Synthesis and evaluation of enantiomeric purity of protected alpha-amino and peptide aldehydes

The synthesis of enantiomerically pure Ac-Tyr-Val-Ala-Asp(O'Bu)-H dimethyl acetal ((S)-1) is reported, a protected tetrapeptide C-terminal aldehyde be longing to a class of potent, reversible inhibitors of cysteine proteases ( e.g.. interleukin-1 beta-converting enzyme (ICE), also called caspase-1). T he coupling of the precursors Ac-Tyr-Val-Ala-OH ((S)-8) and H-Asp(O'Bu)-H d imethyl acetal ((S)-6) gave (S)-1 in a yield of 85%, with epimerization of < 2% at the alanine and aspartic-acid residue. (S)-6 itself was synthesized in four steps in an overall yield of 83% with an ee >98%.