A formal asymmetric synthesis of apratoxin D via advanced-stage asymmetric ACC α,α-bisalkylation of a chiral nonracemic ketone

Abstract

A formal asymmetric synthesis of the marine natural product apratoxin D, a highly potent inhibitor of H-460 human lung cancer cell growth (IC50 value of 2.6nM), is described. The key feature of the synthesis is an advanced-stage asymmetric ACC α,α-bisalkylation of a chiral nonracemic methyl ketone to provide access to an advanced intermediate as a single diastereomer that has previously been advanced to apratoxin D.