Total Synthesis and Structure Determination of Mycapolyol E Using Iterative Homologation of Boronic Esters

Mycapolyol E is a cytotoxic polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS) metabolite isolated from a marine sponge containing an extended polyacetate motif, terminal formamide moiety, and tetramic acid-derived headgroup, whose structure could not be fully elucidated upon isolation. A modular approach was employed and the ten 1,3-related hydroxy-substituted stereocenters were installed through iterative diboration/homologation reactions. Furthermore, the stereochemistry of the unassigned methyl stereocenter at C5 was elucidated through partial synthesis and nuclear magnetic resonance (NMR) analysis, and the uncertainty surrounding the relative stereochemistry of the 1,3-polyol was resolved. The stereochemistry and structure of mycapolyol E was confirmed through total synthesis, which was completed in 20 steps longest linear sequence (LLS).