5-aminooxazole as an internal traceless activator of C-terminal carboxylic acid:: Rapid access to diversely functionalized cyclodepsipeptides

被引:26
作者
Bughin, C
Zhao, G
Bienaymé, H
Zhu, JP [1 ]
机构
[1] CNRS, Inst Chim Subst Nat, F-91198 Gif Sur Yvette, France
[2] Pierre Fabre Urol, F-69100 Villeurbanne, France
关键词
cyclization; domino reactions; macrocycles; multicomponent reactions; peptides;
D O I
10.1002/chem.200500703
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A conceptually novel macrolactonization protocol has been developed. It is a domino process involving a sequence of: 1) protonation of 5-aminooxazole leading to the electrophilic iminium salt; 2) trapping of the iminium species by the neighboring C-terminal carboxylic acid leading to a putative spirolactone; and 3) intramolecular nucleophilic addition of the tethered alcohol to the spirolactone followed by fragmentation. The strategically incorporated 5-aminooxazole serves as an internal traceless activator of the neighboring C-terminal carboxylic acid, since it became an integral part of the peptide backbone after cyclization. No coupling reagent is required and the entire sequence is triggered by just a few equivalents of trifluoroacetic acid under very mild conditions (MeCN as the solvent at room temperature). The spirolactone as an activated form of the carboxylic acid has been evidenced by a sulfur-migration experiment. By combining with a three-component synthesis of 5-aminooxazole, a two-step synthesis of structurally complex cyclodepsipeptides from readily accessible starting materials was developed.
引用
收藏
页码:1174 / 1184
页数:11
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