JPH01165559A - Selective racemization of optically active amino acid ester - Google Patents
Selective racemization of optically active amino acid esterInfo
- Publication number
- JPH01165559A JPH01165559A JP32286387A JP32286387A JPH01165559A JP H01165559 A JPH01165559 A JP H01165559A JP 32286387 A JP32286387 A JP 32286387A JP 32286387 A JP32286387 A JP 32286387A JP H01165559 A JPH01165559 A JP H01165559A
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- optically active
- peptide
- acid ester
- racemization
- 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
- -1 amino acid ester Chemical class 0.000 title claims abstract description 25
- 230000006340 racemization Effects 0.000 title claims abstract description 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 22
- 235000008206 alpha-amino acids Nutrition 0.000 claims abstract description 12
- 150000002576 ketones Chemical class 0.000 claims abstract description 9
- 239000002798 polar solvent Substances 0.000 claims abstract description 7
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 3
- 125000005907 alkyl ester group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 abstract description 9
- 239000002994 raw material Substances 0.000 abstract description 8
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 abstract description 7
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 abstract description 7
- 238000010438 heat treatment Methods 0.000 abstract description 7
- 239000002253 acid Substances 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract 1
- 229940024606 amino acid Drugs 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000010647 peptide synthesis reaction Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229960005190 phenylalanine Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- IAOZJIPTCAWIRG-WDEREUQCSA-N (3s)-3-azaniumyl-4-[[(2r)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoate Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-WDEREUQCSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 229930182818 D-methionine Natural products 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
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α−アミノ酸エステルの選択的なラセ
ミ化法に関するものである。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a method for selective racemization of optically active α-amino acid esters.
（従来の技術）
光学活性なアミノ酸エステルは各種ペプチド類の合成出
発原料として有用であるが、一般な合成法によるアミノ
酸エステルはラセミ体であるためこれを適当光学分割等
の手段により、所望の光学活性体を得ることが必要にな
る。(Prior art) Optically active amino acid esters are useful as starting materials for the synthesis of various peptides, but since amino acid esters produced by general synthetic methods are racemic, they can be converted into desired optical properties by means such as appropriate optical resolution. It is necessary to obtain the active form.
ところで、光学分割により得られるもう一方の所望でな
い光学活性体を有効に利用することが望まれるが、その
一つとしてこれを再びラセミ化し光学分割を経て漸時所
望の光学活性体に交換させていく利用法がある。By the way, it is desired to effectively utilize the other undesired optically active substance obtained by optical resolution, and one way to do this is to racemize it again and gradually exchange it with the desired optically active substance through optical resolution. There are many ways to use it.
従来、知られた光学活性α−アミノ酸エステルのラセミ
化法としては、Ｄ−メチオニンエステルをアルデヒドと
反応させて、シプフ塩基とし、次いで加水分解する方法
（特公昭３３−１７５５）光学活性アミノ酸エステルを
アルカリ金属と芳香族炭化水素より成る触媒、あるいは
アルカリを多孔性担体に分散、保持させた触媒に接触さ
せる方法（特開昭５Ｏ−５０３０２）などがある。Conventionally known racemization methods for optically active α-amino acid esters include a method in which D-methionine ester is reacted with aldehyde to form a Schipff base, and then hydrolyzed (Japanese Patent Publication No. 33-1755). There is a method of contacting a catalyst comprising an alkali metal and an aromatic hydrocarbon, or a catalyst in which an alkali is dispersed and held in a porous carrier (Japanese Patent Application Laid-open No. 50302-1983).
さらに光学活性フェニルアラニンエステルのラセミ化方
法として、当該ラセミ化をアルカリ金属アルコラードを
用いアルコール中で加熱して行う方法（米国特許第３９
４１８３１号明細′４ｉ）が知られている。 またケト
ン溶媒中で加熱する方法（特開昭５４−１０９９１２）
も知られている。Furthermore, as a method for racemizing optically active phenylalanine ester, the racemization is carried out by heating in alcohol using an alkali metal alcoholade (US Patent No. 39
No. 41831 specification '4i) is known. Also, a method of heating in a ketone solvent (JP-A-54-109912)
is also known.
しかしながら、これらの公知方法のうち、シッフ塩基を
経由する方法では副反応が生起するので精製を十分に行
う必要がある。また触媒としてアルカリ金属など、又は
アルカリ金属アルコラードを使用する方法では触媒の製
造上、あるいはコスト上聞届があるなど必ずしも工業的
に有利な方法とは言えない。 ケトン溶媒中で加熱する
方法では、ケトンのみあるいは第二の触媒としてハロゲ
ン化水素酸、無機酸、脂肪族カルボン酸、芳香族カルボ
ン酸、有機スルホン酸、有機リン酸、ルイス酸を用いる
。ペプチド合成工業における合成反応系では原料アミノ
酸エステルと生成物ペプチドの共存する場合があり、こ
の系にこの方法を利用した場合、最大の問題は共存する
ペプチドを構成する原料アミノ酸エステル由来のアミノ
酸骨格をもラセミ化すると考えられていたことである。However, among these known methods, the method via Schiff's base causes side reactions and therefore requires sufficient purification. In addition, methods using alkali metals or alkali metal alcolades as catalysts are not necessarily industrially advantageous, as there are concerns regarding catalyst production and cost considerations. In the method of heating in a ketone solvent, only a ketone or a hydrohalic acid, an inorganic acid, an aliphatic carboxylic acid, an aromatic carboxylic acid, an organic sulfonic acid, an organic phosphoric acid, or a Lewis acid are used as the second catalyst. In synthetic reaction systems in the peptide synthesis industry, raw amino acid esters and product peptides may coexist, and when this method is used in this system, the biggest problem is that the amino acid skeleton derived from the raw amino acid esters that make up the coexisting peptides is It was also thought that racemization would occur.
またこの方法では、ケトンのみを用いた場合ラセミ化反
応速度が非常に遅く、長時間の加熱を要するので、生成
物ペプチドが変質する恐れがある。In addition, in this method, when only a ketone is used, the racemization reaction rate is very slow and long heating is required, so there is a risk that the product peptide may be denatured.
そこで第二の触媒としてこれらの酸を添加して反応速度
をあげている。しかし、そのため酸の添加、精製の操作
が加わることになり、やはり工業的に不利である。Therefore, these acids are added as a second catalyst to increase the reaction rate. However, this requires addition of acid and purification operations, which is still industrially disadvantageous.
（発明が解決しようとする問題点）
ペプチド合成工業においては合成反応後、目的の反応で
残った原料のアミノ酸エステルを有効利用するためにこ
れをラセミ化して用いるが、その際従来の方法ではラセ
ミ化触媒に選択性がない、あるいは低いため１、そのま
まラセミ化を行なうと生成物ペプチドを構成する原料ア
ミノ酸エステル由来の骨格をもラセミ化しする恐れがあ
り、原料と生成物であるペプチドを分離後、原料のみを
ラセミ化しなければならなかった。(Problem to be solved by the invention) In the peptide synthesis industry, after the synthesis reaction, the amino acid ester of the raw material remaining from the target reaction is racemized and used in order to effectively utilize it. Because the reaction catalyst has no or low selectivity (1), if racemization is performed directly, there is a risk that the skeleton derived from the raw material amino acid ester that makes up the product peptide may also be racemized, so after separating the raw material and the product peptide, , only the raw materials had to be racemized.
さらにこの時、新たな触媒をを加えてラセミ化した後、
反応終了物を精製してフィードバックしなければならな
い。加えて生成物ペプチドの立体特異的精製製も難かし
い。Furthermore, at this time, after adding a new catalyst and racemizing,
The reaction product must be purified and fed back. In addition, stereospecific purification of the product peptide is difficult.
従ってペプチド合成工業においては、共存するペプチド
の原料であるアミノ酸エステルのみを選択的にラセミ化
する方法が求められていた。Therefore, in the peptide synthesis industry, there has been a need for a method for selectively racemizing only the coexisting amino acid esters that are raw materials for peptides.
本発明は、従来方法の様な繁雑な操作を避け、原料アミ
ノ酸エステルのみをラセミ化する方法を提供するもので
ある。The present invention provides a method for racemizing only the starting amino acid ester, avoiding the complicated operations required in conventional methods.
（問題点を解決するための手段）
本発明者らは上記のように、従来共存する生成物ペプチ
ドをもラセミ化してしまうと考られていた問題を鋭意検
討した結果、驚くべきことに生成物ペプチドをプロトン
酸触媒として用いれば、酸などの他の触媒を添加するこ
となしに迅速に原料アミノ酸エステルをラセミ化できる
こと、及びペプチド中のアミノ酸骨格はほとんどラセミ
化されないことを見出して本発明に到達した。(Means for Solving the Problems) As described above, the present inventors have intensively investigated the problem that was conventionally thought to result in racemization of coexisting product peptides, and have surprisingly found that The present invention was achieved by discovering that if a peptide is used as a protonic acid catalyst, the raw amino acid ester can be rapidly racemized without adding any other catalyst such as an acid, and that the amino acid skeleton in the peptide is hardly racemized. did.
従って、本発明は光学活性α−アミノ酸エステルを極性
溶媒中ペプチド又はその誘導体の存在下で選択的にラセ
ミ化することを特徴とする光学活性α−アミノ酸エステ
ルのラセミ化方法を提供するものである。Therefore, the present invention provides a method for racemizing an optically active α-amino acid ester, which comprises selectively racemizing an optically active α-amino acid ester in the presence of a peptide or a derivative thereof in a polar solvent. .
（作用）
本発明方法によるラセミ化反応は光学活性α−アミノ酸
エステルを極性溶媒中で、側鎖あるいはＣ末端にカルボ
ン酸を持つペプチド又はその誘導体と共存させ、加熱す
ることにより進行する。(Function) The racemization reaction according to the method of the present invention proceeds by allowing an optically active α-amino acid ester to coexist with a peptide or its derivative having a carboxylic acid at the side chain or C-terminus in a polar solvent, and heating the mixture.
本発明方法において、原料として用いられる光学活性α
−アミノ酸エステルとしては特に制限はなく、α−炭素
に水素を持つ中性、塩基性、または酸性アミノ酸のエス
テルが支障なく使用できるまた原料光学活性α−アミノ
酸エステルのエステル部分を構成するアルコール残基と
しては特に制限はなく、溶媒成分、あるいは必要により
使用する酸と反応しないものならばいずれでもよい。In the method of the present invention, optically active α used as a raw material
- There are no particular restrictions on the amino acid ester, and esters of neutral, basic, or acidic amino acids having hydrogen at the α-carbon can be used without any problems.Also, alcohol residues constituting the ester moiety of the raw material optically active α-amino acid ester There are no particular limitations on the solvent, and any solvent may be used as long as it does not react with the solvent components or the acid used if necessary.
極性溶媒としては、好ましくはケトン、さらに好ましく
はメチルイソブチルケトンを使用することができる。こ
れらケトンは反応温度及び反応時間に特に制限がなけれ
ば、その種類は特に限定されることはない。また必ずし
も純粋である必要はなく、反応温度及び反応時間に制限
さえなければ水その他の溶媒を含んでいてもよい。ただ
し水を含むケトン溶媒中では反応は遅くなる傾向にある
側鎖あるいはＣ末端にカルボン酸を持つペプチド又はそ
の誘導体としては、ジペプチド以上のペプチド又はその
誘導体、たとえば、Ｎ−ベンジルオキシカルボニル−し
−ア・スバルチルーし一フェニルアラニン又はその脂肪
族低級アルキルエステルを例示することができる。 添
加量は光学活性α−アミノ酸エステルに対して約０．１
倍モル以上、好ましくは約０． ５ないし約５倍モル程
度である。As the polar solvent, preferably a ketone, more preferably methyl isobutyl ketone can be used. The types of these ketones are not particularly limited as long as there are no particular restrictions on reaction temperature and reaction time. Furthermore, it does not necessarily have to be pure, and may contain water or other solvents as long as there are no restrictions on the reaction temperature and reaction time. However, the reaction tends to be slow in a ketone solvent containing water.Peptides or derivatives thereof that have a carboxylic acid in the side chain or C-terminus include dipeptides or higher peptides or derivatives thereof, such as N-benzyloxycarbonyl- Examples include subalternyl-phenylalanine and aliphatic lower alkyl esters thereof. The amount added is approximately 0.1 per optically active α-amino acid ester.
More than twice the mole, preferably about 0. It is about 5 to about 5 times the mole.
加熱は約４０℃ないし２００℃、好くは９０℃ないし２
００℃の温度範囲内で行うことができる。Heating is about 40°C to 200°C, preferably 90°C to 200°C.
It can be carried out within a temperature range of 00°C.
以下本発明を実施例についてさらに詳しく説明する。Hereinafter, the present invention will be explained in more detail with reference to Examples.
実施例 Ｉ
Ｌ−フェニルアラニンメチルエステル１１．４ｍｍｏｌ
を含むメチルイソブチルケトン５０ｇにカルボベンジル
オキシ−α−Ｌ−アスパルチルーフェニルアラニンメチ
ルエステル９．３ｍｍｏｌを加え、（カルボベンジルオ
キシ−α−Ｌ−アスパルチルーＬ−フェニルアラニンメ
チルエステル／Ｌ−フェニルアラニンメチルエステル−
０，８２）沸点（約１１５℃）で２５分間加熱還流した
。次いで反応液にＩＮ−Ｈ（ｊ水溶液１４ｄ、Ｈ２Ｏ５
０−を加え、水層側にフェニルアラニンメチルエステル
を塩酸塩として分離した。得られたフェニルアラニンメ
チルエステルは収率９７．７％、比旋光度ハｌ：ａ）：
”−０（Ｃ＝２． ｔ１２０ ） テあった。Example I L-phenylalanine methyl ester 11.4 mmol
9.3 mmol of carbobenzyloxy-α-L-aspartyl-phenylalanine methyl ester was added to 50 g of methyl isobutyl ketone containing (carbobenzyloxy-α-L-aspartyl-L-phenylalanine methyl ester/L-phenylalanine methyl ester-
0.82) boiling point (approximately 115°C) for 25 minutes under reflux. Then, IN-H (j aqueous solution 14d, H2O5
0- was added, and phenylalanine methyl ester was separated as a hydrochloride in the aqueous layer side. The obtained phenylalanine methyl ester had a yield of 97.7% and a specific optical rotation of 1:a):
”-0 (C=2.t120) There was.
なおメチルイソブチルケトン側に分離したカルボベンジ
ルオキシ−α−Ｌ−アスパルチルーＬ−フェニルアラニ
ンメチルエステルは収率１００％であり、またメチルイ
ソブチルケトンの着色はほとんどなかった。 カルボベ
ンジルオキシ−α−Ｌ−アスパルチル−し一フェニルア
ラニンメチルエステルのラセミ化、即ちα−Ｌ−アスパ
ルチルーＤ−フェニルアラニンメチルエステル（同時に
脱ベンジルオキシカルボニル化される）の生成量はＨＰ
ＬＣによる分析で１％以下であった。The yield of carbobenzyloxy-α-L-aspartyl-L-phenylalanine methyl ester separated on the methyl isobutyl ketone side was 100%, and there was almost no coloring of the methyl isobutyl ketone. Racemization of carbobenzyloxy-α-L-aspartyl-monophenylalanine methyl ester, that is, the amount of α-L-aspartyl-D-phenylalanine methyl ester (simultaneously debenzyloxycarbonylated) is HP
Analysis by LC showed it to be 1% or less.
実施例２
カルボベンジルオキシ−α−Ｌ−アスパルチルーＬ−フ
ェニルアラニンメチルエステル合成後の反応液、即ちフ
ェニルアラニンメチルエステル３ｍｍｏｌ（Ｄ体／１：
、体−９／１） 、カルボベンジルオキシ−α−Ｌ−ア
スパルチル−し一フェニルアラニンメチルエステル２８
ｍｍｏｌを含むメチルイソブチルケトン１５０ｇ （水
分２．５％）を水との共沸点（約９４℃）にて１２分間
加熱し水分を除いた後、１０分間沸点（約１１５℃）で
加熱還流した。Example 2 Reaction solution after synthesis of carbobenzyloxy-α-L-aspartyl-L-phenylalanine methyl ester, that is, 3 mmol of phenylalanine methyl ester (D form/1:
, body-9/1), carbobenzyloxy-α-L-aspartyl-phenylalanine methyl ester 28
150 g of methyl isobutyl ketone containing mmol (2.5% water) was heated for 12 minutes at the azeotropic point with water (approximately 94°C) to remove water, and then heated under reflux at the boiling point (approximately 115°C) for 10 minutes.
反応終了後、反応液中のフェニルアラニンメチルエステ
ルをＨＰＬＣにて分析したところ、収率９５％、エナン
チオマー過剰率０．７％であった。After the reaction was completed, phenylalanine methyl ester in the reaction solution was analyzed by HPLC, and the yield was 95% and the enantiomeric excess was 0.7%.
カルボベンジルオキシ−α−Ｌ−アスパルチルーＬ−フ
ェニルアラニンメチルエステルのラセミ化、即ちα−Ｌ
−アスパルチルーＤ−フェニルアラニンメチルエステル
の生成はＨＰＬＣによる分析で１％以下であった。Racemization of carbobenzyloxy-α-L-aspartyl-L-phenylalanine methyl ester, i.e. α-L
The production of -aspartyl-D-phenylalanine methyl ester was determined to be less than 1% by HPLC analysis.
実施例 ３
実施例２と同様のメチルイソブチルケトン溶液を加圧下
、１１５℃に加熱、７０分間反応させた。Example 3 The same methyl isobutyl ketone solution as in Example 2 was heated to 115° C. under pressure and reacted for 70 minutes.
反応終了後、反応液中のフェニルアラニンメチルエステ
ルをＨＰＬＣで分析したところ、収率９２％、エナンチ
オマー過剰率３．６％であった。After the reaction was completed, HPLC analysis of phenylalanine methyl ester in the reaction solution revealed that the yield was 92% and the enantiomeric excess was 3.6%.
カルボベンジルオキシ−α−Ｌ−アスパルチル−し一フ
ェニルアラニンメチルエステルのラセミ化、即ちα−Ｌ
−アスパルチルーＤ−フェニルアラニン２メチルエステ
ルの生成はＨＰＬＣによる分析で１％以下であった。Racemization of carbobenzyloxy-α-L-aspartyl-monophenylalanine methyl ester, i.e. α-L
The production of -aspartyl-D-phenylalanine 2 methyl ester was determined to be less than 1% by HPLC analysis.
（発明の効果）
本発明の方法によれば、極めて効率よくペプチド類と共
存する光学活性アミノ酸を選択的にラセミ化することが
できる。しかもその際ペプチド合成の生成物などをほと
んどラセミ化しないとゆう優れた効果を奏する。(Effects of the Invention) According to the method of the present invention, optically active amino acids coexisting with peptides can be selectively racemized extremely efficiently. Furthermore, excellent effects can be achieved if the peptide synthesis products are hardly racemized.
Claims (1)
ド又はその誘導体の存在下で選択的にラセミ化すること
を特徴とする光学活性α−アミノ酸エステルのラセミ化
方法。 ２）ペプチド又はその誘導体として、Ｎ−ベンジルオキ
シカルボニル−Ｌ−アスパルチル−Ｌ−フェニルアラニ
ン又はその脂肪族低級アルキルエステルを用いる特許請
求の範囲第１項記載の方法。 ３）ラセミ化反応を６０℃ないし２００℃の温度範囲内
で行う特許請求の範囲第１項又は第２項記載の方法。 ４）極性溶媒としてケトンを用いる特許請求の範囲第１
項ないし第３項のいずれかの項記載の方法。[Scope of Claims] 1) A method for racemizing an optically active α-amino acid ester, which comprises selectively racemizing an optically active α-amino acid ester in the presence of a peptide or a derivative thereof in a polar solvent. 2) The method according to claim 1, wherein N-benzyloxycarbonyl-L-aspartyl-L-phenylalanine or an aliphatic lower alkyl ester thereof is used as the peptide or its derivative. 3) The method according to claim 1 or 2, wherein the racemization reaction is carried out within a temperature range of 60°C to 200°C. 4) Claim 1 using a ketone as a polar solvent
The method described in any of paragraphs 3 to 3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP32286387A JPH01165559A (en) | 1987-12-22 | 1987-12-22 | Selective racemization of optically active amino acid ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP32286387A JPH01165559A (en) | 1987-12-22 | 1987-12-22 | Selective racemization of optically active amino acid ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01165559A true JPH01165559A (en) | 1989-06-29 |
Family
ID=18148450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP32286387A Pending JPH01165559A (en) | 1987-12-22 | 1987-12-22 | Selective racemization of optically active amino acid ester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01165559A (en) |
-
1987
- 1987-12-22 JP JP32286387A patent/JPH01165559A/en active Pending
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