Peptides by Extension at the N- or C-terminii of Lysine

Dipeptides 3a–g, (3a + 3a′), (3d + 3d′), (3l + 3l′)a and tripeptides 6a–e, (6b + 6b′), (6e + 6e′) incorporating Zε‐Lys were prepared in high yields (70–95%) and enantiopurity (≥97%) in partially aqueous acetonitrile solution by coupling using (i) Zε‐Lys with N‐(Z‐ and Fmoc‐aminoacyl)benzotriazoles 1a–g, (ii) Zε‐Lys with N‐Z‐dipeptidoylbenzotriazoles 5a–c, and (iii) N‐Fmocα‐Zε‐l‐Lys‐Bt 1h and amino acids 2a,c–e. Unnatural dipeptides 3h–j, (3h + 3h′) and tripeptides 6f were similarly prepared from Zα‐Lys. Retention of chirality was demonstrated by parallel experiments involving l‐Ala, dl‐Ala, l‐Met, and dl‐Met by NMR and HPLC analysis.