Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Patent
1998-08-26
1999-09-14
Barts, Samuel
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
544390, C07D24104
Patent
active
059525037
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to an industrial method for producing optically-active 2-piperazinecarboxylic acid derivatives which are useful as intermediate materials for drugs.
BACKGROUND ART
For producing optically-active 2-piperazinecarboxylic acid derivatives, for example, known are 1) a method of optical resolution using L-pyroglutamic acid as the resolving reagent (WO 95-21162), 2) a method of optical resolution using an optically-active .alpha.-hydroxy acid such as L-malic acid or the like as the resolving reagent (WO 95-29170), 3) a method of optical resolution using N-tosyl-L-phenylalanine as the resolving reagent (EP 710652), etc. However, as their solubility in water is high, the resolving reagents to be used in 1) and 2) are defective in that their recovery after use is low. On the other hand, as its solubility in acidic aqueous solutions is low, N-tolyl-L-phenylalanine to be used in 3) has the advantage of high recovery after use, but has the disadvantage of low production efficiency in that its ability to dissolve diastereomer salts is low and therefore the salt concentration in the resolving step using it could not be high, and that it requires expensive phenylalanine.
The present invention is to provide a method for producing optically-active 2-piperazinecarboxylic acid derivatives through diastereomer salt resolution, in which the recovery of the resolving reagent used is high and the production efficiency to give the products is high.
DISCLOSURE OF THE INVENTION
We, the present inventors have assiduously studied to obtain industrial methods for producing optically-active 2-piperazinecarboxylic acid derivatives, and, as a result, have found out that our object can be attained by using chemically-modified derivatives of inexpensive and easily-available, optically-active acidic amino acid derivatives as the resolving reagent for optically resolving 2-piperazinecarboxylic acid derivatives.
Specifically, the present invention is a method for producing optically-active 2-piperazinecarboxylic acid derivatives, which is characterized in that a 2-piperazinecarboxylic acid derivative is optically resolved with a resolving reagent of an optically-active acidic amino acid derivative such as an optically-active, N-acylated acidic amino acid derivative, an optically-active, N-sulfonylated acidic amino acid derivative or the like.
The resolving reagent, optically-active acidic amino acid derivative for use in the invention has 2 or more carboxyl groups and an amino group in the molecule, and includes, for example, optically-active, N-acylated acidic amino acid derivatives, optically-active, N-sulfonylated acidic amino acid derivatives, etc. Concretely, it may be selected from N-acylated derivatives and N-sulfonylated derivatives of optically-active aspartic acid and optically-active glutamic acid, and any of D-forms and L-forms of those derivatives may be used in accordance with the object.
As the optically-active N-acylated derivatives, usable are optically-active acidic amino acid derivatives of the following general formula (I): ##STR1## wherein R.sup.1 represents i) a hydrogen atom, ii) an unsubstituted or halogen-substituted, linear or branched alkyl group having from 1 to 10 carbon atoms, iii) an unsubstituted aryl group, or an aryl group substituted by an alkyl group having from 1 to 10 carbon atoms, an alkoxyl group having from 1 to 10 carbon atoms, a halogen atom or a hydroxyl group, iv) an aralkyl group of which the aromatic ring moiety is unsubstituted or substituted by an alkyl group having from 1 to 10 carbon atoms, an alkoxyl group having from 1 to 10 carbon atoms, a halogen atom or a hydroxyl group, or v) an aralkyloxy group of which the aromatic ring moiety is unsubstituted or substituted by an alkyl group having from 1 to 10 carbon atoms, an alkoxyl group having from 1 to 10 carbon atoms, a halogen atom or a hydroxyl group; and n represents 1 or 2. As their specific examples, mentioned are acetylaspartic acid, formylglutamic acid, isobutyroylaspartic acid, benzoy
REFERENCES:
patent: 5413999 (1995-05-01), Vacca et al.
Fujino Toshihiro
Sato Haruyo
Barts Samuel
Miller Austin R.
Toray Industries Inc.
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