Solid phase library synthesis of cyclic depsipeptides: Aurilide and aurilide analogues

Takashi Takahashi, Hiroyuki Nagamiya, Takayuki Doi, Peter G. Griffiths, Andrew M. Bray

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

A solid-phase combinatorial synthesis approach toward the cyclic depsipeptide aurilide (1) and related analogues is described. The peptide moiety 2 was assembled on trityl linker-functionalized SynPhase Crowns using an Fmoc strategy. Optimization of the tetrapeptide assembly 5 was carried out using parallel multiple synthesis and LC/MS analysis. The aliphatic moiety 3a was coupled with the solid-supported 2 using DIC/HOBt. Following deprotection and cleavage of linear precursor 26, macrocyclization was achieved under high dilution conditions. Removal of the methylthiomethyl protecting group provided aurilide (1) in 11% overall yield. Synthesis of a combinatorial library of aurilide derivatives 4 was accomplished with a similar protocol using the TranSort technique.

Original languageEnglish
Pages (from-to)414-428
Number of pages15
JournalJournal of Combinatorial Chemistry
Volume5
Issue number4
DOIs
Publication statusPublished - 2003 Jul 1
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)

Fingerprint Dive into the research topics of 'Solid phase library synthesis of cyclic depsipeptides: Aurilide and aurilide analogues'. Together they form a unique fingerprint.

Cite this