Enantiopure Synthesis of Side Chain-Modified α-Amino Acids and 5-cis-Alkylprolines

Abstract

A short, concise synthesis of enantiopure, side chain-modified α-amino acids such as 4-oxo-l-norvaline, 6-oxo-l-homonorleucine, and 5-cis-alkyl prolines is described. Knoevenagel condensation of l-aminocarboxylate-derived β-ketoesters with aldehydes followed by reductive decarboxylation results in unnatural α-amino acids in good yield. A fluorescent amino acid is synthesized using a similar protocol. These studies show that aminocarboxylate-derived β-ketoesters are very useful intermediates and the method employed is both general and practical for the preparation of γ(δ)-oxo α-amino acids and alkylprolines.