Cysteine Isocyanide in Multicomponent Reaction: Synthesis of Peptido-Mimetic 1,3-Azoles

An alternative approach toward the
simple and robust synthesis
of highly substituted peptidic thiazole derivatives using Ugi-multicomponent
reaction (U-MCR) is described. Thus, we introduced the enantiopure
(R)-2-methyl-2-isocyano-3-(tritylthio)­propanoate
as a novel class of isocyanide in MCR. This bifunctional isocyanide
was found to undergo mild cyclodehydration to afford thiazole containing
peptidomimetics in a short synthetic sequence. Several examples of
bis-heterocyclic rings were also synthesized through the proper choice
of the aldehyde component in the U-4CR. The method opens a wide range
of applications toward the synthesis of nonribosomal natural products
and other bioactive compounds.