Total synthesis of cystothiazoles A and C

An efficient pathway culminating in the enantiocontrolled preparation of cy stothiazoles A and C has been described. The cystothiazoles demonstrate pot ent antifungal activity and function as novel inhibitors of mitochondrial o xidation at a specific site on the cytochrome bc(1) complex. These studies outline a general and flexible plan that can be readily adapted for the syn thesis of a variety of related five-membered heterocyclic systems and for b iological investigations of structure-activity relationships, The core [2,4 ']bisthiazole component 8 was prepared in six steps, and the use of the Hor ner-Emmons olefination to yield the alpha,beta -unsaturated ester 10 set th e stage for an asymmetric Evans aldol process, which established the requir ed C-4/C-5 stereochemistry. Finally the cystothiazoles A and C were prepare d via a stereocontrolled O-alkylation of the precursor beta -keto esters 22 a and 22b.