Synthesis of Taxol’s complicated cousin
Propellane molecules contain three rings that all share a common edge, thereby collectively resembling a propeller. Canataxpropellane, a yew-derived natural product related to the cancer drug Taxol, is unusual in that it has two different propellane motifs in its backbone. Schneider et al. report a chemical synthesis of this intricate compound in under 30 steps. Key features of the route include a Diels-Alder reaction rendered asymmetric by introduction of a chiral silyl auxiliary, followed by a photochemical cycloaddition to establish the cyclobutane core.
Science, this issue p. 676
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.
- Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2) – Science Magazine
- England coronavirus testing has not risen fast enough – science chief – The Guardian
- Coronavirus Tests Science’s Need for Speed Limits – The New York Times
- Trump Falsely Distorts New York Times COVID-19 Science Story – FactCheck.org
- This is the brightest supernova ever seen – Science Magazine
- Coronavirus Today: Science will save us – Los Angeles Times
- Italians stuck at home are measuring light pollution for ‘science on the balcony’ – TechCrunch
- ‘Oumuamua might be a shard of a broken planet – Science News
- College of Arts and Science converts thriving academic programs to departments – Vanderbilt University News