Advanced asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by alkylation/cyclization of newly designed axially chiral Ni(II) complex of glycine Schiff base

Amino Acids. 2016 Apr;48(4):973-986. doi: 10.1007/s00726-015-2138-3. Epub 2015 Dec 11.

Abstract

Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is in extremely high demand due to the pharmaceutical importance of this tailor-made, sterically constrained α-amino acid. Here we report the development of an advanced procedure for preparation of the target amino acid via two-step SN2 and SN2' alkylation of novel axially chiral nucleophilic glycine equivalent. Excellent yields and diastereoselectivity coupled with reliable and easy scalability render this method of immediate use for practical synthesis of (1R,2S)-vinyl-ACCA.

Keywords: Amino acids; Anti-viral (HCV) activity; Asymmetric synthesis; Chirality; Schiff bases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Antiviral Agents / chemical synthesis*
  • Catalysis
  • Cations, Divalent
  • Coordination Complexes / chemical synthesis*
  • Cyclization
  • Cyclopropanes / chemical synthesis*
  • Glycine / chemistry*
  • Molecular Structure
  • Nickel / chemistry*
  • Schiff Bases / chemistry*
  • Stereoisomerism
  • Vinyl Compounds / chemical synthesis*

Substances

  • (1R,2S)-1-amino- 2-vinylcyclopropanecarboxylic acid
  • Antiviral Agents
  • Cations, Divalent
  • Coordination Complexes
  • Cyclopropanes
  • Schiff Bases
  • Vinyl Compounds
  • Nickel
  • Glycine