Synthesis of thioureido peptidomimetics employing alkyl azides and dithiocarbamates

Abstract

An unprecedented approach for the assembly of thioureido peptidomimetics is developed employing alkyl azides and dithiocarbamates. Dithiocarbamates react with alkyl azides with the liberation of N2 and elemental sulfur thereby leading to thiourea in a traceless manner. Thioureido peptidomimetics are thus furnished in good yields with no epimerization. This process is mild, free from the use of a base, scalable and step economic. The practicability of this methodology has been highlighted by the synthesis of N,N'-orthogonally protected thioureido peptidomimetics.

A Decade of Advances of CS2/Amines in Three-Component Reactions

“…The unique features of the azido group can make it function as electrophile. 26a The reaction 26b between dithiocarbamates 22.1 and alkyl azides liberates N 2 and elemental sulfur to yield thiourea 22.4 (Scheme 22 ). Dithiocarbamates 22.1 were prepared in situ from CS 2 and an amine in the presence of pyridine.…”