JPS6328052B2 - - Google Patents
Info
- Publication number
- JPS6328052B2 JPS6328052B2 JP5072380A JP5072380A JPS6328052B2 JP S6328052 B2 JPS6328052 B2 JP S6328052B2 JP 5072380 A JP5072380 A JP 5072380A JP 5072380 A JP5072380 A JP 5072380A JP S6328052 B2 JPS6328052 B2 JP S6328052B2
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- alcohol
- optical
- formula
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 42
- 230000003287 optical effect Effects 0.000 claims description 27
- -1 alcohol compound Chemical class 0.000 claims description 25
- 235000019441 ethanol Nutrition 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- 244000063299 Bacillus subtilis Species 0.000 claims description 6
- 235000014469 Bacillus subtilis Nutrition 0.000 claims description 6
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000003797 solvolysis reaction Methods 0.000 claims 1
- 238000000034 method Methods 0.000 description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- QMSYFNBRKYPTKN-BQYQJAHWSA-N (e)-4-methyloct-4-en-1,7-diyn-3-ol Chemical compound C#CC(O)C(/C)=C/CC#C QMSYFNBRKYPTKN-BQYQJAHWSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- JJYKJUXBWFATTE-UHFFFAOYSA-N mosher's acid Chemical compound COC(C(O)=O)(C(F)(F)F)C1=CC=CC=C1 JJYKJUXBWFATTE-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明はジエチルエーテル中で（−）の旋光性
を示す光学活性な式（）
で示されるアルコール化合物及びその製造法に関
するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention provides an optically active formula () exhibiting (-) optical rotation in diethyl ether. The present invention relates to an alcohol compound represented by and a method for producing the same.
即ち、本発明は式（）
で示されるアセテート化合物にBacillus subtilis
var niger（IFO3108）を作用させ、その一方の光
学異性体を選択的に加水分解させ、対応する光学
活性なアルコール化合物に導いた後、これを分離
除去することにより前記式（）で示されるもう
一方の光学異性体を得、この光学活性なアセテー
ト化合物をメチルアルコールまたはエチルアルコ
ール中で、触媒量の塩基の存在下に加溶媒分解す
ることによる前記式（）で示されるジエチルエ
ーテル中で（−）の旋光性を示す光学活性なアル
コール化合物の製造方法を提供するものである。 That is, the present invention is based on the formula () The acetate compound shown by Bacillus subtilis
var niger (IFO3108) to selectively hydrolyze one of the optical isomers, leading to the corresponding optically active alcohol compound, which is then separated and removed to form the other optical isomer represented by the above formula (). One of the optical isomers was obtained, and the optically active acetate compound was solvolyzed in methyl alcohol or ethyl alcohol in the presence of a catalytic amount of base to give (- ) provides a method for producing an optically active alcohol compound exhibiting optical rotation.
式（）
で示されるカルボン酸エステルは種々の衛生害虫
に対し極めて強いノツクダウン効力及び致死効力
を有している（Jap.J.Sanit.Zool.、vol.29、No.３、
219〜224、1978）。 formula() The carboxylic acid ester shown by has extremely strong knockdown and lethal effects against various sanitary pests (Jap.J.Sanit.Zool., vol.29, No.3,
219-224, 1978).
前記式（）で示されるアルコール化合物は、
該カルボン酸エステルのアルコール成分であり、
中間体として極めて重要である。また、該アルコ
ール化合物には不斉炭素原子があり２種類の光学
異性体が存在するが、いまだに光学活性な前記式
（）で示されるアルココール化合物は得られて
いない。その光学異性体の中で、ジエチルエーテ
ル中で（−）の旋光性を示す（Ｅ）−３−ヒドロ
キシ−４−メチル−オクタ−４−エン−１，７−
ジインの（±）−３−（２，２−ジクロルビニル）
−２，２−ジメチルシクロプロパンカルボン酸と
のエステルは、ラセミ体の（Ｅ）−３−ヒドロキ
シ−４−メチル−オクタ−４−エン−１，７−ジ
インの該カルボン酸とのエステルに比し、約２倍
の強い殺虫効力を有しているにもかかわらず、こ
のアルコール化合物が塩基に対して不安定なアセ
チレン鎖を有しているため、通常の光学分割の手
法では高収率、高純度にその光学活性体を得るこ
とはできなかつた。 The alcohol compound represented by the above formula () is
an alcohol component of the carboxylic acid ester,
It is extremely important as an intermediate. Further, although the alcohol compound has an asymmetric carbon atom and exists in two types of optical isomers, an optically active alcohol compound represented by the above formula () has not yet been obtained. Among its optical isomers, (E)-3-hydroxy-4-methyl-oct-4-ene-1,7- exhibits (-) optical rotation in diethyl ether.
Diyne (±)-3-(2,2-dichlorovinyl)
The ester with -2,2-dimethylcyclopropanecarboxylic acid is compared to the ester of racemic (E)-3-hydroxy-4-methyl-oct-4-ene-1,7-diyne with said carboxylic acid. Although it has about twice as strong insecticidal efficacy, this alcohol compound has an acetylene chain that is unstable to bases, so it cannot be used in high yield with ordinary optical resolution methods. It was not possible to obtain the optically active substance with high purity.
本発明者らは、鋭意研究を重ねた結果、
Bacillus subtilis var niger（IFO3108）を用いる
ことにより、光学純度の高い前記式（）で示さ
れる（Ｅ）−３−アセトキシ−４−メチル−オク
タ−４−エン−１，７−ジインが得られることを
見出し、さらにここで得られたアセテート化合物
をメチルアルコールまたはエチルアルコール中
で、触媒量の塩基の存在下に加溶媒分解すること
により、ジエチルエーテル中で（−）の旋光性を
示す光学純度の高い（Ｅ）−３−ヒドロキシ−４
−メチル−オクタ−４−エン−１，７−ジインを
合成することに成功した。 As a result of extensive research, the present inventors found that
By using Bacillus subtilis var niger (IFO3108), (E)-3-acetoxy-4-methyl-oct-4-ene-1,7-diyne represented by the above formula () with high optical purity can be obtained. Furthermore, by solvolyzing the acetate compound obtained here in methyl alcohol or ethyl alcohol in the presence of a catalytic amount of base, a compound of optical purity exhibiting (-) optical rotation in diethyl ether was obtained. High (E)-3-hydroxy-4
-Methyl-oct-4-ene-1,7-diyne was successfully synthesized.
Bacillus subtilis var niger（IFO3108）を用い
てピレスロイドのアルコール成分の光学分割を試
みた例としては、折谷らのアレスロニルアセテー
トの分割が知られている（Agr.Biol.Chem.、39、
89〜96（1975））が、これにより得られる生物活性
上有利な（＋）の旋光性を示すアレスロニルアセ
テートの光学純度は約50％であり、光学活性体の
取得法としては実用的とは言い難い。 An example of an attempt to optically resolve the alcohol component of a pyrethroid using Bacillus subtilis var niger (IFO3108) is the resolution of allethronyl acetate by Oriya et al. (Agr. Biol. Chem., 39 ,
89-96 (1975)), the optical purity of allethronyl acetate that exhibits (+) optical rotation, which is advantageous in terms of biological activity, is approximately 50%, making it a practical method for obtaining optically active substances. It's hard to say.
本発明方法によれば意外にも、生理活性上極め
て有利な、ジエチルエーテル中で（−）の旋光性
を示す前記一般式（）で示される光学活性な
（Ｅ）−３−ヒドロキシ−４−メチル−オクタ−４
−エン−１，７−ジインを極めて高い光学純度
で、しかも比較的高収率で得ることができ、未だ
有効な光学分割法が見出されていない現状を考え
るとその意義は極めて大きいものがある。 According to the method of the present invention, optically active (E)-3-hydroxy-4- represented by the general formula () which exhibits (-) optical rotation in diethyl ether, which is extremely advantageous in terms of physiological activity, has been surprisingly obtained. Methyl-octa-4
-Ene-1,7-diyne can be obtained with extremely high optical purity and in a relatively high yield, and this is extremely significant considering that no effective optical resolution method has yet been found. be.
本発明を行なうに際しては、Bacillus subtilis
var niger（IFO3108）の培養液に前記式（）で
示されるアセテート化合物を加えて培養を継続す
る方法が最も良く行なわれる。この時、培養温度
は菌の増殖が可能であれば特に制限はないが、通
常25〜30℃で行なうのが好ましく、培養日数は通
常半日〜７日間が適当である。また基質濃度は培
養物の0.1〜10％程度である。 In carrying out the present invention, Bacillus subtilis
The most common method is to add an acetate compound represented by the formula () to a culture solution of var niger (IFO3108) and continue culturing. At this time, the culture temperature is not particularly limited as long as the bacteria can proliferate, but it is usually preferably carried out at 25 to 30°C, and the appropriate number of culture days is usually half a day to 7 days. Moreover, the substrate concentration is about 0.1 to 10% of the culture.
得られた前記式（）で示される光学活性なア
セテート化合物を加溶媒分解する際の溶媒として
はメチルアルコール、エチルアルコール、ｎ−プ
ロピルアルコールを挙げることができるが、好ま
しくはメチルアルコールまたはエチルアルコール
が用いられる。この時、反応温度は０℃〜35℃の
範囲、より好ましくは20℃〜30℃の範囲である。
また塩基の種類としては炭酸カリウム、炭酸ナト
リウム等を挙げることができ、塩基の量は該アセ
テート化合物に対し、１／200〜１／10モルの範
囲で行なうことができる。 Examples of the solvent for solvolyzing the obtained optically active acetate compound represented by the above formula () include methyl alcohol, ethyl alcohol, and n-propyl alcohol, but preferably methyl alcohol or ethyl alcohol is used. used. At this time, the reaction temperature is in the range of 0°C to 35°C, more preferably in the range of 20°C to 30°C.
Examples of the base include potassium carbonate and sodium carbonate, and the amount of the base can be in the range of 1/200 to 1/10 mole based on the acetate compound.
以下に実施例をもつて本発明をさらに詳細に説
明する。 The present invention will be explained in more detail with reference to Examples below.
実施例
100mlブイヨン培地にBacillus subtilis var
niger（IFO3108）保存株を白金耳で接種し、30℃
で２日間振盪培養して菌を生育させる。これに
（±）−（Ｅ）−３−アセトキシ−４−メチル−オク
タ−４−エン−１，７−ジイン2.12ｇを加えて30
℃で振盪培養を続けた。４日後、加水分解生成物
であるアルコール化合物と原料のアセテート化合
物の比率が約１：１になつた（ガスクロマトグラ
フによる。）ので培養を止め、培養液をセライト
過し液をエーテル抽出した。エーテル層を食
塩水で洗浄後、無水硫酸マグネシウムで乾燥し、
エーテルを留去し残渣をシリカゲルカラムクロマ
トグラフイーにより精製して、ジエチルエーテル
中で（−）の旋光性を示す（Ｅ）−３−アセトキ
−４−メチル−オクタ−４−エン−１，７−ジイ
ン0.52ｇを得た。Example Bacillus subtilis var in 100ml broth medium
niger (IFO3108) stock stock was inoculated with a platinum loop and kept at 30°C.
Culture with shaking for 2 days to grow the bacteria. Add 2.12 g of (±)-(E)-3-acetoxy-4-methyl-oct-4-ene-1,7-diyne to this and
The shaking culture was continued at °C. After 4 days, the ratio of the alcohol compound as a hydrolyzed product to the acetate compound as a raw material became approximately 1:1 (according to gas chromatography), so the culture was stopped, the culture solution was filtered through Celite, and the solution was extracted with ether. After washing the ether layer with brine, drying with anhydrous magnesium sulfate,
The ether was distilled off and the residue was purified by silica gel column chromatography to obtain (E)-3-acetoky-4-methyl-oct-4-ene-1,7, which exhibits (-) optical rotation in diethyl ether. -0.52 g of diyne was obtained.
屈折率 1.4777（20.5℃）
旋光度 −37.4゜（ジエチルエーテル、Ｃ＝1.21）
該（Ｅ）−３−アセトキシ−４−メチル−オク
タ−４−エン−１，７−ジイン0.50ｇを10mlのメ
チルアルコールに溶解し、10mgの無水炭酸カリウ
ムを加え室温で１日間撹拌した。次いでこれを水
にあけてエーテルで２回抽出し、エーテル層を食
塩水で洗浄後、無水硫酸マグネシウムで乾燥し
た。次にエーテルを留去し、残渣をシリカゲルカ
ラムクロマトグラフイーにより精製し、ジエチル
エーテル中で（−）の旋光性を示す（Ｅ）−３−
ヒドロキシ−４−メチル−オクタ−４−エン−
１，７−ジイン0.32ｇを得た。Refractive index 1.4777 (20.5°C) Optical rotation -37.4° (diethyl ether, C = 1.21) Add 0.50 g of the (E)-3-acetoxy-4-methyl-oct-4-ene-1,7-diyne to 10 ml of methyl The mixture was dissolved in alcohol, 10 mg of anhydrous potassium carbonate was added, and the mixture was stirred at room temperature for 1 day. Next, this was poured into water and extracted twice with ether, and the ether layer was washed with brine and dried over anhydrous magnesium sulfate. Next, the ether was distilled off, and the residue was purified by silica gel column chromatography to give (E)-3-, which exhibits (-) optical rotation in diethyl ether.
Hydroxy-4-methyl-oct-4-ene-
0.32 g of 1,7-diyne was obtained.
屈折率 1.4985（19.5℃）
旋光度 −32.4゜（ジエチルエーテル、Ｃ＝0.79）
当該アルコール化合物を（−）−３，３，３−
トリフルオロ−２−メトキシ−２−フエニルプロ
ピオン酸とのエステルに導いた後、ガスクロマト
グラフイーにより分析し、その光学純度を測定し
た。その結果、光学純度は90％であつた。Refractive index 1.4985 (19.5°C) Optical rotation -32.4° (diethyl ether, C = 0.79) The alcohol compound (-) -3,3,3-
After leading to an ester with trifluoro-2-methoxy-2-phenylpropionic acid, it was analyzed by gas chromatography to measure its optical purity. As a result, the optical purity was 90%.
Claims (1)
を示す光学活性なアルコール化合物。 ２ 式（） で示されるアセテート化合物にBacillus subtilis
var nigerを作用させ、その一方の光学異性体を
選択的に加水分解させ、対応する光学活性なアル
コール化合物に導いた後、これを分離除去するこ
とにより前記式（）で示されるもう一方の光学
異性体を得、この光学活性なアセテート化合物を
メチルアルコールまたはエチルアルコール中で、
触媒量の塩基の存在下に加溶媒分解することを特
徴とする式（） で示されるジエチルエーテル中で（−）の旋光性
を示す光学活性なアルコール化合物の製造方法。[Claims] 1 Formula () An optically active alcohol compound that exhibits (-) optical rotation in diethyl ether. 2 formula () The acetate compound shown by Bacillus subtilis
var niger to selectively hydrolyze one of the optical isomers, leading to the corresponding optically active alcohol compound, which is then separated and removed to form the other optical isomer represented by the above formula (). The isomer is obtained, and this optically active acetate compound is dissolved in methyl alcohol or ethyl alcohol.
Formula () characterized by solvolysis in the presence of a catalytic amount of base A method for producing an optically active alcohol compound that exhibits (-) optical rotation in diethyl ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5072380A JPS56147733A (en) | 1980-04-16 | 1980-04-16 | Optically active alcoholic compound and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5072380A JPS56147733A (en) | 1980-04-16 | 1980-04-16 | Optically active alcoholic compound and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56147733A JPS56147733A (en) | 1981-11-16 |
| JPS6328052B2 true JPS6328052B2 (en) | 1988-06-07 |
Family
ID=12866784
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5072380A Granted JPS56147733A (en) | 1980-04-16 | 1980-04-16 | Optically active alcoholic compound and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS56147733A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01257484A (en) * | 1987-12-14 | 1989-10-13 | Idemitsu Kosan Co Ltd | Method for producing optically active secondary alcohol |
-
1980
- 1980-04-16 JP JP5072380A patent/JPS56147733A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56147733A (en) | 1981-11-16 |
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