Total Synthesis of Aplyronine C

A highly stereocontrolled total synthesis of the cytotoxic marine macrolide aplyronine C is described. The route exploits aldol methodology to install the requisite stereochemistry and features a crucial boron-mediated aldol coupling of an N-vinylformamide-bearing methyl ketone with a macrocyclic aldehyde to introduce the full side chain. The synthesis of two novel C21-C34 side chain analogs is also reported.