Synthesis of precursors en route to the basic skeleton of the anti-tumor drug Taxol
In this work, a new and efficient synthesis of 9,9-dimethyl-bicyclo[3.3.1]nonane-2,6-dione (85), which is a potential precursor of the ABC ring skeleton of the anti-tumor drug taxol (1), has been synthesized by using a photochemical oxa-di-p-methane rearrangement as a key reaction. The next important step of this work was the cleavage of the central cyclopropane bond of 84. In order to achieve the wanted bond cleavage in 84, potassium-graphite intercalation compound (C8K) was applied to 84 so that conjugation of the carbonyls and lateral bonds were not any more the predominant factors for the cleavage of the cyclopropane. Similarly, a build-up of cationic intermediates will be avoided by this method which is known to proceed via diradical anions and 85 was synthesized.