PREPARATION OF A PROTECTED (2S,3S)-BETA-HYDROXYASPARTIC ACID SUITABLE FOR SOLID-PHASE PEPTIDE-SYNTHESIS

(2S,3S)-N-Boc-3-(benzyloxy)aspartic acid beta-benzyl ester (2), a beta-hydroxyaspartic acid derivative suitably protected for incorporation into peptides by solid-phase synthesis, was synthesized from N-Boc-(R)-serine via the intermediate, [4R-(R*,R*)]-4-[hydroxy[2-(trimethylsilyl)ethynyl]methyl]-2,2-dimethyl-3-oxazolidinecarboxylic acid 1,1-dimethylethyl ester (5). Key transformations involved the ruthenium tetraoxide mediated oxidation of the ethynyl moiety to form the beta-carboxylic acid and, after esterification and oxazolidine ring hydrolysis, dichromate oxidation of the resulting primary alcohol to the alpha-carboxylic acid. The method is suitable for the preparation of gram quantities of 2.