A convenient synthesis of human calcitonin mainly via the repetitive excess mixed anhydride method

Abstract

AbstractThe synthesis is described of the sequence containing 32 amino acid residues proposed for human calcitonin (HCT), presumably a thyroid hormone (Fig. 1)4.Our strategy employed the coupling of four fragments: 1–7 (with closed disulfide bridge), 8‐10, 11‐19 and 20‐32 via the azide or dicyclohexylcarbodiimide (DCCI) method. With the exception of two DCCI couplings (Asn3 and Asn17), these fragments were prepared exclusively by stepwise synthesis via the repetitive excess mixed anhydride (REMA) méthod (Fig. 2).Removal in one operation of all protecting groups with cold concentrated hydrochloric acid and chromatographic purification afforded HCT with full hypocalcemic potency (Table 1).