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 (2) was assembled in two steps using a Diels–Alder/ortho-alkene-arene photocycloaddition sequence. Enantioselectivity was introduced by designing chiral siloxanes to serve as auxiliaries in the Diels–Alder reaction.

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.

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.