Title:
SYNTHESIS OF CHIRAL INTERMEDIATES USEFUL IN PREPARING PHARMACOLOGICALLY ACTIVE COMPOUNDS
Document Type and Number:
WIPO Patent Application WO2002042244
Kind Code:
A3
Abstract:
A process is disclosed for preparing (R)-2-hydroxy-4-phenylbutyronitrile of formula (I) wherein * signifies the (R) stereoisomer; and Ph is the phenyl group C6H5, which process comprises reacting, in a biphasic system, 3-phenylpropionaldehyde of formula (X): with a cyanide compound in the presence of (R)-hydroxynitrilase, wherein the reaction is carried out a temperature below (10) DEG C. Preferably, the reaction is carried out at a temperature in the range of from -(5) DEG to (0) DEG C. The compounds of formula (I) thereby prepared are useful in the preparation of the family of ACE inhibitors known as 'prils', of the general formula (A): wherein R' is hydrogen or C1-C2 alkyl and R'' is selected from a large number of possible moieties. Example of "prils" include lisinopril, cilazapril, enalapril, benazepril, ramipril, delapril, enalaprilat, imidapril, spirapril, trandolapril and others. These 'prils' compounds are chiral compounds, only one of their diastereomers being pharmacologically active. Use of a chiral intermediate (I) thereby avoids the necessity to isolate and purify the active 'pril' diastereomer, rather than using a racemic mixture, for pharmaceutical/medical applications.
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Inventors:
TIKARE RAVEENDRA KHANDURAO (IN)
Application Number:
PCT/IB2001/002794
Publication Date:
August 15, 2002
Filing Date:
November 21, 2001
Export Citation:
Assignee:
FERMENTA BIOTECH LTD (IN)
TIKARE RAVEENDRA KHANDURAO (IN)
TIKARE RAVEENDRA KHANDURAO (IN)
International Classes:
C07C253/00; C07C255/36; C07D207/16; C07D209/02; C07D209/42; C07D223/16; C07D233/38; C07D487/04; C07D495/10; C12N9/88; C12P13/00; C12P13/04; (IPC1-7): C12P13/00; C12P13/04; C12N9/88
Foreign References:
| EP0547655A1 | 1993-06-23 | |||
| US5552317A | 1996-09-03 |
Other References:
COSTES DAVID ET AL: "Hydroxynitrile lyase-catalyzed synthesis of cyanohydrins in organic solvents: Parameters influencing activity and enantiospecificity.", ENZYME AND MICROBIAL TECHNOLOGY, vol. 25, no. 3-5, August 1999 (1999-08-01), pages 384 - 391, XP002202117, ISSN: 0141-0229
PATENT ABSTRACTS OF JAPAN vol. 014, no. 543 (C - 0783) 30 November 1990 (1990-11-30)
LOOS W T ET AL: "SYNTHESIS OF OPTICALLY ACTIVE CYANOHYDRINS USING R-OXYNITRILASE IN A LIQUID-LIQUID BIPHASIC SYSTEM PART 1: AN INDUSTRIALLY USEFUL PROCEDURE", BIOCATALYSIS AND BIOTRANSFORMATION, HARWOOD ACADEMIC PUBL., BASEL, CH, vol. 12, 1995, pages 255 - 266, XP001021485, ISSN: 1024-2422
PATENT ABSTRACTS OF JAPAN vol. 014, no. 543 (C - 0783) 30 November 1990 (1990-11-30)
LOOS W T ET AL: "SYNTHESIS OF OPTICALLY ACTIVE CYANOHYDRINS USING R-OXYNITRILASE IN A LIQUID-LIQUID BIPHASIC SYSTEM PART 1: AN INDUSTRIALLY USEFUL PROCEDURE", BIOCATALYSIS AND BIOTRANSFORMATION, HARWOOD ACADEMIC PUBL., BASEL, CH, vol. 12, 1995, pages 255 - 266, XP001021485, ISSN: 1024-2422
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