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Synthese von Humaninsulin. II. Aufbau des cyclischen Fragments A(1–13)
Author(s) -
Sieber Peter,
Kamber Bruno,
Eisler Karel,
Hartmann Albert,
Riniker Bernhard,
Rittel Werner
Publication year - 1976
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19760590510
Subject(s) - chemistry , stereochemistry , disulfide bond , cysteine , human insulin , residue (chemistry) , azide , derivative (finance) , insulin , biochemistry , organic chemistry , enzyme , medicine , financial economics , economics , endocrinology
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.