Structure Investigations of (ent)-Cladospolide D by De Novo Synthesis and Kinetic and Thermodynamic Isomerization.

The de novo asymmetric synthesis of cladospolides B and C and ( ENT)-cladospolide D has been achieved from achiral non-1-yne. The 11-13-step route relies upon a Noyori reduction and a KAPA promoted alkyne zipper reaction to relay an achiral functionality across a nine-carbon fragment and to enable the installation of a dienoate functionality. A diastereo- and regioselective Sharpless dihydroxylation of a dienoate installed the remaining stereochemistry. The de novo asymmetric route allowed for the asymmetric synthesis of three members of the cladospolide natural products and correctly established the structure for cladospolide D. [ABSTRACT FROM AUTHOR]