De Novo Asymmetric Synthesis of Cladospolide B−D: Structural Reassignment of Cladospolide D via the Synthesis of its Enantiomer

Abstract

The enantioselective synthesis of cladospolide B, C, and (ent)-cladospolide D has been achieved in 11-15 steps from 1-nonyne. The route relies upon an alkyne zipper reaction to relay an ynone and dienoate functional groups across a nine carbon fragment, which enables a highly enantioselective Noyori ynone reduction and a diastereo- and regioselective Sharpless dihydroxylation of a dienoate. In addition to being a flexible approach to three members of the cladospolide natural products, this route for the first time correctly established the structure for cladospolide D.