Synthetic Study on Taxol via a New Route Inspired by Its Biogenesis

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In the synthetic study on taxol arose from the interest in its biosynthetic pathway found was the condition for the coupling reaction of the Left-Wing with the Right-Wing model compound, and the transformation of the coupled products to the substrate for the designed transannular reaction. Though the undesired product was the major product, the desired 10-membered ring formed in 10 % yield by the intramolecular pinacol coupling between C-9 and C-10. Hence, another position should be selected if the ring closure is to be carried out by the intramolecualr pinacol coupling. The B-ring closure by the intramolecular alkylation of the cyanohydrin was examined, too. Though its yield was not determined because the reaction was run in a small scale, almost no side products formed in this reaction. Hence, this method will be a promising one if the reaction condition is optimized.In the synthetic study on taxol directed towards its efficient synthesis found was that two model keto-aldehydes afforded the desired products in 12 % and 20 % (at 91 % conversion) yields. The keto-aldehyde possessing acetonide between C-9 and C-10 diol, which was designed to make the reaction points come closer, was also examined, but the corresponding diol was a sole product in this case. Another keto-aldehyde possessing sp^2 C-11 carbon was prepared and subjected to the intramolecular pinacol coupling, but no desired product was obtained.From the results obtained in this study, we recognized that a proper devise to promote the intramolecular pinacol coupling between C-9 and C-10 must be set in the substrate to achieve the efficient construction of B-ring. Hence, we are now investigating the intramolecular pinacol coupling of the substrate possessing a hydroxy group at C-16, because this hydroxy group would aid the substrate to take an endo boat-chair conformation in the transition state to afford the desired product.