Solid phase library synthesis of cyclic depsipeptides: aurilide and aurilide analogues.
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.
Takahashi
Takashi
T
Department of Applied Chemistry, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan. ttakashi@o.cc.titech.ac.jp
Nagamiya
Hiroyuki
H
Doi
Takayuki
T
Griffiths
Peter G
PG
Bray
Andrew M
AM
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D019151:Peptide Library; D010456:Peptides, Cyclic