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

在对紫杉醇的合成研究中引起了对其生物合成途径的兴趣，发现了左翼与右翼模型化合物偶联反应的条件，并将偶联产物转化为底物进行设计的跨环反应。虽然不需要的产物是主要产物，但通过C-9和C-10之间的分子内pinacol偶联，以10%的产率形成了所需的10元环。因此，如果要通过分子内pinacol偶联进行环闭合，则应选择另一个位置。还研究了氰醇分子内烷基化对b环闭合的影响。由于反应规模小，产率没有确定，但几乎没有副产物产生。因此，如果对反应条件进行优化，该方法将是一种很有前途的方法。在对紫杉醇进行高效合成的研究中发现，两种模型酮醛的产率分别为12%和20%（转化率为91%）。在C-9和C-10二醇之间含有丙酮的酮醛，其目的是使反应点更接近，但在这种情况下，相应的二醇是唯一的产物。制备了另一种含有sp^2 C-11碳的酮醛，并进行了分子内蒎醇偶联，但没有得到理想的产物。从本研究的结果中，我们认识到必须在底物中设置适当的装置来促进C-9和C-10之间的分子内pinacol偶联，以实现b环的有效构建。因此，我们现在正在研究在C-16上具有羟基的底物的分子内pinacol偶联，因为这个羟基可以帮助底物在过渡态中形成内端船椅构象，以提供所需的产物。

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.