Multicomponent Synthesis of Cyclic Depsipeptide Mimics by Ugi Reaction Including Cyclic Hemiacetals Derived from Asymmetric Organocatalysis

Multicomponent Synthesis of Cyclic Depsipeptide Mimics by Ugi Reaction Including Cyclic Hemiacetals Derived from Asymmetric Organocatalysis

de la Torre,A. F.; Rivera, D. G.; Concepción, O.; Echemendia, R.; Correa, A. G. ; Paixão, M. W. J. Org. Chem., 2016, 81, 803–809. DOI: 10.1021/acs.joc.5b02158

The synthesis of novel cyclic depsipeptide mimics by means of an organocatalytic conjugate addition, leading to chiral cyclic hemiacetals, followed by a multicomponent reaction with α-amino acids and isocyanides, is described. The initial organocatalytic step is employed for the asymmetric derivatization of α,β-unsaturated aldehydes to 4,5-disubstituted 2-hydroxytetrahydropyrans, which are next used as chiral bifunctional substrates on the Ugi five-center three-component reaction, giving rise to nine-membered-ring lactones.