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

紫杉醇生物起源启发的新路线合成研究

基本信息

批准号：
12672072
负责人：
NAKADA Masahisa
金额：
$ 1.86万
依托单位：
Waseda University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

在对紫杉醇的合成研究中，发现其生物合成途径的兴趣是发现左翼与右翼模型化合物的耦合反应的条件，以及耦合产物向底物的转化以供设计的跨媒介反应。尽管不希望的产物是主要产物，但所需的10元环通过C-9和C-10之间的分子内触摸曲霉偶联以10％的收率形成。因此，如果要通过leotemolecualr pinacol耦合执行环闭合，则应选择另一个位置。也检查了蓝糖蛋白分子内烷基化的B环闭合。尽管未确定其产量，因为反应是小规模运行的，但在此反应中几乎没有侧产物。因此，如果对反应条件进行了优化，则这种方法将是一种有希望的方法。在针对其有效合成的紫杉醇的合成研究中发现，两种模型酮醛为12％和20％（以91％的转换为91％）产生了所需的产品。还检查了酮醛在C-9和C-10二醇之间具有乙酰醛的酮，旨在使反应点更接近，但在这种情况下，相应的Diol是唯一的二醇。制备了另一种具有Sp^2 C-11碳的酮醛，并进行了分子内的小游戏偶联，但没有获得所需的产物。从这项研究中获得的结果，我们认识到，我们认识到，在C-9和C-10的建筑中促进了在C-9和C-10中促进c-9和c-10的二型在spertation seps spertity septity septif的效率。因此，我们现在正在研究具有C-16羟基的底物的分子内松（Pinacol）耦合，因为该羟基将有助于基板在过渡状态下采用送船椅，以提供所需的产品。