Efficient synthesis of enantiomerically pure beta2-amino acids via chiral isoxazolidinones.
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.
Lee
Hee-Seung
HS
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706-1396, USA.
Park
Jin-Seong
JS
Kim
Byeong Moon
BM
Gellman
Samuel H
SH
D000596:Amino Acids / Q000138:chemical synthesis*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D007555:Isoxazoles / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000596:Amino Acids; D007555:Isoxazoles