Efficient synthesis of enantiomerically pure beta2-amino acids via chiral isoxazolidinones

J Org Chem. 2003 Feb 21;68(4):1575-8. doi: 10.1021/jo026738b.

Abstract

We report a practical and scalable synthetic route for the preparation of alpha-substituted beta-amino acids (beta(2)-amino acids). Michael addition of a chiral hydroxylamine, derived from alpha-methylbenzylamine, to an alpha-alkylacrylate followed by cyclization gives a diastereomeric mixture of alpha-substituted isoxazolidinones. These diastereomers are separable by column chromatography. Subsequent hydrogenation of the purified isoxazolidinones followed by Fmoc protection affords enantiomerically pure Fmoc-beta(2)-amino acids, which are useful for beta-peptide synthesis. This route provides access to both enantiomers of a protected beta(2)-amino acid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / chemical synthesis*
  • Catalysis
  • Combinatorial Chemistry Techniques
  • Isoxazoles / chemistry*
  • Molecular Structure
  • Stereoisomerism

Substances

  • Amino Acids
  • Isoxazoles