Stereoselective synthesis of thailandamide A methyl ester

Org Biomol Chem. 2024 Feb 14;22(7):1409-1419. doi: 10.1039/d3ob02107f.

Abstract

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.