title: Cysteinoyl- and cysteine-containing dipeptidoylbenzotriazoles with free sulfhydryl groups: easy access to N-terminal and internal cysteine peptides.
abstract: 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.
authors.affiliation: Department of Chemistry, Center for Heterocyclic Compounds, University of Florida, Gainesville, FL 32611-7200, USA.
authors.forename: Tarek S
authors.initials: TS
authors.lastname: Ibrahim
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Tala
authors.forename: Said A
authors.initials: SA
authors.lastname: El-Feky
authors.forename: Zakaria K
authors.initials: ZK
authors.lastname: Abdel-Samii
authors.forename: Alan R
authors.initials: AR
authors.lastname: Katritzky
mesh_terms: D000215:Acylation; D000595:Amino Acid Sequence; D003545:Cysteine / Q000138:chemical synthesis / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D013438:Sulfhydryl Compounds; D014230:Triazoles; C012771:benzotriazole; D003545:Cysteine