Total synthesis of cystothiazoles A and C.
An efficient pathway culminating in the enantiocontrolled preparation of cystothiazoles A and C has been described. The cystothiazoles demonstrate potent antifungal activity and function as novel inhibitors of mitochondrial oxidation 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 synthesis of a variety of related five-membered heterocyclic systems and for biological investigations of structure-activity relationships. The core [2,4']bisthiazole component 8 was prepared in six steps, and the use of the Horner-Emmons olefination to yield the alpha,beta-unsaturated ester 10 set the stage for an asymmetric Evans aldol process, which established the required C(4)/C(5) stereochemistry. Finally the cystothiazoles A and C were prepared via a stereocontrolled O-alkylation of the precursor beta-keto esters 22a and 22b.
Williams
D R
DR
Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA. williamd@indiana.edu
Patnaik
S
S
Clark
M P
MP
D020564:Deltaproteobacteria / Q000737:chemistry; D005659:Fungicides, Industrial / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis*
D005659:Fungicides, Industrial; D007202:Indicators and Reagents; D013844:Thiazoles; C112182:cystothiazole A; C443723:cystothiazole C