JPH0641443B2 - Method for producing optically active amino acid - Google Patents
Method for producing optically active amino acidInfo
- Publication number
- JPH0641443B2 JPH0641443B2 JP61049249A JP4924986A JPH0641443B2 JP H0641443 B2 JPH0641443 B2 JP H0641443B2 JP 61049249 A JP61049249 A JP 61049249A JP 4924986 A JP4924986 A JP 4924986A JP H0641443 B2 JPH0641443 B2 JP H0641443B2
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- group
- amino acid
- formula
- active amino
- 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 - Lifetime
Links
- 150000001413 amino acids Chemical class 0.000 title claims description 10
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 16
- 150000001869 cobalt compounds Chemical class 0.000 claims description 9
- -1 diphenylphosphino Chemical group 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 8
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 150000002466 imines Chemical class 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 238000006317 isomerization reaction Methods 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- MERDFPRZMPWARC-UHFFFAOYSA-N (1-diphenylphosphanyl-3-phenylpropan-2-yl)-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CC(P(C=1C=CC=CC=1)C=1C=CC=CC=1)CC1=CC=CC=C1 MERDFPRZMPWARC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000002262 Schiff base Substances 0.000 description 10
- 150000004753 Schiff bases Chemical class 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 5
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 5
- 239000004474 valine Substances 0.000 description 5
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910017052 cobalt Inorganic materials 0.000 description 3
- 239000010941 cobalt Substances 0.000 description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- JJJCPLVECNLEDT-YTTGMZPUSA-N [(1r)-2-diphenylphosphanyl-1-phenylethyl]-diphenylphosphane Chemical compound C=1C=CC=CC=1P([C@@H](CP(C=1C=CC=CC=1)C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 JJJCPLVECNLEDT-YTTGMZPUSA-N 0.000 description 2
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- ROBXZHNBBCHEIQ-BYPYZUCNSA-N ethyl (2s)-2-aminopropanoate Chemical compound CCOC(=O)[C@H](C)N ROBXZHNBBCHEIQ-BYPYZUCNSA-N 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 150000003003 phosphines Chemical group 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- JETBVOLWZWPMKR-UHFFFAOYSA-N (1-carboxy-2-methylpropyl)azanium;chloride Chemical compound Cl.CC(C)C(N)C(O)=O JETBVOLWZWPMKR-UHFFFAOYSA-N 0.000 description 1
- NUOYJPPISCCYDH-BYPYZUCNSA-N (2s)-1-(2,2,2-trifluoroacetyl)pyrrolidine-2-carbonyl chloride Chemical compound FC(F)(F)C(=O)N1CCC[C@H]1C(Cl)=O NUOYJPPISCCYDH-BYPYZUCNSA-N 0.000 description 1
- VTVJMWZZVJSEMO-BYPYZUCNSA-N (2s)-pyrrolidine-2-carbonyl chloride Chemical compound ClC(=O)[C@@H]1CCCN1 VTVJMWZZVJSEMO-BYPYZUCNSA-N 0.000 description 1
- RBPMGSWTAMFXNZ-UHFFFAOYSA-N 1-nitroethanamine Chemical compound CC(N)[N+]([O-])=O RBPMGSWTAMFXNZ-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000004716 alpha keto acids Chemical class 0.000 description 1
- UAMZETBJZRERCQ-UHFFFAOYSA-N alpha-aminopropionitrile Chemical compound CC(N)C#N UAMZETBJZRERCQ-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- PQGVTLQEKCJXKF-RGMNGODLSA-N ethyl (2s)-2-amino-3-methylbutanoate;hydron;chloride Chemical compound Cl.CCOC(=O)[C@@H](N)C(C)C PQGVTLQEKCJXKF-RGMNGODLSA-N 0.000 description 1
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- GEMHFKXPOCTAIP-UHFFFAOYSA-N n,n-dimethyl-n'-phenylcarbamimidoyl chloride Chemical compound CN(C)C(Cl)=NC1=CC=CC=C1 GEMHFKXPOCTAIP-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000003507 refrigerant Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000005891 transamination reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、光学活性アミノ酸、更に詳細には次の一般式
(I)、 （式中、Ｒ１は水素又は炭素数１〜４のアルキル基、Ｒ
２は水素、炭素数１〜４のアルキル基、フェニル基又は
ヒドロキシフェニル基を示す）で表わされる光学活性ア
ミノ酸の製造法に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an optically active amino acid, more specifically, the following general formula:
(I), (In the formula, R 1 represents hydrogen or an alkyl group having 1 to 4 carbon atoms, R 1
2 represents hydrogen, an alkyl group having 1 to 4 carbon atoms, a phenyl group or a hydroxyphenyl group) and relates to a method for producing an optically active amino acid.
従来、光学活性アミノ酸を得るには、化学的にdl-体を
合成し、それを化学的に、あるいは酵素や微生物を利用
して両者を分離する方法がとられている。しかしながら
化学的にdl-体を分離する方法は非常に煩瑣な上、分離
した不必要な方の異性体をどのように再利用するか等の
問題があつた。一方酵素や微生物を利用する方法では、
反応条件あるいは培養条件がきわめて厳格な上、常に変
性や有害菌汚染等により、活性が低下する危険性があつ
た。Conventionally, in order to obtain an optically active amino acid, a method of chemically synthesizing a dl-form and separating it chemically or by utilizing an enzyme or a microorganism has been used. However, the method of chemically separating the dl-form is very complicated, and there are problems such as how to reuse the separated unnecessary isomer. On the other hand, in the method using enzymes and microorganisms,
The reaction conditions or culture conditions were extremely strict, and there was a risk that the activity would always be lowered due to denaturation or contamination with harmful bacteria.
〔発明が解決しようとする問題点〕 従つて、不斉合成等により化学的に光学活性アミノ酸の
一方のみを選択的又は優勢に製造し、dl-体の分離操作
を省略あるいは軽減できるような方法の開発が望まれて
いた。[Problems to be Solved by the Invention] Accordingly, a method in which only one of the optically active amino acids is chemically or selectively produced by asymmetric synthesis or the like, and the separation operation of the dl-form can be omitted or reduced. Was desired to be developed.
このような実状において、本発明者は鋭意研究を行つた
結果、原料として、後記式(II)で表わされる特定のシツ
フ塩基、すなわちＸが電子吸引基であるシツフ塩基を使
用し、コバルト化合物、特定の光学活性第３級ホスフィ
ン及び還元剤よりなる触媒の存在下加熱すれば、不斉異
性化が生起して光学活性イミン化合物が生成されるこ
と、そしてこれを加水分解すれば光学活性アミノ酸が得
られることを見出し、本発明を完成した。In such an actual situation, the present inventor has conducted extensive studies, and as a raw material, a specific Schiff base represented by the following formula (II), that is, a Schiff base in which X is an electron-withdrawing group, is used, and a cobalt compound, When heated in the presence of a catalyst consisting of a specific optically active tertiary phosphine and a reducing agent, asymmetric isomerization occurs and an optically active imine compound is produced, and when this is hydrolyzed, an optically active amino acid is produced. The inventors have found that they can be obtained and completed the present invention.
本発明方法は次の反応式によつて示される。The method of the present invention is shown by the following reaction formula.
（式中、Ｒ３は炭素数１〜４のアルキル基、Ｒ４は水素
又は炭素数１〜４のアルキル基、Ｘはフェニル基、ニト
ロ基、シアノ基又は低級アルコキシカルボニル基を示
し、Ｒ１及びＲ２は前記と同じものを示す） すなわち、本発明は、シツフ塩基(II)を、2,3-0-イソプ
ロピリデン-2,3-ジヒドロキシ-1,4-ビス（ジフェニルホ
スフィノ）ブタン（以下、「DIOP」と略称する）、2,
2′−ビス（ジフェニルホスフィノ）-1,1′−ビナフチ
ル（以下、「BINAP」と略称する）及び1-ベンジル-1,2-
ビス（ジフェニルホスフィノ）エタン（以下、「phenph
os」と略称する）から選ばれる光学活性第３級ホスフィ
ン、コバルト化合物、及び還元剤よりなる触媒の存在下
不斉異性化して光学活性イミン化合物(III)となし、次
いでこれを加水分解して光学活性アミノ酸(I)を製造す
る方法である。 (In the formula, R 3 represents an alkyl group having 1 to 4 carbon atoms, R 4 represents hydrogen or an alkyl group having 1 to 4 carbon atoms, X represents a phenyl group, a nitro group, a cyano group or a lower alkoxycarbonyl group, and R 1 And R 2 are the same as above) That is, the present invention provides Schiff base (II) with 2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis (diphenylphosphino) butane. (Hereinafter, abbreviated as "DIOP"), 2,
2'-bis (diphenylphosphino) -1,1'-binaphthyl (hereinafter abbreviated as "BINAP") and 1-benzyl-1,2-
Bis (diphenylphosphino) ethane (hereinafter "phenph
abbreviated as "os") to asymmetrically isomerize in the presence of a catalyst consisting of an optically active tertiary phosphine, a cobalt compound, and a reducing agent to give an optically active imine compound (III), which is then hydrolyzed. A method for producing an optically active amino acid (I).
本反応は、触媒的不斉トランスアミネーシヨンというべ
き文献未記載の新しい反応であり、光学活性アミノ酸
(I)の製造はもとより、(IV)式で表わされるカルボニル
化合物やα−ケト酸の製造にも使用できるものである。This reaction is a new reaction not described in the literature, which should be called catalytic asymmetric transamination.
It can be used not only for the production of (I) but also for the production of a carbonyl compound represented by the formula (IV) and an α-keto acid.
以下更に詳細に本発明を説明する。The present invention will be described in more detail below.
本発明の原料であるシツフ塩基(II)は、例えば、(V)式
で表わされるα−ケト酸エステルと(VI)式で表わされる
第１級アミンとを水抜き装置を付した容器を用いベンゼ
ン溶媒中で還流することにより容易に得られる （式中、Ｒ１，Ｒ２，Ｒ３，Ｒ４及びＸは前記と同じも
のを示す） α−ケト酸エステルとしては、例えばα−ケトプロピオ
ン酸メチル、α−ケト酪酸エチル、α−ケト−β−メチ
ル酪酸イソプロピル、α−ケト−β−メチルパレリアン
酸メチル、α−ケト−γ−メチルパレリアン酸エチル、
α−ケト−β−フエニルプロピオン酸イソプロピル、α
−ケト−β−フェニル酪酸メチル、α−ケト−β−（ｐ
−ヒドロキシフエニル）プロピオン酸メチル等が、また
第一級アミン(VI)としては、例えばベンジルアミン、α
−フエニルエチルアミン、α−ニトロエチルアミン、α
−シアノエチルアミン、グリシンエチルエステル、アラ
ニンエチルエステル等が用いられる。The Schiff base (II) which is the raw material of the present invention uses, for example, a container equipped with a drainer for the α-keto acid ester represented by the formula (V) and the primary amine represented by the formula (VI). Easily obtained by refluxing in benzene solvent (In the formula, R 1 , R 2 , R 3 , R 4 and X are the same as described above) Examples of the α-keto acid ester include, for example, methyl α-ketopropionate, ethyl α-ketobutyrate and α-keto. -Β-Methylbutyric acid isopropyl, α-keto-β-methylpalerlianate methyl, α-keto-γ-methylpalerianate ethyl,
α-keto-β-phenylpropionate isopropyl, α
-Methyl keto-β-phenylbutyrate, α-keto-β- (p
-Hydroxyphenyl) methyl propionate and the like, and as the primary amine (VI), for example, benzylamine, α
-Phenylethylamine, α-nitroethylamine, α
-Cyanoethylamine, glycine ethyl ester, alanine ethyl ester and the like are used.
シツフ塩基(II)は、Ｘの電子吸引基を有することが必須
であり、これがないと不斉異性化は円滑に進行しない。It is essential that the Schiff base (II) has an electron withdrawing group of X, and without this, asymmetric isomerization does not proceed smoothly.
また、触媒を構成するコバルト化合物としては、CoC
l2、CoBr2、ヘキシル酸コバルト、オクチル酸コバル
ト、デシル酸コバルト、ナフテン酸コバルト等が；還元
剤としては、HAli-Bu2、Et3Al、BuLi、LiAlH4、LiBH4、
NaBH4、vitride(NaAlH2(OCH2CH2OCH3)2の商品名）等が
挙げられる。また、光学活性第３級ホスフィンであるDI
OP、BINAP及びphenphosのうち、右旋性のものの化学式
を示せば、以下のとおりである。In addition, CoC is used as the cobalt compound constituting the catalyst.
l 2 , CoBr 2 , cobalt hexylate, cobalt octylate, cobalt decylate, cobalt naphthenate, etc .; as reducing agents, HAli-Bu 2 , Et 3 Al, BuLi, LiAlH 4 , LiBH 4 ,
NaBH 4 , vitride (trade name of NaAlH 2 (OCH 2 CH 2 OCH 3 ) 2 ) and the like can be mentioned. In addition, DI which is an optically active tertiary phosphine
The chemical formulas of dextrorotatory ones among OP, BINAP and phenphos are shown below.
これらのコバルト化合物、光学活性第３級ホスフイン及
び還元剤はそれぞれを混合して使用することができる
が、コバルト化合物と光学活性第３級ホスフインは両者
の錯体、例えばCoLnY2型錯体（Ｌは光学活性第３級ホス
フイン、ｎは１又は２、ＹはCl，Br又酸残基を示す）と
して使用することもできる。上記３成分よりなる触媒
は、コバルト化合物、光学活性第３級ホスフイン及び還
元剤がモル比で１：１〜４：３〜５の割合になるように
構成するのが好ましい。 These cobalt compounds, optically active tertiary phosphines and reducing agents can be used as a mixture, but the cobalt compounds and the optically active tertiary phosphines are both complexes, for example, CoLnY 2 type complex (L is an optical It can also be used as an active tertiary phosphine, n is 1 or 2 and Y is Cl, Br or an acid residue). It is preferable that the catalyst composed of the above three components is constituted so that the cobalt compound, the optically active tertiary phosphine and the reducing agent have a molar ratio of 1: 1 to 4: 3-5.
本発明方法は例えば次の如くして実施される。The method of the present invention is carried out, for example, as follows.
耐圧反応管にコバルト化合物１mMと光学活性第３級ホス
フインを１〜４mMを加えるかまたはCoLnY2を１mM加えた
後、N2置換し有機溶媒（テトラヒドロフラン、トルエン
等が好ましい）２０〜１００mlを加えて均一溶液とす
る。本溶液をドライアイス−アセトン等の冷媒で−２０
℃付近まで冷却し、還元剤１M/lのテトラヒドロフラン
またはトルエン溶液３〜５mlを撹拌下に滴下し、室温に
もどしてさらに0.5〜１時間撹拌する。次いでシツフ塩
基５０〜１５０mMを加え、６０°〜１００℃で数時間〜
２０時間撹拌を続けて、不斉異性反応を行わせる。Add 1 mM of cobalt compound and 1 to 4 mM of optically active tertiary phosphine or 1 mM of CoLnY 2 to a pressure resistant reaction tube, and then replace with N 2 and add 20 to 100 ml of organic solvent (tetrahydrofuran, toluene, etc.). Make a homogeneous solution. This solution is -20 with a refrigerant such as dry ice-acetone.
The mixture is cooled to around 0 ° C., 3 to 5 ml of a tetrahydrofuran or toluene solution containing 1 M / l of a reducing agent is added dropwise with stirring, the temperature is returned to room temperature, and the mixture is further stirred for 0.5 to 1 hour. Then add Schiff's base 50-150mM at 60 ° -100 ° C for several hours
The asymmetric isomerization reaction is carried out by continuing stirring for 20 hours.
斯くして得られる光学活性イミン化合物(III)を常法に
よつて加水分解すれば目的の光学活性アミノ酸(I)が得
られる。The desired optically active amino acid (I) can be obtained by hydrolyzing the thus obtained optically active imine compound (III) by a conventional method.
以下に実施例をあげて本発明を更に詳しく説明する。 Hereinafter, the present invention will be described in more detail with reference to examples.
なお不斉収率は、加水分解を緩やかな段階で停止して、
光学活性イミン化合物のアゾメチン結合のみが加水分解
して生成される光学活性アミノ酸エステルを用い、文献
（バイオケミカル・アンド・バイオフイジカル・リサー
チ・コミユニケーシヨンズ（Biochem.Biophys.Res.Comm
un.），１９，３６１（１９６５））記載の方法に従つ
て、Ｎ−トリフルオロアセチル−Ｌ−プロリルペプチド
エステルとして、そのガスクロマトグラフイーのｄ−
体、ｌ−体に相当するピークの面積比により算出した。The asymmetric yield is as follows:
Using an optically active amino acid ester generated by hydrolysis of only the azomethine bond of an optically active imine compound, the literature (Biochemical.Biophys.Res.Comm
un.), 19, 361 (1965)), as a N-trifluoroacetyl-L-prolyl peptide ester, d- of its gas chromatography.
It was calculated by the area ratio of the peaks corresponding to the body and the 1-body.
実施例１ ｌ−体優勢バリンの合成 １００ml容の耐圧反応管にCo((+)DIOP)Cl2６３mg（0.1m
M）を加えＮ２置換後テトラヒドロフラン（以下ＴＨＦ
と略す）１０mlを加えて均一溶液とした。ドライアイス
−アセトン浴で−２０℃まで溶液を冷却しvitrideの0.1
M/lＴＨＦ液４mlを加え、室温に戻して３０分撹拌し
た。これにα−ケト−イソバレリアン酸エチルとベンジ
ルアミンの縮合によつて得たシツフ塩基（分子量２３
３）2.33ｇ（１０mM）を加え、８０℃に加熱して１５時
間反応させた。反応終了後、反応物中の光学活性イミン
化合物をガスクロマトグラフイーにより定量し、化学収
率を算出したところ86.7％であつた。次いで不斉収率を
算出するため上記反応物からＴＨＦを留去した後１０％
HCl１０mlを加え室温で３０分撹拌した。水層部を分液
しエーテル１０mlで１回洗浄後８０℃で減圧乾燥した。
得られた固形分（バリンエチルエステル塩酸塩）のごく
一部（２０〜３０mg）をとり、Ｎ−トリフルオロアセチ
ル−Ｌ−プロリルクロライド0.1M/lCHCl3液0.5mlを加
え、３０分間振盪してＮ−フルオロアセチル−Ｌ−プロ
リルバリンエチルエステルとした。さらにトリエチルア
ミン１mlを加えて過剰のＮ−トリフルオロアセチル−Ｌ
−プロリルクロライドを分解し、水１mlを加えて分液
し、有機層を濃縮してガスクロマトグラフイー（条件：
シリコンOV１０１，２５ｍ，１００°→２５０℃，１０
℃／min昇温）分析を行い、ｄ−体、ｌ−体に相当する
ピークの面積比より不斉収率を算出したところ24.7％で
あつた。Example 1 Synthesis of 1-body predominant valine 63 mg (0.1 m of Co ((+) DIOP) Cl 2 in a 100 ml pressure resistant reaction tube.
M) was added and N 2 was substituted, and then tetrahydrofuran (hereinafter THF)
Abbreviated) 10 ml was added to make a homogeneous solution. Cool the solution to -20 ° C in a dry ice-acetone bath and add 0.1 of vitride.
4 ml of M / l THF solution was added, and the mixture was returned to room temperature and stirred for 30 minutes. A Schiff base (molecular weight 23) obtained by condensing ethyl α-keto-isovalerate with benzylamine was added thereto.
3) 2.33 g (10 mM) was added, and the mixture was heated to 80 ° C. and reacted for 15 hours. After the reaction was completed, the optically active imine compound in the reaction product was quantified by gas chromatography, and the chemical yield was calculated to be 86.7%. 10% after the THF was distilled off from the above reaction product to calculate the asymmetric yield
HCl (10 ml) was added and the mixture was stirred at room temperature for 30 minutes. The aqueous layer was separated, washed once with 10 ml of ether and dried under reduced pressure at 80 ° C.
A small portion (20 to 30 mg) of the obtained solid content (valine ethyl ester hydrochloride) was taken, 0.5 ml of N-trifluoroacetyl-L-prolyl chloride 0.1M / l CHCl 3 solution was added, and the mixture was shaken for 30 minutes. To give N-fluoroacetyl-L-prolyl valine ethyl ester. Further, 1 ml of triethylamine was added to add excess N-trifluoroacetyl-L.
-The prolyl chloride was decomposed, 1 ml of water was added for liquid separation, and the organic layer was concentrated and subjected to gas chromatography (conditions:
Silicon OV101, 25m, 100 ° → 250 ° C, 10
(° C / min temperature increase) analysis was performed, and the asymmetric yield was calculated from the area ratio of the peaks corresponding to the d-form and the 1-form, and was 24.7%.
上記固形分に２０％HCl１０mlを加え、１２０℃で１５
時間加水分解することによりｌ−体優勢バリン塩酸塩が
得られた。Add 10 ml of 20% HCl to the above solid content, and add 15% at 120 ° C.
By time hydrolysis, the 1-form predominant valine hydrochloride was obtained.
実施例２ ｄ−体優勢バリンの合成 実施例１のCo((+)DIOP)Cl2の代りに Co((+)BINAP)Cl2を用い実施例１と同様にして、ｄ−体
優勢バリンを化学収率８８％、不斉収率8.7％で得た。Example 2 Synthesis of d-body-predominant valine In the same manner as in Example 1 except that Co ((+) DIOP) Cl 2 in Example 1 was replaced by Co ((+) BINAP) Cl 2 , d-body-predominant valine was used. Was obtained with a chemical yield of 88% and an asymmetric yield of 8.7%.
実施例３ ｌ−体優勢フエニルアラニンの合成 実施例１のシツフ塩基の代りにα−ケト−β−フエニル
プロピオン酸イソプロピルとベンジリアミンの縮合によ
つて得たシツフ塩基（分子量２９５）を用い実施例１と
同様にして、ｌ−体優勢フエニルアラニンを化学収率８
５％、不斉収率12.8％で得た。Example 3 Synthesis of l-form predominant phenylalanine Performed using the Schiff base (molecular weight 295) obtained by condensation of isopropyl α-keto-β-phenylpropionate and benzyliliamine instead of the Schiff base of Example 1. In the same manner as in Example 1, the 1-form predominant phenylalanine was obtained in a chemical yield of 8
The yield was 5% and the asymmetric yield was 12.8%.
実施例４ ｌ−体優勢バリンの合成 実施例１のシツフ塩基の代りにα−ケト−イソバレリア
ン酸イソプロピルとアラニンエチルエステルの縮合によ
つて得たシツフ塩基（分子量２５７）を、Co((+)DIOP)C
l2の代りに CoCl2と(+)phenphosを各0.1mM用い、実施例１と同様に
して、ｌ−体優勢バリンを化学収率８３％、不斉収率3.
5％で得た。Example 4 Synthesis of 1-body predominant valine Instead of the Schiff base of Example 1, a Schiff base (molecular weight 257) obtained by condensation of isopropyl α-keto-isovalerate and alanine ethyl ester was replaced with Co ((+ ) DIOP) C
Using 0.1 mM each of CoCl 2 and (+) phenphos instead of l 2 and carrying out the same procedure as in Example 1, the chemical yield of valine predominant in 1-form was 83%, and the asymmetric yield was 3.
Got at 5%.
本発明によれば、安価な原料で、簡便な化学的手段によ
り、収率よく光学活性アミノ酸を得ることができる。According to the present invention, an optically active amino acid can be obtained in good yield from inexpensive raw materials by a simple chemical means.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｃ０７Ｂ 61/00 ３００ ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Internal reference number FI technical display location C07B 61/00 300
Claims (2)
ル基、Ｒ２は水素、炭素数１〜４のアルキル基、フェニ
ル基又はヒドロキシフェニル基、Ｒ３は炭素数１〜４の
アルキル基、Ｘはフェニル基、ニトロ基、シアノ基又は
低級アルコキシカルボニル基を示す） で表わされるシッフ塩基を、2,3-0-イソプロピリデン-
2,3-ジヒドロキシ-1,4-ビス（ジフェニルホスフィノ）
ブタン、2,2′−ビス（ジフェニルホスフィノ）-1,1′
−ビナフチル及び1-ベンジル-1,2-ビス（ジフェニルホ
スフィノ）エタンから選ばれる光学活性第３級ホスフィ
ン、コバルト化合物、及び還元剤よりなる触媒の存在下
不斉異性化して一般式(III) （式中、Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＸは前記と同じも
のを示す）で表わされる光学活性イミン化合物となし、
次いでこれを加水分解することを特徴とする一般式(I) （式中、Ｒ１及びＲ２は前記と同じものを示す） で表わされる光学活性アミノ酸の製造法。1. General formula (II) (In the formula, R 1 and R 4 are hydrogen or an alkyl group having 1 to 4 carbon atoms, R 2 is hydrogen, an alkyl group having 1 to 4 carbon atoms, a phenyl group or a hydroxyphenyl group, and R 3 is 1 to 4 carbon atoms. Alkyl group, X represents a phenyl group, a nitro group, a cyano group or a lower alkoxycarbonyl group), 2,3-0-isopropylidene-
2,3-dihydroxy-1,4-bis (diphenylphosphino)
Butane, 2,2'-bis (diphenylphosphino) -1,1 '
-General formula (III) by asymmetric isomerization in the presence of a catalyst consisting of an optically active tertiary phosphine selected from binaphthyl and 1-benzyl-1,2-bis (diphenylphosphino) ethane, a cobalt compound, and a reducing agent. (Wherein R 1 , R 2 , R 3 , R 4 and X are the same as defined above), and the optically active imine compound
Then, the general formula (I) characterized by hydrolyzing it (In the formula, R 1 and R 2 are the same as defined above).
スフィンとの錯体及び還元剤よりなるものである特許請
求の範囲第１項記載の光学活性アミノ酸の製造法。2. The method for producing an optically active amino acid according to claim 1, wherein the catalyst comprises a complex of a cobalt compound and an optically active tertiary phosphine and a reducing agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61049249A JPH0641443B2 (en) | 1986-03-06 | 1986-03-06 | Method for producing optically active amino acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61049249A JPH0641443B2 (en) | 1986-03-06 | 1986-03-06 | Method for producing optically active amino acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62207245A JPS62207245A (en) | 1987-09-11 |
| JPH0641443B2 true JPH0641443B2 (en) | 1994-06-01 |
Family
ID=12825572
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61049249A Expired - Lifetime JPH0641443B2 (en) | 1986-03-06 | 1986-03-06 | Method for producing optically active amino acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0641443B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5710322A (en) * | 1996-03-29 | 1998-01-20 | Hoffmann-La Roche Inc. | Optically active iminocarboxylic acid derivatives |
| CN111036306B (en) * | 2019-11-25 | 2021-06-15 | 中国科学院兰州化学物理研究所 | A kind of cobalt-phosphine catalyst and its preparation method and application |
-
1986
- 1986-03-06 JP JP61049249A patent/JPH0641443B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62207245A (en) | 1987-09-11 |
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