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 the antibacterial polyketide natural product thailandamide lactone.

Stereoselective total synthesis of the structurally intriguing polyketide natural product thailandamide lactone was accomplished, and done so using a convergent approach for the first time to the best of our knowledge. The key features of this synthesis included use of a Crimmins acetate aldol reaction, Evans methylation, Urpi acetal aldol reaction, Sharpless asymmetric epoxidation and subsequent γ-lactonization for the installation of six asymmetric centers and the use of the Negishi reaction, Julia-Kocienski olefination, cross metathesis, HWE olefination and intermolecular Heck coupling for construction of a variety of unsaturated linkages. Pd(i)-based Heck coupling was introduced, for the first time to the best of our knowledge, quite efficiently to couple the major eastern and sensitive western segments of the molecule. The antibacterial activity of thailandamide lactone was also evaluated.