Synthesis of the Pyridine Core of Cyclothiazomycin

Abstract

A highly convergent synthesis of the pyridine core of the thiopeptide antibiotic cyclothiazomycin has been developed based on a [2+2+2] cyclotrimerization key step. The regioselective assembly of the heterocyclic center of this important class of antibiotics takes advantage of a temporary silicon tether and the ruthenium-catalyzed cyclotrimerization reaction of a diyne and an electron-poor thiazole nitrile.