5-Aminooxazole as an internal traceless activator of C-terminal carboxylic acid: rapid access to diversely functionalized cyclodepsipeptides.
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.
Bughin
Carine
C
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France.
Zhao
Gang
G
Bienaymé
Hugues
H
Zhu
Jieping
J
D002264:Carboxylic Acids / Q000737:chemistry*; D003500:Cyclization; D047630:Depsipeptides / Q000138:chemical synthesis*; D010080:Oxazoles / Q000737:chemistry*; D013148:Spironolactone / Q000737:chemistry; D014269:Trifluoroacetic Acid / Q000737:chemistry
D002264:Carboxylic Acids; D047630:Depsipeptides; D010080:Oxazoles; D013148:Spironolactone; D014269:Trifluoroacetic Acid