Cysteinoyl‐ and Cysteine‐containing Dipeptidoylbenzotriazoles with Free Sulfhydryl Groups: Easy Access to N‐terminal and Internal Cysteine Peptides

N‐Protected cysteines 4a–c each with a free sulfhydryl group were prepared in 70–75% yields by treatment of l ‐cysteine with 1‐(benzyloxycarbonyl) benzotriazole (Cbz‐Bt) 1a , N ‐( tert ‐butyloxy‐carbonyl)benzotriazole (Boc‐Bt) 1b , and 1‐(9‐fluorenylmethoxy‐carbonyl)benzotriazole (Fmoc‐Bt) 1c , respectively. N‐Protected, free sulfhydryl cysteines 4a–c were then converted into the corresponding N‐protected, free sulfhydryl cysteinoylbenzotriazoles 7a–c (70–85%), which on treatment with diverse amino acids and dipeptides afforded the corresponding N ‐ protected, free sulfhydryl N‐terminal cysteine dipeptides 8a–e and tripeptides 8f–h in 73–80% yields. N‐Protected, free sulfhydryl cysteine‐containing dipeptides 9a , b were converted into the corresponding N‐protected, free sulfhydryl dipeptidoylbenzotriazoles 10a , b (69–81%), which on treatment with amino acids, dipeptides, and a tripeptide afforded internal cysteine tripeptides 11a–c , tetrapeptides 11d , e and pentapeptide 11f , each containing a N ‐ protected, free sulfhydryl groups in 70–90% yields under mild conditions. Treatment of N‐protected, free sulfhydryl cysteinoylbenzotriazole 7a with diamines 12a , b afforded directly the cysteine‐containing disulfide‐bridged cyclic peptides 14a , b in 50% yields.