Formal Total Synthesis of (–)-Taxol

Formal Total Synthesis of (–)-Taxol

Author: Claire D'Andola

Taxol, isolated from the bark of the Pacific yew tree (Taxus brevifolia), displays potent bioactivity and has been widely used as an anticancer drug. The complex structure of taxol, which includes a highly distorted 6-8-6 taxane scaffold with nine stereogenic centers (including an all-carbon quaternary stereogenic center), diverse functional groups such as oxetane, trans-1,2-diol, acyloin, and a bridgehead double bond, combined with its biological properties has made it an attractive and challenging synthetic target.

The formation of the eight-membered carbocyclic ring, in particular, has been a significant problem in some previous syntheses because of its highly strained nature arising from transannular strain.

Masahisa Nakada and colleagues, Waseda University, Japan, have tackled these challenges by envisioning a convergent total synthesis of (–)-taxol. They prepare the initial building blocks of (–)-taxol in a parallel fashion, thus reducing time and also providing the advantage of the independent transformations of functional groups that are otherwise incompatible with each other. The problem of forming the eight-membered carbocyclic ring was then solved by using the palladium-catalyzed intramolecular alkenylation of a methyl ketone, thus affording the cyclized product in an excellent yield (96 %).

 

 

The nature of this convergent approach has the potential to enable the synthesis of diverse taxol derivatives and work is currently underway to reduce the number of synthetic steps.


 

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