Concise syntheses of cystothiazoles A, C, D, and melithiazol B.
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).
Iwaki
Yuki
Y
Research Institute, Novartis Pharma K.K, Tsukuba, Ibaraki 300-2611, Japan.
Akita
Hiroyuki
H
D000179:Acrylates / Q000138:chemical synthesis*; D000447:Aldehydes / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D000935:Antifungal Agents / Q000138:chemical synthesis*; D008956:Models, Chemical; D013844:Thiazoles / Q000138:chemical synthesis*
D000179:Acrylates; D000447:Aldehydes; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D013844:Thiazoles; C112182:cystothiazole A; C443723:cystothiazole C; C526158:cystothiazole D; C401243:melithiazol B