Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C by a Carbonyl Ylide Cycloaddition Strategy

Abstract

Ketal isomers avoided. The unique 2,8-dioxabicyclo[3.2.1]octane core of zaragozic acid C (1) was constructed in a Rh-catalyzed 1,3-dipolar cycloaddition of an alkyne to an ester carbonyl ylide. Another feature of this improved synthesis is the construction of the alkyl side chain at C1 by olefin cross-metathesis.