A synthetic approach to the phorboxazoles – Synthesis of the C20–C32 central core

An enantiospecific synthesis of the C20–C32 central core of the phorboxazole scaffold, including the non-macrocyclic oxazole is detailed in 17 steps (longest linear sequence) from methacrolein in 7.8% overall yield. All of the stereocenters are communicated from a single Evans aldol reaction, and the final compound is suitably functionalized for further elaboration to the natural products.