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), BocGlyIleValGlu(OBu t )Gln Ser(Bu t )LeuOH ( 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), HCys(Trt)Cys(Acm)Thr(Bu t )Ser(Bu t )IleCys(Trt)Ser(Bu t )LeuOH ( 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.