title: HBTU mediated 1-hydroxybenzotriazole (HOBt) conjugate addition: synthesis and stereochemical analysis of β-benzotriazole N-oxide substituted γ-amino acids and hybrid peptides.
abstract: HBTU is a standard coupling agent commonly used for the activation of free carboxylic acids during the solution and solid phase peptide synthesis. 1-Hydroxybenzotriazole (HOBt) plays a significant role in reducing the racemization during peptide synthesis; hence it is regularly used as a coupling additive. Here, we are reporting the mild and facile conjugate addition of HOBt to E-vinylogous γ-amino acids mediated by the HBTU. The reaction is moderately diastereoselective and novel β-benzotriazole N-oxide (β-BtO) substituted γ-amino acids were isolated in moderate to good yields. The single crystal analysis of methyl esters of major (anti) and minor (syn) conjugate addition products infers the formation of exclusively N-alkylated benzotriazole N-oxides instead of O-alkylation of HOBt. In addition, we showed the utilization of β-BtO substituted γ-amino acids in peptide synthesis and studied their conformations in single crystals.
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pune-411 008, India. hn.gopi@iiserpune.ac.in.
authors.forename: Sachitanand M
authors.initials: SM
authors.lastname: Mali
authors.forename: Mothukuri
authors.initials: M
authors.lastname: Ganesh Kumar
authors.forename: Mona M
authors.initials: MM
authors.lastname: Katariya
authors.forename: Hosahudya N
authors.initials: HN
authors.lastname: Gopi
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002234:Carbodiimides / Q000737:chemistry; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010087:Oxides / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D002234:Carbodiimides; D010087:Oxides; D010455:Peptides; D014230:Triazoles; C012771:benzotriazole; C011852:1-hydroxybenzotriazole