Synthese von Humaninsulin. II. Aufbau des cyclischen Fragments A(1–13)

Synthesis of human insulin. II. Preparation of the A(1–13) fragment. The present report gives a detailed account of the synthesis of the protected tridecapeptide A(1–13), BocGlyIleValGlu(OBut)Gln Ser(But)LeuOH (20), an essential intermediate in the recently published total synthesis of human insulin [1]. The main feature in the synthesis of 20 was the specific formation of a disulfide bond between A6 and A11 in the presence of an additional cysteine residue (A7). The selective ring closure was accomplished with the segment A(6–13), HCys(Trt)Cys(Acm)Thr(But)Ser(But)IleCys(Trt)Ser(But)LeuOH (18), which was obtained by way of conventional synthesis routes. Treatment of 18 with iodine in trifluoroethanol formed the desired disulfide bridge from the two S‐trityl‐cysteine residues without affecting the S‐acetamidomethyl‐protected cysteine A7. A final azide coupling with the N‐terminal derivative A(1–5) (3) provided the tridecapeptide fragment 20 as a crystalline compound.