Total synthesis of antitumor agent at-125, (α S,5 S)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid

Abstract

A short and efficient total synthesis of racemic AT-125 and its racemic threo isomer proceeds via an intramolecular Michael cyclization of a protected α,β-dehydroglutamic acid γ-hydroxamate. Separation of diastereomers and deprotection to racemic AT-125 followed by enzymatic resolution of the N-chloroacetamide with hog-kidney acylase provides the natural α S,5 S isomer.