JPH03112939A - Cyclopentane - Google Patents

Abstract

NEW MATERIAL:A cyclopentane of formula I [R1 is methoxyethoxymethoxy; R2 is tetrahydropyranyl, H or -CO2CH2CX3 (X is halogen); R3 is OH, cyano or -CO2R4 (R4 is lower alkyl)]. EXAMPLE:[1R',2S',3S'] 1-methoxyethoxymethoxy-2-[5'-tetrahydropyranyloxy-3(2)- pentenyl]-3-hydroxymethylcyclopentane. USE:A synthetic intermediate for 5'-hydroxyepijasmonic acid known as an inducer for potato tuber formation. PREPARATION:For example, [1S',2R',5S']-2-methoxyethoxymethoxy-8-ethoxy-7- oxabicyclo[4,3,0]nonane of formula II is hydrolyzed with acetic acid, and put to Wittig reaction with 3-tetrahydropyranoxypropylidene triphenylphosphine in an organic solvent to obtain one of the compounds of the formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention provides a method for producing 5-hydroxyevijasmonic acid, which is useful as an intermediate for the synthesis of 5-hydroxyevijasmonic acid, which is known as a potato tuber formation inducer, and which has not been described in the prior literature. The present invention relates to novel cyclopentanes represented by the following formula (1) and methods for producing them.

More specifically, the present invention relates to the following formula (1), which is useful as a synthetic intermediate for 5-hydroxyevijasmonic acid represented by the following formula (A), which is useful as a potato tuber forming substance, where R+ is methoxyethoxy. Represents a methoxy group (-0MEM), R2 represents a tetrahydropyranyl group (THP), a hydrogen atom or a group -CO2CH2CX3 (where X represents a halogen atom), R3 represents a hydroxyl group (-OH), a cyano group ( −
CN) or a group -CO2RJ (herein, R4 represents a lower alkyl group), and a method for producing them.

(Prior Art) Until now, there has been no synthesis of 5-hydroxyevijasmonic acid, which is known as a potato tuber-forming substance represented by the above formula (A), and there has been no synthesis intermediate for the compound of the above formula (A). The compounds of the above formula (1) of the present invention are also novel compounds that have not been known until now.

(Problems to be Solved by the Invention) As described above, the present inventors have conducted intensive research on the synthesis of 5-1-hydroxyevijasmonic acid of formula (A), which has never been synthesized before. As a result, the inventors discovered that the compound represented by the above formula (1) can be used as a synthetic intermediate for the compound represented by the linear formula (A), and completed the present invention.

Therefore, an object of the present invention is to provide compounds of the above formula (1) that are useful as intermediates for the synthesis of the compounds of the above formula (A), and to provide methods for producing them.

(Means for Solving the Problems) Compounds of formula (1) of the present invention useful as synthetic intermediates for the compound of formula (A) above are represented by the following formula (2), for example, [IS'', 2R' , 5S'co2-methoxyethoxymethoxy-8-ethoxy-7-oxabicyclo[4,3,01 is synthesized using nonane as a starting material.

The compound of formula (2) can be easily synthesized, for example, by the method described in Japanese Patent Application No. 63-261656 proposed by the applicant.

To synthesize compounds included in the compound of formula (1) of the present invention, first, the compound of formula (2) is hydrolyzed with acetic acid,
Then, Witt
ig) React to produce [IR'2S'3S' ]-] represented by the following formula (3) included in formula (1)
1-Methoxyethoxymethoxy-2[5-tetrahydropyranyloxy-3(Z)-pentenyl-3-hydroxymethylcyclopentane is formed. Next, the compound of linear formula (3) is reacted with mesyl chloride to form linear formula (
The mesylate of 3) is formed, and then this mesylate is reacted with sodium cyanide or potassium cyanide to form a mesylate [IR'', 2S'', 3R°co1- Methoxyethoxymethoxy-2-[5-tetrahydropyranyloxy-3(Z)-pentenyl]-3-cyanomethylcyclopentane is produced.

Next, the compound of linear formula (4) is hydrolyzed with an acid catalyst,
[IR
', 2S', 3R']-]1-methoxyethoxymethoxy-2[5-hydroxy-3(Z)-pentenyl-3-cyanomethylcyclopentane. Next, the compound of the linear formula (5) is hydrolyzed with an alkali to give a carboxylic acid, and this carboxylic acid is reacted with a lower alcohol in the presence of cyazomethane or an acid catalyst.
) represented by the following formula (6)
)-pentenyl]-3-methoxylponylmethylpentane, and then the compound of linear formula (6) was converted to chloride 1!2. 2.
2-) By reacting with dichloroethyl, [IR", 2S", 3 represented by the following formula (7) included in formula (1)
R”]-]1-methoxyethoxymethoxy2[5-
Monotrichloroethoxycarbonyloxy-3(Z)-pentenyl-3-methoxycarbonylmethylcyclopentane is formed.

The compound of formula (7), which can be synthesized as described above, can be synthesized by, for example, a MEM removal step, an oxidation step, and a removal of -C
The compound of the above formula (A) can be derived via O2CH2CX3.

When the method for synthesizing the cyclohexanes included in the above formula (1) of the present invention is shown in a reaction process diagram, it can be expressed, for example, as follows.

(Margin below) (2) (5) (4) (6) (7) (A) The present invention will be explained in detail below according to the above steps.

In the above process diagram, in order to synthesize the compound of formula (3) from the compound of formula (2), the compound of formula (2) is first hydrolyzed with an acid such as acetic acid to open the ring. There is no particular restriction on the amount of acid used in this case, and it is usually about 1 to 10 times the weight of the compound of formula (2). This acid such as acetic acid is generally used in the form of an aqueous solution, and its concentration is often in the range of about 40 to about 90% by weight. Further, it is sufficient to carry out this reaction at a temperature of about 20° C. to about 60° C. for about 1 to 5 hours. After the reaction is completed, the crude product is obtained by neutralizing with an alkali, extracting with a solvent such as methylene chloride, and concentrating according to a conventional method. This crude product was not purified by a known method [J, Org, Ch.
A Wittig reaction is carried out with 3-tetrahydropyranoxypropylidene triphenylphosphorane obtained in [Em., 44.3760 (1979)]. This reaction is usually carried out in an organic solvent such as tetrahydrofuran at a temperature ranging from water cooling to room temperature. The reaction time is often in the range of about 1 to 10 hours at room temperature.

The above WitTig reagent is used in an amount of about 1 to 5 moles per mole of the crude product. Also, the amount of organic solvent used depends on the organic solvent used, but -
For boat fishing, the amount may be about 1 to 10% by weight based on the above crude product.

After completion of the reaction, the reaction solution is poured into, for example, a saturated aqueous ammonium chloride solution, extracted with a solvent such as ether, concentrated to dryness, and purified by means such as column chromatography to easily obtain the compound of formula (3). Obtainable.

In order to obtain the compound of formula (4) from formula (3) thus obtained, the compound of formula (3) is first dissolved in an organic solvent and reacted with mesyl chloride to form the compound of formula (3). Convert to mesylate. This reaction is usually carried out under water cooling, for example, at a temperature of about 10° C. to about 20° C. for about 1 to 10 hours.

The amount of mesyl chloride used in this reaction is determined by the formula (
For example, it is sufficient to use about 1 to 2 moles per mole of the compound 3). Examples of the organic solvent include basic ones such as pyridine and triethylamine, and the amount used is, for example, about 2 to 10 times the weight of the compound of formula (3). be done. After the reaction is completed, the reaction solution is washed with an aqueous alkaline solution, concentrated and dried to obtain a crude mesylate compound of formula (3).Next, this crude mesylate compound is mixed with sodium cyanide, potassium cyanide, The compound of formula (4) can be synthesized by reacting with a cyanide such as cyanide steel. In this case, it is preferable to carry out the reaction in the presence of a quaternary ammonium salt such as tetrabutylammonium iodide in the reaction system, and preferably in an inert gas atmosphere such as argon. The reaction is carried out, for example, at about 50°
The process is carried out at a temperature of ~1°C for approximately 10 to 30 hours. The amount of cyanide used above is
The appropriate amount is, for example, about 2 to 10 mol per mol of the mesylate compound of formula (3).

Further, as the organic solvent used in this reaction, there are solvents such as dimethyl sulfoxide, dimethylformamide, methanol, ethanol, etc., and the amount used can be selected appropriately, but for example, the mesylate compound of formula (3) A range of about 5 to 20 times the weight is often adopted.

After the reaction is complete, water is added to the reaction solution, the product is extracted with a solvent such as methylene chloride, the organic layer is washed with water, dried and concentrated, and then prepared using a method such as column chromatography to obtain the formula Compound (4) can be synthesized.

Next, from the compound of formula (4) obtained above, formula (1)
The compound of formula (5) included in the compounds of formula (4) can be easily obtained by reacting the compound of formula (4) with an acid in an organic solvent to remove the tetrahydropyranyl group.

This reaction is carried out at a temperature around room temperature, for example, for about 10 to 30 hours. Any organic solvent can be used in the reaction without any particular problem, but methanol, ethanol, propatool, etc. are often used for boat fishing. Examples of acids used in this reaction include pyridinium p-)luenesulfonate and acetic acid. The amount of these acids to be used can be determined, for example, by the formula (
It is used in an amount of about 5 to 50% based on the compound of 4). Further, the amount of the organic solvent to be used is, for example, approximately 5 to 50 times the weight of the compound of formula (4). After the reaction is completed, the product is neutralized with an alkali, concentrated, extracted with a solvent such as methylene chloride, washed with water, dried and concentrated, and purified by means such as column chromatography to obtain the formula (5). The compound is obtained.

From the compound of formula (5) synthesized as described above, formula (
To synthesize the compound of formula (6) included in the compounds of 1), for example, the compound of formula (5) is preferably treated with an alkali in a solvent to form a carboxylic acid derivative, and then the compound is treated with sulfuric acid or hydrochloric acid. The compound of formula (6) can be easily synthesized by reacting with an acid such as to synthesize a carboxylic acid, and reacting this with a lower alcohol in the presence of diazomethane or an acid catalyst.

The above-mentioned hydrolysis reaction with an alkal is usually carried out under heating, for example, in a range of about 20° to 100°C, and for a reaction time of about 10 to 30 hours, for example. Examples of the alkali used here include potassium hydroxide, sodium hydroxide, etc., and the amount used is, for example, about 1 to 5 moles relative to the compound of formula (5). After hydrolysis, a carboxylic acid can be obtained by treatment with the above-mentioned acid according to a conventional method. Although the obtained acid may be purified, it can usually be used as a raw material for the next esterification reaction without being purified. The esterification reaction may be a reaction with a lower alcohol or a reaction with diazomethane, but the reaction with a lower alcohol will be described below. This reaction is about 10
This is carried out at a temperature of about 50"C for about 1 to 5 hours. Examples of acid catalysts used include phosphoric acid, sulfuric acid, para-toluenesulfonic acid, etc., and the amount used is, for example, Based on the above-mentioned carboxylic acid, a range of about 1 to 5% is appropriate.As for the lower alcohol, for example, methyl, ethyl, 1-propyl, furovir, l
Lower alkyl alcohols such as -butyl, n-butyl, etc. are used. In addition, the amount of these alcohols to be used is, for example, the above-mentioned carvone! For 1 mole,
For example, after the reaction is completed, the product is extracted with an organic solvent such as ether, the solvent layer is neutralized with an appropriate alkali, and then subjected to treatments such as drying and acondensation. The compound of formula (6) is obtained by purification by means such as column chromatography.

Next, the compound of formula (6) obtained as above was mixed with chloroformic acid 2. 2. 2-) By reacting with fuchloroethyl, the compound of formula (7) included in the compound of formula (1) can be easily synthesized.

This reaction is usually carried out in an organic solvent at, for example, room temperature for about 10 to 30 hours.

Chloroformic acid2. 2. The amount of 2-)lichloroethyl to be used is preferably in the range of about 1 to 2 mol, for example, per 1 mol of the compound of formula (6). Further, as the base, bases such as pyridine, triethylamine, and diisopropylethylamine are used.

The amount of this base to be used is the same as that of chloroformic acid 2. 2. 2-
For example, it is used in an amount of about 2 to 8 mol per mol of trichloroethyl. In addition, the organic solvent used in this reaction is often, for example, methylene chloride or chloroform, and there are no particular restrictions on the amount used, and the reaction can be appropriately selected. On the other hand, it can be used in a wide range, for example, about 1 to 20 times the weight.

After the reaction is completed, the mixture is treated with an alkaline aqueous solution such as sodium hydrogen carbonate for about 30 minutes. Thereafter, the product is extracted with an organic solvent such as methylene chloride, and the solvent layer is washed with an aqueous alkaline solution, dried, concentrated, and purified by means such as column chromatography to obtain the formula (7).
) can be easily obtained.

Hereinafter, the manner in which the present invention is implemented will be explained in more detail with reference to Examples.

(Example) Example 1 [IR', 2S'', 3S'1-1-Methoxyethoxymethoxy-2-[5--tetrahydropyranyloxy-3
Synthesis of (Z)-pentenyl]-3-hydroxymethylcyclopentane c formula (3)] 12.04 g of compound of formula (2)
(0,044 mol), 72 g of acetic acid, and 24 g of water are stirred at 40° to 50° C. for 3.5 hours. The reaction solution was poured into an aqueous solution containing 72 g of sodium hydrogen carbonate, and extracted with methylene chloride. The organic layer is washed with aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and concentrated. 42.48 g of crude 3-tetrahydrobyranoxybrobyltriphenylphosphonium bromide, 300 ml of dry tetrahydrofuran, 20.4 ml of 1°6Nn-BuLj
The reaction mixture α was added to the Wittig reagent prepared above for 30 minutes under water cooling and stirred overnight.The reaction mixture α was poured into a saturated aqueous ammonium chloride solution and extracted with ether. The ether layer is washed with an aqueous soda ash solution, dried over anhydrous magnesium sulfate, and concentrated.

The residue was purified by silica gel column chromatography, and the formula (
3) 7.4 g (yield: 676%) of the compound was obtained.

Rf value; 0.42 (n-hexane: ethyl acetate = 1:1
) IR (cm''); 3388.3080,2944°1437, 1352,1201.1120,103
3.905,870,814 Example 2 [IR", 2S", 3R" 1-1-methoxyethoxymethoxy-2-[5-tetrahydropyranyloxy-3
Synthesis of (Z)-pentenyl-3-cyanomethylcyclopentane [formula (4)] 7.4 g (0.02 mol) of the compound of formula (3) and 7.4 g of triethylamine are dissolved in 120 ml of methylene chloride.

A mixture of 4.56 g of mesyl chloride and 20 ml of methylene chloride was added dropwise at 5'' to 7° C. under water cooling over 30 minutes, and the mixture was further stirred at the same temperature for 2 hours.

A saturated aqueous sodium hydrogen carbonate solution is added to the reaction mixture, and after stirring for 30 minutes, the mixture is separated and further washed with a saturated aqueous sodium hydrogen carbonate solution. Next, it is dried over anhydrous magnesium sulfate and concentrated. 100 ml of crude dimethyl sulfoxide, 9.8 g of sodium cyanide.

Add 1 g of tetrabutylammonium iodide and heat at 70° C. for 48 hours under argon gas. After cooling, water is added and extracted with methylene chloride, and the organic layer is washed with water, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified using silica gel column chromatography to obtain the compound of formula (4) as 5
．． 46g was obtained. Yield: 71.6%.

Rf: 0. 62 (n-hexane:ethyl acetate=
1: I IR (cm-'); 2944, 2B73.2248°1456.1354, 1201, 1158, 1122.
1079.1036 Example 3 [IR″, 2S′, 3R′-1-methoxyethoxymethoxy-2-[5-hydroxy-3(Z)-pentenyl]-3-cyanomethylcyclopentane [Formula (5)]
5.46 g (14.34 mmol) of the compound of synthetic formula (4) was dissolved in 120 ml of methanol, 0.54 g of pyridinium p-)luenesulfonate was added, and the mixture was stirred at room temperature for 20 hours. Add a small amount of sodium carbonate powder to the reaction solution and concentrate. Add water, extract with methylene chloride, wash with water, dry over anhydrous magnesium sulfate, and concentrate. The residue was purified using silica gel chromatography to obtain a compound of formula (5) with 3.5
I got 4g. Yield: 88.5% Rf: 0.2B (n-hexane:ethyl acetate=]
: 1) TR (cm-'); 344B, 2938.288
2゜2250, 1170. 1108. 1046.
926 849 Example 4 [IR", 2S', 3R" two-1-methoxyethoxymethoxy-2-[5-hydroxy-3(z)
Synthesis of -bentenyl-3-methoxycarbonylmethylcyclopentane 0 Formula (6) Compound 0.7 g (2.5 mmol), methanol 14 ml Water 2.8 ml, Sodium hydroxide 1.4
The mixture of g is heated at 60° C. for 3 days. The reaction solution is poured into water and extracted with ether to recover the unreacted compound of formula (5). Subsequently, dilute sulfuric acid is added to make the mixture acidic, and the mixture is extracted with methylene chloride. The organic layer is washed with water and dried over anhydrous '6Rrli magnesium to obtain 44 g of crude product. This is dissolved in a small amount of ether and added to an ether solution of diazomethane for methyl esterification. Ether was removed to obtain 0.54 g of the compound of formula (6). Yield: 89% Rf value: 0.31 (n-hexane:acetic acid = 1:1) IR
(cm”); 3454,2940.1738°14
37, 1201. 11?0. 1106,1044
．． 934,849 Example 5 [IR', 2S'', 3R°]-1-Methoxyethoxymethoxy-2-[5-trichloroethoxycarbonyloxy-3(Z)-pentenyl]-3-methoxylponylmethylcyclo Bentane [Formula 4 %] 0.74 g of 2.2.2-)lichloroethyl chloroformate was added to a mixture of 0.54 g (1.74 mol) of the compound of formula (6), 20 ml of methylene chloride, and 4 ml of lysine. Add dropwise. Stir overnight at room temperature, add aqueous sodium hydrogen carbonate solution to the reaction mixture, and stir for 30 minutes.

Extracted with methylene chloride, washed the organic layer with an aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and extracted with il!
I'm going to iki. The residue was purified using silica gel column chromatography to obtain 0.76 g of the compound of formula (7). Yield: 89.6% Rf value: 0.70 (n-hexane: ethyl acetate = 1;
I IR (cm-'); 2940, 1760, 1735
゜1437, 1396. 1373. 1245,1
170.1137.1106.1045 <Effects of the Invention> According to the present invention, 5 which is a potato tuber formation inducer
--The novel formula (
1) cyclopentanes and methods for producing them can be provided.

Claims (1)

[Claims] 1. The following formula (1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (1) In the formula, R_1 is a methoxyethoxymethoxy group (-OME
M), R_2 is a tetrahydropyranyl group (THP
), represents a hydrogen atom or a group -C O_2CH_2CX_3 (where X represents a halogen atom), and R_3 represents a hydroxyl group (-OH), a cyano group (-
CN) or a group -CO_2R_4 (where R_4 represents a lower alkyl group).