JPH01137996A - Optical resolution of optically active alcohol - Google Patents
Optical resolution of optically active alcoholInfo
- Publication number
- JPH01137996A JPH01137996A JP29218387A JP29218387A JPH01137996A JP H01137996 A JPH01137996 A JP H01137996A JP 29218387 A JP29218387 A JP 29218387A JP 29218387 A JP29218387 A JP 29218387A JP H01137996 A JPH01137996 A JP H01137996A
- Authority
- JP
- Japan
- Prior art keywords
- alcohol
- optically active
- formula
- optical resolution
- tables
- 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.)
- Pending
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 230000003287 optical effect Effects 0.000 title claims abstract description 10
- 102000004190 Enzymes Human genes 0.000 claims abstract description 10
- 108090000790 Enzymes Proteins 0.000 claims abstract description 10
- -1 alcohol compound Chemical class 0.000 claims abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 9
- 230000002366 lipolytic effect Effects 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 abstract description 11
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 11
- 239000004367 Lipase Substances 0.000 abstract description 8
- 102000004882 Lipase Human genes 0.000 abstract description 8
- 108090001060 Lipase Proteins 0.000 abstract description 8
- 235000019421 lipase Nutrition 0.000 abstract description 8
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical class OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 4
- 238000000354 decomposition reaction Methods 0.000 abstract description 4
- 150000002148 esters Chemical class 0.000 abstract description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 abstract description 3
- 239000012346 acetyl chloride Substances 0.000 abstract description 3
- 230000032050 esterification Effects 0.000 abstract description 2
- 238000005886 esterification reaction Methods 0.000 abstract description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 2
- 150000002632 lipids Chemical class 0.000 abstract 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 101000968491 Pseudomonas sp. (strain 109) Triacylglycerol lipase Proteins 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
【発明の詳細な説明】
主粟上型机里公互
プロパギルアルコールの誘導体をトリフルオロメチル基
によって修飾することによって生理活性物質および液晶
化合物が容易且つ高収率で得られる。DETAILED DESCRIPTION OF THE INVENTION Biologically active substances and liquid crystal compounds can be obtained easily and in high yields by modifying derivatives of the main Awagami-type Kishiri-Kotopropargyl alcohol with trifluoromethyl groups.
′ネーおよび 日の” しようとするｐ 占プロパギル
アルコールの誘導体をトリフルオロメチル基によって修
飾することによってトリフルオロメチル基に隣接する炭
素原子上に高い不斉が誘導でき、かつ種々の官能基への
変換を容易におこなうことができる。By modifying a derivative of p-propargyl alcohol with a trifluoromethyl group, a high level of chirality can be induced on the carbon atom adjacent to the trifluoromethyl group, and it is possible to induce various functional groups. can be easily converted.
出発原料として入手容易なプロパギルアルコールとベン
ジルクロリドとを用いエーテル化合物を得る。An ether compound is obtained using easily available propargyl alcohol and benzyl chloride as starting materials.
ＨＣミＣ−ＣＨｚＯＨ＋ ＰｈＣｌ１ｚ（Ｊ！→ＨＣ
＝ Ｃ−ＣＨｚＯＣＨ２Ｐｈさらに得られたエーテル化
物をグリニヤール試薬により金属−水素交換させてアニ
オンへ導き、次にこれにトリフルオロメチル基を導入し
てケトン（１１を得た。HCmiC-CHzOH+ PhCl1z(J!→HC
= C-CHzOCH2Ph Further, the obtained etherified product was subjected to metal-hydrogen exchange using a Grignard reagent to lead to an anion, and then a trifluoromethyl group was introduced thereto to obtain a ketone (11).
得られたケトン（１）は精製が困難であるため、ケトン
ノカルホニル基を還元してアルコール（２）へ誘導した
後単離精製した。Since the obtained ketone (1) was difficult to purify, the ketone nocarbonyl group was reduced to derive alcohol (2), which was then isolated and purified.
得られた光学活性プロパギルアルコール誘導体（２）お
よび（４）の光学分割をおこなった。The optically active propargyl alcohol derivatives (2) and (4) obtained were subjected to optical resolution.
本発明は一般式
（式中ｐｈは置換または未置換フェニル基である）で表
わされるアルコール化合物をエステル化（３）シた後脂
質分解酵素例えばリパーゼで不斉加水分解して、一般式
％式％
（式中ｐｈは上記と同意義を有する）
で表わされる化合物を得る光学活性アルコールの光学分
割法に関するものである。In the present invention, an alcohol compound represented by the general formula (in the formula, ph is a substituted or unsubstituted phenyl group) is esterified (3) and then asymmetrically hydrolyzed with a lipolytic enzyme, such as lipase, to obtain the alcohol compound represented by the general formula %. % (wherein pH has the same meaning as above) The present invention relates to an optical resolution method of an optically active alcohol to obtain a compound represented by % (wherein pH has the same meaning as above).
また、一般式
％式％（４）
（式中ｐｈは上記と同意義である）
で表わされるアルコール化合物についても上記と全く同
様にしてエステル化（５）後脂質分解酵素例えぼりバー
ゼで不斉加水分解して一般式
％式％（４）
（式中ｐｈは上記と同意義を有する）
で表わされる化合物を得る光学活性アルコールの光学分
割法に関するものである。In addition, for the alcohol compound represented by the general formula % formula % (4) (in which pH has the same meaning as above), after esterification (5) in exactly the same manner as above, a lipolytic enzyme, e.g. This invention relates to an optical resolution method of an optically active alcohol to obtain a compound represented by the general formula % (4) (wherein pH has the same meaning as above) by hydrolysis.
光学活性アルコールの光学分割法を説明すれば次のよう
である。The optical resolution method for optically active alcohols is explained as follows.
（Ａ）不斉放水分解用
原料のアルコール化合物（２）をアセタートまたはイソ
ブチラードのエステル（３）に変換後、脂質分解酵素例
えばリパーゼＭＹおよびリパーゼＰなどで不斉分解する
ことによって、光学活性化合物を得た。(A) After converting the alcohol compound (2), which is a raw material for asymmetric hydrolysis, into an ester of acetate or isobutylade (3), the optically active compound is converted into an optically active compound by asymmetric decomposition using a lipolytic enzyme such as lipase MY and lipase P. Obtained.
（Ｂ）坏肩助ｌり障穎刈
アルコール化合物（２）のラセミ体を例えば還元性ｉで
還元して対応するアルケン（４）にした後、アセタート
またはイソブチラードのエステル（５）に変換後、上記
と同様にして脂質分解酵素例えばリパーゼＭＹおよびリ
パーゼＰなどで不斉分解することによって光学活性化合
物（Ｒ）−（４） 、（Ｓ）−（５）を得た。(B) The racemic form of the alcohol compound (2) is reduced to the corresponding alkene (4), for example with reducing i, and then converted to the acetate or isobutylade ester (5), Optically active compounds (R)-(4) and (S)-(5) were obtained by asymmetric decomposition using lipolytic enzymes such as lipase MY and lipase P in the same manner as above.
Ｒ
π
および
（５）′
次に実施例を掲げて本発明を説明するが、これに限定さ
れるものではない。R π and (5)′ Next, the present invention will be explained with reference to Examples, but the present invention is not limited thereto.
実施例
２Ｐｈ
）１２Ｐｈ
ａ）アセタート （３）の合成
窒素気流下減圧でよく乾燥させた５０ｍ７！の三つロフ
ラスコに、塩化メチレン１５ｍ１１アルコ−ル（２１１
，２２ｇ （５，００ｍｍｏｆｆ）ならびに塩化アセチ
ル０．４３ ｍｌ （６，０５ｍｍｏｌ）を加え、氷浴
シこより冷却した。ここに、ピリジン０．４９ｍｊ！（
６，０６ｍｍｏｊ！ ）を滴下し、室温に戻して終夜攪
陣を行なった。１規定の塩酸水溶液を加えて反応を停止
させ、塩化メチレンで抽出後、飽和炭酸水素ナトリウム
水溶液で洗浄し、無水硫酸マグネシウムで乾燥させた。Example 2 Ph) 12 Ph a) Acetate Synthesis of (3) 50 m7 well dried under reduced pressure under a nitrogen stream! In a three-necked flask, add 15 ml of methylene chloride and 11 alcohol (211
, 22 g (5,00 mmoff) and 0.43 ml (6,05 mmol) of acetyl chloride were added, and the mixture was cooled in an ice bath. Here, 0.49 mj of pyridine! (
6,06 mmoj! ) was added dropwise, the mixture was returned to room temperature, and stirred overnight. The reaction was stopped by adding a 1N aqueous hydrochloric acid solution, extracted with methylene chloride, washed with a saturated aqueous sodium bicarbonate solution, and dried over anhydrous magnesium sulfate.
溶媒を減圧上留去したのち、カラムクロマトグラフィー
により精製を行ない、目的とするアセタートを１．２８
１
ｇ （４，４７ｍｍｏｎ、８９％ｙｉｅｌｄ）を得た。After distilling off the solvent under reduced pressure, purification was performed by column chromatography to obtain the desired acetate at a concentration of 1.28
1 g (4.47 mmon, 89% yield) was obtained.
’ＨＮＭＲ（ＣＣｌ 、） δ２．１７（ｓ、 ３！
（、ＣｔＬ＋Ｃ（０） ）４．１５（ｄ、 ２Ｈ，ＪＨ
−ｏ ＝１．１Ｈｚ。'HNMR (CCl,) δ2.17 (s, 3!
(, CtL+C(0) )4.15(d, 2H, JH
−o = 1.1Hz.
Ｃ三ＣＣＨ２）、４．５７（ｓ、 ２Ｈ。C3CCH2), 4.57 (s, 2H.
ＣＨ２Ｐｈ ”）、５．８４（ｍ、 ＬＨ。CH2Ph”), 5.84 (m, LH.
ＣＦ、Ｃ，Ｈ（０１（） ）、７．６７（ｓ、 ５Ｈ。CF, C, H (01()), 7.67(s, 5H.
ｐｈ ＞
１９Ｆ ＮＭＲ（Ｃ（Ｊ！ 、） δ−１，８３（ｄ
、 ＪＨ−Ｆ −６，２Ｈｚ ）ＩＲ（ｎｅａｔ ）
３０５０．２８５０（ＣＨ２，ＣＨ）、１７６０
（Ｃ＝Ｏ） ｃｍ−’
なお、対応するイソブチラードについてもアセタートの
場合と全く同様に合成した。収率９９％。ph > 19F NMR (C(J!,) δ-1,83(d
, JH-F -6,2Hz)IR(neat)
3050.2850 (CH2, CH), 1760
(C=O) cm-' The corresponding isobutylade was also synthesized in exactly the same manner as in the case of acetate. Yield 99%.
’ＨＮＭＲ（ＣＣｊｌ！ ４．） δ１．２７（ｄ、
６Ｈ，ＪＨ−ｏ ＝６．８Ｈｚ。'HNMR (CCjl! 4.) δ1.27 (d,
6H, JH-o = 6.8Hz.
ｔｊｊ３）、２．６７（ｓｅｐ、、 ＩＨ，（ＣＨ：＋
）＋４．１５（ｄ、 ２■＋ＪＨ−ｏ ＝２．３Ｈｚ＋
ＣミＣＣＨ２）、４．５５（ｓ、 ２Ｈ。tjj3), 2.67(sep,, IH, (CH:+
)+4.15(d, 2■+JH-o =2.3Hz+
CmiCCH2), 4.55(s, 2H.
ＣＨ２Ｐｈ ）、５．８７（ｍ、 ＬＨ。CH2Ph), 5.87 (m, LH.
ＣＦ２Ｃｌ（ＯＨ） ）、７．３３（ｓ、 ５Ｈ。CF2Cl(OH)), 7.33(s, 5H.
ｐｈ ＞
１９Ｆ ＮＭＲ（ＣＣＩｌ、） δ−０，８３（ｄ、
ＪＨ−ｒ ＝５．６Ｈｚ ）ＩＲ（ｎｅａ’ｔ ）
３０００．２９５０（ＣＨ３，ＣＩ（２，ＣＨ）
、１７６０（Ｃ＝Ｏ） ｃｍ”
ｂ）アセタート（３）の不斉加水分解
５００ｍｎのナス型フラスコにアセタート（３）６．９
６４ ｇ （２４，３ｍｍｏ６）とリパーゼＭＹ８．１
ｇ （２４３０００ｕｎｉｔｓ）ならびに蒸留水３００
ｍｊ！を加え、恒温槽で４０−４１℃に保ちながら攪拌
を続けた。加水分解が進行するにつれて系内に酢酸が生
成してくるが、これを・１規定の水酸化ナトリウム水溶
液で滴定しながら加水分解の進行度をチエツクした。適
当な加水分解率が得られたところで、反応溶液をセライ
ト濾過したのちに酢酸エチルで抽出を行なった。無水硫
酸マグネシウムで乾、ＣＨ）、燥、低沸点物を減圧留去
し、粗生成物をシリカゲルカラムクロマトグラフィーに
より精製し、対応するアルコール（２）１．０９９ ｇ
（４，５０ｍｍｏ１１光学純度８８％ｅｅ＋ ［αコ
Ｄ−１．６８° （Ｃ１，’ＩＯ１ＭｅＯＨ） ）なら
びにアセターＨ３）４．８６７ ｇ （１７，０ｍｍｏ
（１、［α］ｏ＋１６．１０° （ｃ １．２６ 、
ＭｅＯＨ））を得たく回収率８８％）。なお、加水分解
酵素としてリパーゼＰをもちいた場合なども、すべて同
様に行なった。結果は、下表に示した。ph > 19F NMR (CCIl,) δ-0,83 (d,
JH-r=5.6Hz)IR(nea't)
3000.2950(CH3,CI(2,CH)
, 1760 (C=O) cm” b) Asymmetric hydrolysis of acetate (3) Acetate (3) 6.9 in a 500 mn eggplant-shaped flask
64 g (24,3 mmo6) and lipase MY8.1
g (243,000 units) and distilled water 300
mj! was added, and stirring was continued while maintaining the temperature at 40-41°C in a constant temperature bath. As hydrolysis progresses, acetic acid is produced in the system, and the progress of hydrolysis was checked while titrating this with a 1N aqueous sodium hydroxide solution. When a suitable hydrolysis rate was obtained, the reaction solution was filtered through Celite and then extracted with ethyl acetate. Dry over anhydrous magnesium sulfate (CH), remove low boilers under reduced pressure, and purify the crude product by silica gel column chromatography to obtain 1.099 g of the corresponding alcohol (2).
(4,50mmo11 optical purity 88%ee+ [αcoD-1.68° (C1,'IO1MeOH)) and aceter H3) 4.867 g (17,0mmo
(1, [α]o+16.10° (c 1.26,
MeOH)) was obtained with a recovery rate of 88%). The same procedure was also carried out when lipase P was used as the hydrolytic enzyme. The results are shown in the table below.
アセタート リパーゼＭＹ ２７
８８（Ｒ）アセタート リパーゼＰ ３７
５０（Ｓ）イソブチレート リパーゼＭＹ
３１ ４０（β）イソブチレート
リパーゼＰ ２０ ８４（Ｓ）１’Ｈ
Ｉ
よく乾燥した５０ｍ１の三つロフラスコに、窒素気流下
でＮａＡ ｊ！ Ｈ２（ＯＣＩ（ＺＣＨ２０ＣＨ３）
ｚ （ＲｅｄＡ Ｉｌ■）の３、２ Ｍ ）ルエン溶液
２．９ ｍｌ （１０ｍｍｏｌ）ならびに乾燥したジエ
チルエーテル１０ｍｊ２を加えて水浴で冷却した。ここ
に、アルコール（２１１，２２ｇ（５，ＯＯｍｍｏｊ２
）を滴下して、この温度で１０分間、さらに室温で終
夜攪拌を続けた。１規定の塩酸水溶液を加えて反応を停
止させ、エーテル抽出、無水硫酸マグネシウムで乾燥、
溶媒の減圧留去を行なった。粗生成物をシリカゲルカラ
ムクロマトグラフィーにより精製しくｎ−ヘキサン／酢
酸エチル＝２／１） 、期待する化合物を８０％の収率
で得た。Acetate lipase MY 27
88(R) Acetate Lipase P 37
50(S) Isobutyrate Lipase MY
31 40(β)isobutyrate
Lipase P 20 84(S)1'H
I In a well-dried 50 ml three-necked flask, add NaA j! under a stream of nitrogen. H2(OCI(ZCH20CH3)
2.9 ml (10 mmol) of a 3.2 M) toluene solution of z (RedA Il■) and 10 mj2 of dry diethyl ether were added, and the mixture was cooled in a water bath. Here, alcohol (211,22g (5,OOmmoj2
) was added dropwise, and stirring was continued at this temperature for 10 minutes and then at room temperature overnight. The reaction was stopped by adding 1N aqueous hydrochloric acid solution, extracted with ether, dried over anhydrous magnesium sulfate,
The solvent was distilled off under reduced pressure. The crude product was purified by silica gel column chromatography (n-hexane/ethyl acetate = 2/1) to obtain the expected compound in a yield of 80%.
’ＨＮＭＲ（ＣＣβ４） δ３．９４（ｂｓ、 ＩＨ，
ＯＨ） 、４．２０（ｄ＋ ２ＨＩＪＨ−Ｈ，＝５−４
Ｈ２ＩＣＨ＝Ｃ１ｌＣＨｚ ） 、４．４７（ｍ、
ＩＨ。'HNMR (CCβ4) δ3.94 (bs, IH,
OH), 4.20(d+2HIJH-H,=5-4
H2ICH=C1lCHz), 4.47(m,
IH.
ＣＦ３Ｃ１（（ＯＨ） ）、４．７３（ｓ、 ２Ｈ。CF3C1 ((OH)), 4.73(s, 2H.
ＣＨ２Ｐｈ ）、６．０５（ａｄ、 Ｉｎ。CH2Ph), 6.05 (ad, In.
ＪＨ−１（＝５．３，１６．５Ｈｚ、 ＣＦｉＣＨＣ１
ｉ□ ）、６．３７（ｄｔ、 ＪＨ−Ｈ＝５．４．１６
．５）１ｚ。JH-1 (=5.3, 16.5Hz, CFiCHC1
i□), 6.37 (dt, JH-H=5.4.16
．． 5) 1z.
ＣＦＩＣＨＣＨ−ＣＨ） 、７．６８（ｓ、 ５Ｈ。CFICHCH-CH), 7.68 (s, 5H.
Ｐｈ ）
Ｉ９Ｆ ＮＭＲ（ＣＣβ４） δ０．７５（ｄ、 ＪＨ
−Ｆ −６，６Ｈｚ ）ＩＲ（ｎｅａｔ ） ３
４００（Ｏ）１）、３０５０．２８８０（Ｃ）１２．Ｃ
［）、９８０（Ｃ＝Ｃｔｒａｎｓ） ｃｍ−’【
許
＋ ＣＦａＣＨ−ＣＨ＝ＣＨ−ＣＨｚＯＣＨｚＰｈ（
Ｓ） −（５）
ａ）アセタート （５）の合成
アセタート（３）の場合と同様にして、アルコール（４
１０，９８５ｇ （４，ＯＯｍｍｏｆｆｉ） 、塩化ア
セチル０．３４ ｍｌ （４，８０ｍｍｏｊ２）を塩化
メチレン１０ｍ１にｔ容解させ、０℃においてとリジン
０．３９ｍ１（４，８０ｍｍｏｆｆ）を加え、室温に戻
した後終夜攪拌した。ｌ規定の塩酸水溶液を加えて反応
を停止させ、飽和の炭酸水素ナトリウム水溶液で洗浄し
た後、無水硫酸マグネシウムで乾燥させ、溶媒を減圧留
去した。粗生成物をシリカゲルカラムクロマトグラフィ
ーで精製して、望むアセタート（５）を７６％の収率で
得た。Ph) I9F NMR (CCβ4) δ0.75 (d, JH
-F -6,6Hz)IR(neat)3
400(O)1), 3050.2880(C)12. C
[), 980 (C=Ctrans) cm-'[ ＋ CFaCH-CH=CH-CHzOCHzPh(
S) -(5) a) Synthesis of acetate (5) In the same manner as in the case of acetate (3), alcohol (4
10,985 g (4,00 mmoff) and 0.34 ml (4,80 mmoff) of acetyl chloride were dissolved in 10 ml of methylene chloride, and at 0°C, 0.39 ml (4,80 mmoff) of lysine was added and the mixture was returned to room temperature. After that, the mixture was stirred overnight. The reaction was stopped by adding a normal aqueous solution of hydrochloric acid, washed with a saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The crude product was purified by silica gel column chromatography to obtain the desired acetate (5) in 76% yield.
’ＨＮＭＲ（ＣＣ１４） ６２．２５（ｓ、３Ｈ，Ｃ
Ｈ，ｃｏ）、４．２５（ｄ、 ２Ｈ，Ｊ、−ｏ ＝５．
３Ｈｚ。'HNMR (CC14) 62.25 (s, 3H, C
H, co), 4.25 (d, 2H, J, -o = 5.
3Hz.
ＣＨ＝ＣＨＣ１（ｚ ） 、４．７５（’ｓ、 ２Ｈ。CH=CHC1(z), 4.75('s, 2H.
ＣＨ，ｐｈ ）、６．０５（ｄｄ、 ｉＨ。CH, ph), 6.05 (dd, iH.
Ｊｏ−ｏ ＝８．１．１５．６Ｈ２，ＣＦＩＣＨ（ＪＩ
＝ ）、５．９６（ｍ、 ＬＨ，ＣＦ３ＣＨ） 、６
．４２（ｄｔ、 Ｊｌｌ−Ｈ□５．３，１５．６Ｈｚ
。Jo-o =8.1.15.6H2, CFICH(JI
= ), 5.96 (m, LH, CF3CH), 6
．． 42 (dt, Jll-H□5.3, 15.6Hz
.
ＣＨ＝ＣＨＣ１（＝ＣＨ） 、７．７０（５Ｉ５Ｒ。CH=CHC1 (=CH), 7.70 (5I5R.
ｐｈ ）
！９Ｆ ＮＭＲ（ＣＣｆｆｉ 、、） δ−１，８
３（ｄ、 Ｊｏ−ｙ ＝８．１）１ｚ ）ＩＲ（ｎｅ
ａｔ ） ３０５０．２９００ （ＣＨＺ 、
ＣＨ）、１７６０（Ｃ＝Ｏ） 、９７０（Ｃ＝Ｃｔ
ｒａｎｓ） ａｍ−’ｂ）アセタート （５）の）
■ ゝ” ひ５０ｍβのナス型フラスコにアセター）
＋５１０．９００ｇ （３，００ｍｍｏｎりとリパーゼ
ＭＹ０．５４ｇ（１６２００ｕｎｉｔｓ ）ならびに蒸
留水３０ｍｆｆを加え、恒温槽で４０−４１°Ｃに保ち
ながら攪拌を続けた。ph)! 9F NMR (CCffi, ) δ-1,8
3(d,Jo-y =8.1)1z)IR(ne
at) 3050.2900 (CHZ,
CH), 1760 (C=O), 970 (C=Ct
rans) am-'b) acetate (5))
■ ゝ” Acetar in a 50mβ eggplant-shaped flask)
+510.900 g (3,00 mm) of lipase MY0.54 g (16,200 units) and 30 mff of distilled water were added, and stirring was continued while maintaining the temperature at 40-41°C in a constant temperature bath.
加水分解が進行するにつれて系内に酢酸が生成してくる
が、これを１規定の水酸化ナトリウム水溶液で滴定しな
がら加水分解の進行度をチエツクした。およそ３０％の
加水分解率が達成されたところで、反応溶液をセライト
濾過したのちに酢酸工□チルで抽出を行なった。無水硫
酸マグネシウムで乾燥、低沸点物を減圧留去し、粗生成
物をシリカゲルカラムクロマトグラフィーにより精製し
、対応するアルコール（Ｒ）−（４） ０．１７４
ｇ （０，７１ｍｍｏｆ！ｓ光学純度８８％ｅｅｓ［α
］Ｄ＋７．９１゜（ｃ １．２３ 、ＭｅＯＨ） ）な
らびにアセタート（Ｓ）−（５）０．５７３ ｇ （１
，９９ｍｍｏ＃）を得た（回収率９０％）。As hydrolysis progresses, acetic acid is produced in the system, and the progress of hydrolysis was checked while titrating this with a 1N aqueous sodium hydroxide solution. When a hydrolysis rate of approximately 30% was achieved, the reaction solution was filtered through Celite and then extracted with ethyl acetate. Dry over anhydrous magnesium sulfate, remove low-boiling substances under reduced pressure, and purify the crude product by silica gel column chromatography to obtain the corresponding alcohol (R)-(4) 0.174
g (0,71 mmof!s optical purity 88%ees [α
] D + 7.91° (c 1.23 , MeOH) ) and acetate (S)-(5) 0.573 g (1
, 99 mmo#) was obtained (recovery rate 90%).
又里少羞果
出発原料として入手容易なプロパギルアルコールから誘
導された光学活性アルコール（ラセミ体）を脂質分解酵
素により高収率で光学分割することができた。An optically active alcohol (racemate) derived from propargyl alcohol, which is readily available as a starting material, could be optically resolved in high yield using a lipolytic enzyme.
Claims (2)
分解酵素で不斉加水分解して、 一般式 ▲数式、化学式、表等があります▼−（２） および ▲数式、化学式、表等があります▼−（３） （式中Ｐｈは上記と同意義を有する） で表わされる化合物を得ることを特徴とする光学活性ア
ルコールの光学分割法。(1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (2) (In the formula, Ph is a substituted or unsubstituted phenyl group) After esterifying the alcohol compound, it is asymmetrically hydrolyzed with a lipolytic enzyme. Compounds represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼-(2) and ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼-(3) (In the formula, Ph has the same meaning as above) An optical resolution method for an optically active alcohol, characterized in that it obtains the following:
分解酵素で不斉加水分解して一般式▲数式、化学式、表
等があります▼−（４） および ▲数式、化学式、表等があります▼−（５） （式中Ｐｈは上記と同意義を有する） で表わされる化合物を得ることを特徴とする光学活性ア
ルコールの光学分割法。(2) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (4) (In the formula, Ph has the same meaning as above) After esterifying the alcohol compound, it is asymmetrically hydrolyzed with a lipolytic enzyme. To obtain a compound represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼-(4) and ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼-(5) (In the formula, Ph has the same meaning as above) An optical resolution method for optically active alcohols.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29218387A JPH01137996A (en) | 1987-11-20 | 1987-11-20 | Optical resolution of optically active alcohol |
| US07/396,421 US5047346A (en) | 1987-11-20 | 1989-08-21 | Optically active 3-(2-trifluoro-1-hydroxyethyl)propenyl benzyl ether, derivatives thereof, method for preparing the same and use thereof for liquid crystal compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29218387A JPH01137996A (en) | 1987-11-20 | 1987-11-20 | Optical resolution of optically active alcohol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01137996A true JPH01137996A (en) | 1989-05-30 |
Family
ID=17778635
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29218387A Pending JPH01137996A (en) | 1987-11-20 | 1987-11-20 | Optical resolution of optically active alcohol |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01137996A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5097075A (en) * | 1989-10-16 | 1992-03-17 | Showa Shell Sekiyu Kabushiki Kaisha | 1,1,1-trifluoro-2-hydroxy compound |
| EP0714984A2 (en) | 1994-11-29 | 1996-06-05 | The Nisshin Oil Mills, Ltd. | Process for producing optically active alcohol containing phenyl group |
-
1987
- 1987-11-20 JP JP29218387A patent/JPH01137996A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5097075A (en) * | 1989-10-16 | 1992-03-17 | Showa Shell Sekiyu Kabushiki Kaisha | 1,1,1-trifluoro-2-hydroxy compound |
| EP0714984A2 (en) | 1994-11-29 | 1996-06-05 | The Nisshin Oil Mills, Ltd. | Process for producing optically active alcohol containing phenyl group |
| US5600027A (en) * | 1994-11-29 | 1997-02-04 | The Nisshin Oil Mills, Ltd. | Process for producing optically active alcohol containing phenyl group |
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