First Total Synthesis of (−)-Principinol C

First Total Synthesis of (−)-Principinol C

Author: ChemistryViews

Principinol C (pictured) is a natural product that was isolated from the evergreen shrub Rhododendron principis. It has a complex structure with a 5/7/6/5 tetracyclic core and eight contiguous stereocenters. This makes the compound challenging to prepare, and so far, no total synthesis of principinol C had been reported.

Yanxing Jia, Peking University, Beijing, China, and colleagues have performed the first total synthesis of (−)-principinol C. The first prepared an enyne precursor from a bicyclo[3.2.1]octane derivative. Then, in a key step, an intramolecular Pauson–Khand reaction using Co2(CO)8 at 40–60 °C was employed to build the 7/5-bicyclic ring system of the target product. The desired tetracycle was obtained in 45 % yield. This transformation was followed by a methylation step and subsequent reduction/oxidation and protection/deprotection reactions to obtain the desired (−)-principinol C.

Overall, the team synthesized (−)-principinol C in 16 steps and 2.8 % overall yield starting from a bicyclo[3.2.1]octane ring system. Including the synthesis of the known bicyclo[3.2.1]octane ring system starting from a 2-cyclohexenone, the preparation took 21 steps and gave 0.6 % overall yield. According to the researchers, the work includes is the first application of the intramolecular Pauson–Khand reaction of an enyne to construct a 7,5-bicyclic ring system in natural product synthesis.


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