Total synthesis of the complex taxane diterpene canataxpropellane.

Abstract

Canataxpropellane belongs to the medicinally important taxane diterpene family. The most prominent congener, Taxol, is one of the most commonly used anticancer agent in clinics today. Canataxpropellane exhibits a taxane skeleton with three additional transannular C-C bonds, resulting in a total of six contiguous quaternary carbons, of which four are located on a cyclobutane ring. Unfortunately, isolation of canataxpropellane from natural sources is inefficient. Here, we report a total synthesis of (-)-canataxpropellane in 26 steps and 0.5% overall yield from a known intermediate corresponding to 29 steps from commercial material. The core structure of the (-)-canataxpropellane (<b>2</b>) was assembled in two steps using a Diels-Alder/<i>ortho</i>-alkene-arene photocycloaddition sequence. Enantioselectivity was introduced by designing chiral siloxanes to serve as auxiliaries in the Diels-Alder reaction.