Stereochemically defined C-substituted glutamic acids and their derivatives. 1. An efficient asymmetric synthesis of (2S,3S)-3-methyl- and - 3-trifluoromethylpyroglutamic acids

Vadim A. Soloshonok, Chaozhong Cai, Victor J. Hruby, Luc Van Meervelt, Nikolai Mischenko

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

An efficient asymmetric synthesis of biologically important (2S,3S)-3- methyl- and (2S,3S)-3-trifluoromethylpyroglutamic acid has been developed. The method consists of diastereoselective Michael addition reaction between ethyl crotonate or ethyl 4,4,4-trifluorocrotonate and a Ni(II) complex of the chiral non-racemic Schiff base of glycine with (S)-o-[N-(N- benzylprolyl)amino]benzophenone (BPB) followed by decomposition of the addition products by aq. HCl and treatment of the resultant glutamic acid derivatives with NH4OH to afford the target pyroglutamic acids along with recovery of the chiral auxiliary BPB. The stereochemical outcome of the addition reactions was found to be subjected to kinetic control. A mechanistic rationale for the observed stereochemical preferences is discussed.

Original languageEnglish (US)
Pages (from-to)12031-12044
Number of pages14
JournalTetrahedron
Volume55
Issue number41
DOIs
StatePublished - Oct 8 1999

Keywords

  • Addition reactions
  • Amino acids and derivatives
  • Asymmetric synthesis
  • Mechanism
  • Nickel

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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