Concise syntheses of cystothiazoles A, C, D, and melithiazol B.

ABSTRACT

A convergent synthesis of cystothiazoles C 1 and D 3 was achieved based on Julia coupling between the functionalized aldehyde 5b, corresponding to left half of the final molecule, and aryl sulfone 6 or 7, bearing a bithiazole moiety, corresponding to right half. Methylation of 1 and 3 gave cystothiazole A 2 and melithiazol B 4, respectively. The overall yield (5 steps from (2R,3S)-3-methylpent-4-yne-1,2-diol 10; 57%) of 5b via the present route was improved in comparison to that of the previously reported functionalized aldehyde 5a (7 steps from 10; 13%). By applying the modified Julia coupling method, selectivity (6E/6Z=20 1-26 1) toward the (6E)-form of the coupled products (15 or 19) against the corresponding (6Z)-form was improved in comparison to the Wittig method (6E/6Z=4 1-6.9 1).