Use of enzyme penicillin acylase in selective amidation/amide hydrolysis to resolve ethyl 3-amino-4-pentynoate isomers

被引:38
作者
Topgi, RS
Ng, JS
Landis, B
Wang, P
Behling, JR
机构
[1] SEARLE, Chem Sci, R&D, Skokie, IL 60077 USA
[2] Monsanto Co, Bioproc Grp, St Louis, MO 63198 USA
关键词
penicillin acylase; resolve; beta-amino acid; acylation; deacylation;
D O I
10.1016/S0968-0896(99)00155-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The beta-amino acid, (S)-ethyl-3-amino-4-pentynoate: is a chiral synthon used in the synthesis of xemilofiban hydrochloride, an anti-platelet agent. A biocatalytic approach was developed to resolve (R)- and (S)-enantiomers of ethyl 3-amino-4-pentynoate in enantiomerically pure form employing the enzyme Penicillin acylase. In the acylation, phenylacetic acid was used as an acylating agent. We have shown that both the acylation and deacylation can be employed and that the activity of the enzyme Penicillin acylase can be controlled by maintaining an appropriate pH of the reaction medium. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:2221 / 2229
页数:9
相关论文
共 61 条
  • [1] LEWIS ACID-PROMOTED 1,4-ADDITION TO CHIRAL IMIDE DERIVATIVES IN THE SYNTHESIS OF BETA-AMINO ACIDS
    AMOROSO, R
    CARDILLO, G
    SABATINO, P
    TOMASINI, C
    TRERE, A
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (21) : 5615 - 5619
  • [2] ENZYMATIC CONVERSION IN AQUEOUS TWO-PHASE SYSTEMS: DEACYLATION OF BENZYLPENICILLIN TO 6-AMINOPENICILLANIC ACID WITH PENICILLIN ACYLASE.
    Andersson, Elis
    Mattiasson, Bo
    Hahn-Hagerdal, Barbel
    [J]. Enzyme and Microbial Technology, 1984, 6 (07) : 301 - 306
  • [3] BABIAK K, 1996, Patent No. 5536869
  • [4] PHENYLACETYLOXYMETHYLENE, A CARBOXYL PROTECTING GROUP REMOVABLE WITH IMMOBILIZED PENICILLIN ACYLASE, USEFUL IN BENZYL PENICILLIN CHEMISTRY
    BALDARO, E
    FAIARDI, D
    FUGANTI, C
    GRASSELLI, P
    LAZZARINI, A
    [J]. TETRAHEDRON LETTERS, 1988, 29 (36) : 4623 - 4624
  • [5] PEN-G ACYLASE CATALYZED RESOLUTION OF PHENYLACETATE ESTERS OF SECONDARY ALCOHOLS
    BALDARO, E
    DARRIGO, P
    PEDROCCHIFANTONI, G
    ROSELL, CM
    SERVI, S
    TAGLIANI, A
    TERRENI, M
    [J]. TETRAHEDRON-ASYMMETRY, 1993, 4 (05) : 1031 - 1034
  • [6] A synthesis of the platelet aggregation inhibitor xemilofiban from L-aspartic acid. Confirmation of the absolute configuration.
    Boys, ML
    [J]. TETRAHEDRON LETTERS, 1998, 39 (21) : 3449 - 3450
  • [7] AN EXPEDITIOUS ASYMMETRIC-SYNTHESIS OF ALLOPHENYLNORSTATINE
    BUNNAGE, ME
    DAVIES, SG
    GOODWIN, CJ
    ICHIHARA, O
    [J]. TETRAHEDRON, 1994, 50 (13) : 3975 - 3986
  • [8] ASYMMETRIC SYNTHESES OF OPTICALLY-ACTIVE ALPHA,BETA-DISUBSTITUTED BETA-AMINO ACIDS
    BURGESS, K
    LIU, LT
    PAL, B
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (17) : 4758 - 4763
  • [9] Cardillo G, 1999, EUR J ORG CHEM, V1999, P155
  • [10] Enzymatic resolution of alpha-alkyl beta-amino acids using immobilized penicillin G acylase
    Cardillo, G
    Tolomelli, A
    Tomasini, C
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (24) : 8651 - 8654