Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters

Bastimolide B is a polyhydroxy macrolide isolated from marine cyanobacteria displaying antimalarial activity. It features a dense array of hydroxylated stereogenic centers with 1,5-relationships along a hydrocarbon chain. These 1,5-polyols represent a particularly challenging motif for synthesis, as the remote position of the stereocenters hampers stereocontrol. Herein, we present a strategy for 1,5-polyol stereocontrolled synthesis based on iterative boronic ester homologation with enantiopure magnesium carbenoids. By merging boronic ester homologation and transition-metal-catalyzed alkene hydroboration and diboration, the acyclic backbone of bastimolide B was rapidly assembled from readily available building blocks with full control over the remote stereocenters, enabling the total synthesis to be completed in 16 steps (LLS).

Automated summary

This study presents a strategy for the stereocontrolled synthesis of 1,5-polyols using enantiopure magnesium carbenoids. By merging boronic ester homologation and transition-metal-catalyzed alkene hydroboration and diboration, the acyclic backbone of bastimolide B was rapidly assembled with full control over the remote stereocenters.