Synthesis of tyrocidine A and its analogues by spontaneous cyclization in aqueous solution.
[reaction: see text] Head-to-tail cyclization of peptides is a multistep process involving tedious C-terminal activation and side chain protection. Here we report a facile, quantitative cyclization method in aqueous ammonia solution for the total syntheses of the cyclic decapeptide antibiotic Tyrocidine A and its analogues from their fully deprotected linear thioester precursors on a solid support. This novel aqueous method is conformation-dependent and may be applicable to syntheses of other natural cyclic peptides.
Department of Chemistry and Biotechnology Research Institute, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Xianzhang
X
Bu
Xiaoming
X
Wu
Guiyang
G
Xie
Zhihong
Z
Guo
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D003500:Cyclization; D010456:Peptides, Cyclic / Q000138:chemical synthesis; D012996:Solutions; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014440:Tyrocidine / Q000138:chemical synthesis*
D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic; D012996:Solutions; D013438:Sulfhydryl Compounds; D014440:Tyrocidine