Asymmetric hydrolysis of prochiral dimethyl 3-benzyloxycarbonylaminoglutarate with microorganisms. Preparation of (S)-3-amino-4-methoxycarbonylbutyric acid for the synthesis of carbapenem and negamycin antibiotics.
Year: 1983
Type: article
Abstract: During the synthetic study of chiral compounds with biological significance using the chemicoenzymatic approach,1>2) we found that pig liver esterase hydrolyzed the pro-2?ester of dimethyl 3-benzyloxycarbonylaminoglutarate (1) to yield the half ester 2 with an Sconfiguration.This chiral half ester 2 was used as a versatile starting material for synthesis of the carbapenem and negamycin antibiotics by the chemical transformation shown in Scheme 1.2) However, enzymes from mammalian organs such as pig liver esterase are considered to be of limited use, expensive and impractical3~5) for the large scale production of such chiral compounds.With these problems in mind, we have looked for enzymes of a microbial origin which hydrolyze 1 more efficiently and morestereoselectively.Thus, about 500 species of microorganisms, including molds, yeasts, bacteria and actinomycetes were screened, and several bacteria, yeasts and actinomycetes were found to hydrolyze the prochiral diester 1 stereoselectively affording 2 with varying degrees of optical purity.It was shown that microorganisms which hydrolyzed 1 were
Authors: Hirokazu KOTANI, Yukari KUZE, Satoko UCHIDA, Toshinori MIYABE, Takamasa IIMORI, Kazuo OKANO, Susumu KOBAYASHI, Masaji OHNO
Institutions: Takara Shuzo Co., Ltd. (Japan), The University of Tokyo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W1998556863