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Synthetic Studies on Taxane Diterpenoids.

紫杉烷二萜的合成研究。

基本信息

批准号：
04403008
负责人：
KUWAJIMA Isao
金额：
$ 19.78万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

We have designed a total synthesis of taxol as the optically pure form. Our strategy was highly dependent on the 8-membered B ring cyclization between dienol ethers and acetal, and it was realized at earlier stage by using model compounds containing aromatric C ring to produce the desired endo tricarbocycle with correct stereochemistry. Our next problem was how to make an optically pure alpha-hydroxyaldehyde as A ring fragment which may play important roles to control the enantioselectivity at each site. For such purpose, we developed a useful synthetic method of optically pure A ring fragment by employing Sharpless AD methodology to cyclohexanedione-aldehyde derivative. Further, a useful method for introduction of 7-OH group was also explored.By combing these results, A fragment was connected with two types of C fragments such as cyclohexenone or anisol derivative, and then B ring cyclization was examined. The reaction took place nicely to give the desired tricarbocycles in good yields with correct stereochemistry. Stereoselective introduction of 7-OH group was readily performed by using our above methodology and we have succeeded to prepare two types of useful synthetic intermediates for taxol in optically pure forms. Both intermediates will be easily converted by applying the following transformation ; introduction of 1) C-8 methyl and 2) C-10 OAc group, 3) construction of D ring, and 4) acylation of C-13 hydroxy group.Since most of them are already dissolved by us and others, it will be very promising to complete an efficient total synthesis of taxol in a near future.It has also been proved our B ring cyclization methodology is very useful for the synthesis of taxusin and taxinine, and their synthetic studies will also complete in a short time.

我们设计了光学纯紫杉醇的全合成方法。我们的策略高度依赖于二烯醇醚和缩醛之间的八元B环环的环化反应，并且通过使用含芳香C环的模型化合物来产生所需的具有正确立体化学的内三碳环，在早期阶段实现了该策略。我们的下一个问题是如何使一个光学纯的α-羟基醛作为A环片段，这可能发挥重要作用，以控制在每个网站的对映选择性。为此，我们发展了一种利用Sharpless AD方法合成环己二酮醛衍生物的有效方法。结合这些结果，将A片段与环己烯酮或苯甲醚衍生物等两类C片段连接，然后考察B环的环化反应。反应顺利进行，以良好的产率得到具有正确立体化学的所需三碳环。利用上述方法，我们很容易地进行了7-OH基团的立体选择性引入，并成功地制备了两种类型的有用的光学纯形式的紫杉醇合成中间体。通过应用以下变换，两种中间体将容易地被转化：引入1）C-8甲基和2）C-10乙酸酯基团，3）D环的构建，和4）C-13羟基的酰化。由于它们中的大多数已经被我们和其他人溶解，我们的B环环化方法在紫杉醇的合成中具有重要的应用价值，红豆杉素和紫杉宁的合成研究也将在短期内完成。