Realization of the synthesis of α,α-disubstituted carbamylacetates and cyanoacetates by either enzymatic or chemical functional group transformation, depending upon the substrate specificity of Rhodococcus amidase

Masahiro Yokoyama, Mieko Kashiwagi, Masakazu Iwasaki, Ken Ichi Fuhshuku, Hiromichi Ohta, Takeshi Sugai

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Substrate specificity and enantioselectivity of nitrile hydratase and amidase from R. rhodochrous IFO 15564 has been studied by applying a series of α,α-disubstituted malononitriles and related substrates. The amidase preferentially hydrolyzed the pro-(R) carbamyl group (amide) of the prochiral diamides, an intermediate resulting from the action of nitrile hydratase in a non-enantiotopic group-selective manner. The introduction of a fluorine atom at the α-position caused an inhibitory effect on amidase. By a combination of this microbial transformation and the subsequent Hofmann rearrangement, an important precursor of (S)-methyldopa with 98.4% ee has been prepared. For the enzymatically poor substrate, the action on HO3SONO-H2O on the carbamyl group was effective, leaving the cyano group intact. This conversion is demonstrated as the key step for the expeditious preparation of (±)-α-cyano-α-fluoro-α-phenylacetic acid (CFPA) from diethyl α-fluoro-α-phenylmalonate.

Original languageEnglish
Pages (from-to)2817-2820
Number of pages4
JournalTetrahedron Asymmetry
Volume15
Issue number18
DOIs
Publication statusPublished - 2004 Sep 20

ASJC Scopus subject areas

  • Catalysis
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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