Stereoselective synthesis of thailandamide A methyl ester.

A convergent strategy for the stereoselective synthesis of the methyl ester of the structurally challenging and highly labile antibacterial polyene polyketide natural product thailandamide A has been developed. The key steps include the Zincke aldehyde reaction, Stille cross coupling, Negishi reaction, Julia-Kocienski olefination, cross metathesis, and the less explored Pd(I)-based Heck coupling to access different unsaturation bonds. Additionally, Urpi acetal aldol, Evans methylation, and Crimmins acetate aldol reactions were employed to construct four out of six asymmetric centers of the molecule.

Total Synthesis of Antibacterial Macrolide Sorangiolide A.

A convergent route for the asymmetric total synthesis of antibacterial macrolide sorangiolide A has been developed for the first time. The key feature of this synthesis includes Krische iridium-catalyzed anti-diastereoselective carbonyl crotylation, Crimmins acetate aldol, Yamaguchi esterification, Julia-Kocienski olefination, Horner-Wadsworth-Emmons olefination, and ring-closing metathesis. The origin of the low intensity of the 13C{1H} NMR signals of the C1 and C2 centers of the natural product has been investigated, disclosing possible forms of existence for the natural product in the solution phase.

Total Synthesis of Strasseriolide A.

Stereoselective total synthesis of structurally intriguing antimalarial macrolide strasseriolide A has been accomplished by adopting a convergent approach. The salient features of this synthesis include Co(BH4)2-mediated selective reduction of conjugated olefin, Crimmins propionate aldol, Evans alkylation, intermolecular Horner-Wadsworth-Emmons olefination, Yamaguchi macrolactonization, and selective saponification of ester moiety in the presence of a lactone functionality. The 13C{1H} NMR data of strasseriolide A were found to be very sensitive to its solution concentration.

Biselyngbyolides A & C: their total synthesis and anticancer activities.

Convergent strategies for the first total synthesis of biselyngbyolide C and an alternative route for the total synthesis of biselyngbyolide A have been developed. The key strategic feature in this study is Heck macrocyclization. The use of intramolecular Heck coupling for biselyngbyolide B was demonstrated by us earlier; however such a strategy has not been explored further for the other members of this family of natural products, in particular, where sensitive skipped olefins are involved. The other highlights of this synthetic study include iterative Crimmins acetate aldol and Wittig olefination processes, followed by the less explored cobalt-hydride-based reduction of an activated olefin and Shiina esterification. Our synthetic study enabled us to amend the reported NMR data of biselyngbyolides A and C. An evaluation of the anticancer activities of both biselyngbyolides A and C revealed that the apoptosis generated in cancer cells followed an intrinsic pathway.