Scholarlink

This chapter reports the successful synthesis of talarolide A (1), a natural product exhibiting a unique hydroxamate H-bond bridge, through a carefully designed solid-phase approach. By systematically selecting the disconnection site, we synthesized a protected linear precursor, which was then sequentially deprotected and cyclized. We discovered that the order of deprotection and cyclization was critical: precyclization of the unprotected peptide facilitated the correct conformational folding essential for achieving the natural product’s structure. This approach not only yielded talarolide A but also revealed a noncanonical atropisomer (atrop-talarolide A 5), providing new insights into the role of hydroxamate H-bond bridging in atropisomerism among nonribosomal peptide synthetase (NRPS)-derived cyclic peptides.

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Total Synthesis of N-hydroxy Cyclic Peptide: Talarolide A

  • 实验方案

  • 发表日期：

    2025年

查看全文
  • Waleed M. Hussein,
  • Yuxuan Zhu,
  • Angela A. Salim,
  • Robert J. Capon

摘要

This chapter reports the successful synthesis of talarolide A (1), a natural product exhibiting a unique hydroxamate H-bond bridge, through a carefully designed solid-phase approach. By systematically selecting the disconnection site, we synthesized a protected linear precursor, which was then sequentially deprotected and cyclized. We discovered that the order of deprotection and cyclization was critical: precyclization of the unprotected peptide facilitated the correct conformational folding essential for achieving the natural product’s structure. This approach not only yielded talarolide A but also revealed a noncanonical atropisomer (atrop-talarolide A 5), providing new insights into the role of hydroxamate H-bond bridging in atropisomerism among nonribosomal peptide synthetase (NRPS)-derived cyclic peptides.