Synthesis of Nα‐Fmoc protected derivatives of S‐(2,3‐dihydroxypropyl)‐cysteine and their application in peptide synthesis

Acylated derivatives of S ‐(2,3‐dihydroxypropyl)‐cysteine ( S ‐glycerylcysteine) form the N ‐terminus of structural and functional proteins of bacterial origin. Synthetic lipopeptides containing tripalmitoyl‐ S ‐glycerylcysteine are derived from bacterial lipoprotein and constitute potent immunoadjuvants activating both B‐lymphocytes and macrophages. There is increasingly interest in conjugates consisting of tripalmitoyl‐ S ‐glycerylcysteine linked to appropriate viral and bacterial antigens, because of their capability of inducing antigen specific antibodies and T‐helper and T‐killer cell specific immune responses. A new convenient synthetic pathway for the preparation of these tripalmitoyl‐ S ‐glycerylcysteinyl peptides is described. The use of N α ‐Fmoc‐protected S ‐(2,3‐dihydroxypropyl)‐cysteine and its O,O′ ‐bis acylated derivatives for the synthesis of triacyl‐ S ‐glycerylcysteinyl, O,O ′‐bis‐acyl‐5‐glycerylcysteinyl and S ‐glycerylcysteinyl peptides of high diastereomeric purity by solid phase peptide synthesis or synthesis in solution is demonstrated.