Asymmetric total synthesis of (+)-carbocyclic uracil polyoxin C

Abstract

A short, practical, asymmetric synthesis of carbocyclic uracil polyoxin C is described. The key step in the synthesis is a regio- and stereo-selective palladium-mediated substitution reaction of an α-amino substituted unsaturated lactone with bis-silylated uracil. Critical to the success of this reaction is the use of trimethylsilyl chloride in the reaction mixture which substantially enhances the reactivity of the lactone. The final stages involve dihydroxylation of 1,4-disubstituted cyclopentene which is essentially non-selective. The factors surrounding the poor selectivity of this reaction are discussed.