture was added dropwise to the reaction system, and washed again with dichloromethane (1.0 mL). The washing solution was added to the reaction system and stirred for 48 hours, followed by Celite filtration using ethyl acetate, and the filtrate was washed with 0.5 M aqueous hydrochloric acid and dried over anhydrous sodium sulfate. The filtrate filtered with a cotton plug was concentrated by an evaporator to obtain a crude product.

収率 ：３３％（３０．５ｍｇ）
Ｒｆ値：０．５（ヘキサン：酢酸エチル＝３：１）
形状 ：無色オイル状
［α］_D ²⁶＝＋０．９１（ｃ０．２９，ＣＨＣｌ₃） The obtained crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 6: 1), and the following 1-O-4-hexyloxybiphenyl-4-carboxy-2-O-methoxymethyl-3- to obtain a mono-12-hydroxy -cis-9-Okutade cell noil glycerol.

Yield: 33% (30.5 mg)
Rf value: 0.5 (hexane: ethyl acetate = 3: 1)
Shape: colorless oil [α] _D ²⁶ = + 0.91 (c0.29, CHCl ₃ )

¹ H NMR (270 MHz, CDCl ₃ ): δ 0.80-0.90 (m, 6H), 1.20-1.40 (m, 22H), 1.40-1.53 (m, 4H), 1.52-1.72 (m, 3H), 1.76- 1.86 (m, 2H), 1.98-2.12 (m, 2H), 2.18-2.23 (m, 2H), 2.35 (t, J = 7.4
Hz, 2H), 3.41 (s, 3H), 3.55-3.68 (m, 1H), 4.01 (t, J = 6.6Hz, 2H), 4.11-4.58 (m, 5H), 4.77 (s, 2H), 5.37 -5.44 (m, 1H), 5.50-5.59 (m, 1H), 6.95-7.00 (m, 2H), 7.48-7.64 (m, 4H), 8.04-8.09 (m, 2H)

¹³ C NMR (67.8 MHz, CDCl ₃ ): δ 14.0, 14.1, 22.6, 24.8, 25.7, 27.4, 29.0, 29.1, 29.2, 29.3, 29.5, 31.6, 31.8, 34.1, 35.4, 36.8, 55.663.4, 63.9,71.5,72.7,77.2,96.0,114.9,125.2,126.3,126.5,127.7,128.0,128.3,130.2,132.0,133.3,145.6,159.5,166.2,173.5

IR (neat): 2929,2857,1721,1605,1497,1466,1274,1186,1111,1035,829,757cm ^-1

Synthesis example 2
In Synthesis Example 1 above, instead of the compound of Entry 5 in Table 2 obtained in Enzyme Reaction Example 3, the compounds of Entry 1 to 4 in Table 1 obtained in Enzyme Reaction Example 1 and the table obtained in Enzyme Reaction Example 2 2, the compounds of Entry 1 to 4 of Table 2, the compounds of Entry 6 of Table 2 obtained in Enzyme Reaction Example 3, the compounds of Entry 1 to 3 of Table 3 obtained in Enzyme Reaction Example 4 and the compounds of Entry 1 to 5 of Table 4 were respectively obtained. 4- (4-Hexyloxyphenyl) benzoic acid was reacted in the same manner as in Synthesis Example 1 except that it was used to obtain compounds corresponding to the respective compounds.

Evaluation Example <Measurement of DSC Curve>
Using a thermal analysis system, 1-O-4-hexyloxybiphenyl-4-carboxy-2-O-methoxymethyl-3-mono-12-hydroxy-cis-9- obtained in Synthesis Example 1 as a sample was used as a sample. the Okutade cell noil glycerol was measured. The sample starts at room temperature and is heated at a temperature from −100 ° C. to 200 ° C. by changing 5 ° C. per minute in the order of room temperature, 50 ° C., −100 ° C., 200 ° C., −100 ° C., and room temperature. And the exotherm of heat when the temperature was lowered from 200 ° C. to −100 ° C. were measured. In addition, at 200 degreeC and -100 degreeC, the temperature was maintained for 5 minutes, respectively. The results are shown in FIG.

  Looking at the DSC curve in FIG. 1 in the temperature rising direction, four peaks a, b, c, and d, which are heat absorption, can be confirmed. This indicates that the liquid phase is changed from the solid phase through the three liquid crystal phases as the temperature rises. When a sample is subjected to thermal analysis, the phase of the substance appears as a peak when it undergoes a phase transition to another phase. That is, in the DSC curve in the temperature rising direction of FIG. 1, the peak a is a peak at the time of phase transition from the solid phase to the liquid crystal phase, and the peak of d represents the phase transition from the liquid crystal phase to the liquid phase. In other words, a liquid crystal phase could be confirmed between about −20 ° C. and about 75 ° C.

  Similarly, two peaks e and f were confirmed in the temperature decreasing direction. That is, a phase transition via one liquid crystal phase was observed, and a liquid crystal phase could be confirmed between about −20 ° C. and about 75 ° C.

  From the above, it was found that the compound represented by the general formula (1) may have a liquid crystal phase.

  The liquid crystal compound according to the present invention is environmentally friendly, and a novel ferroelectric liquid crystal compound in which an asymmetric carbon is introduced using an enzyme reaction excellent in production efficiency is widely used for displays and the like. .

2 is an example of a DSC curve of the compound synthesized in Synthesis Example 1.

Claims (2)

A ferroelectric liquid crystal material containing an asymmetric carbon atom and exhibiting optical activity, wherein the asymmetric carbon atom is introduced using an enzyme reaction, and is represented by the following general formula (1) A ferroelectric liquid crystal material characterized by having a chemical structure.

[In general formula (1),
X may have a substituent selected from the group consisting of a methyl group, an ethyl group, a hydroxyl group, a methoxyl group, an ethoxyl group, a halogen group, a methoxymethyl group and a methoxyethoxymethyl group, a benzene ring, a naphthalene ring, Anthracene ring, phenanthrene ring, pyrene ring, pyrrole ring, imidazole ring, pyrazole ring, pyridine ring, pyrimidine ring, purine ring, quinoline ring, carbazole ring, furan ring, thiophene ring, oxazole ring or thiazole ring,
R ¹ represents an alkyl group having 1 to 24 carbon atoms or an alkenyl group having 2 to 24 carbon atoms, which may have a substituent selected from the group consisting of a hydroxyl group, an alkyloxy group, an aryloxy group, and an ester group. Show
R ² is a C 1-6 alkyl group which may have a substituent selected from the group consisting of a methoxyl group, an ethoxyl group, a benzyloxy group, a vinyl group, a phenyl group and a methoxyethoxyl group, or —COR ′. (R ′ represents a lower alkyl group or a halogen group which may have a substituent as a substituent, an alkyl group having 1 to 6 carbon atoms or a phenyl group),
R ³ represents an alkyl group having 1 to 13 carbon atoms which may have a substituent. ] In the general formula (1), R ¹ is — (CH ₂ ) ₇ CH═CHCH ₂ CH (OH) (CH ₂ ) ₅ CH ₃ or — (CH ₂ ) ₁₀ CH (OH) (CH ₂ ). _The ferroelectric liquid crystal material according to claim 1, wherein the ferroelectric liquid crystal material is ₅ CH ₃ .

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