Concise Synthesis of Complex Taxane Diterpene Canataxpropellane by Photochemical Dearomatization

Abstract

A concise synthesis of canataxpropellane.Abstract: Canataxpropellane belongs to the medicinally very important taxane diterpene family. The most prominent congener Taxol ® is a blockbuster drug and one of the most commonly used anti-cancer agent in clinics today. Canataxpropellane exhibits a novel taxane skeleton with an unparalleled molecular complexity. Unfortunately, its isolation from natural sources is inefficient to the extent, that biological evaluations are rendered impossible. Here, we describe the first total synthesis of canataxpropellane from inexpensive starting materials in 26 chemical transformations and 19 isolated synthetic intermediates. The scope of our work goes well beyond a "purely academic" endeavour, since detailed investigations into the pharmaceutical profile of this novel taxane skeleton are now practicable, as well as access to synthetic analogues for SAR studies.