Synthetic Studies on Taxane Diterpenoids and their Analogous Compounds

基于先前开发的紫杉烷三碳环构筑方法，对紫杉烷二萜类化合物的全合成进行了研究。对映体选择性全合成紫杉素的方法如下：(1)异丁酸酯与烯酮的不对称共轭加成反应；(2)三碳环的构筑；(3)Delta？-双键，(4)环丙基酮的还原裂解引入19-Me，(5)5-羟基的引入和C-4羰基的亚甲基化。紫杉醇的不对称全合成也是一个更有趣和重要的目标，以3-溴环己二烯-2-甲缩醛为C片段，它与光学纯的A片段偶联得到三碳环前驱体。在B环化后，C片段的二烯部分通过单线态氧氧化和0-0键的断裂转化为4，7-二醇。在适当保护1，2-和7，9-二醇部分后，通过与紫杉素合成类似的方法引入19-甲基，得到的烯醇在碱性条件下转化为所需的酮。通过适当的官能团操作，包括D环的构建，我们以对映体选择性的方式高效地合成了(-)-紫杉醇。另一方面，利用苯甲醚C片段进行了紫杉碱的全合成，并合成了含有C-烯酮片段的三碳环。这种中间体转化为紫杉碱的过程目前正在进行中。

Based on the methodology for construction of taxane tricarbocycles previously develop, total syntheses of taxane diterpenoids have been studied. Enantioselective total synthesis of (+)-taxusin has been performed by using the following transformations : (1)enantioselective conjugate addition isobutyric ester enolate to the enone, (2)construction of tricarbocycle, (3)cyclopropanation on DELTA^<3.8>-double bond, (4) reductive cleavage of cyclopropyl ketone to introduce 19-Me, (5)Introduction of 5-OH and methylenation of C-4 carbonyl group.Enantioselective total synthesis of taxol, a more interesting and important target, has also been achieved as follows, By using 3-bromo-cyclohexadiene-2-carbacetal was used as a C fragment, and its coupling with optically pure A fragment afforded a tricarbocycle precursor. After B ring cyclization, diene moiety of C fragment was converted to the 4,7-diol via singlet oxygen oxygenation followed by cleavage of the 0-0 bond. After appropriate protection of 1,2-and 7,9-diol moieties, 19-methyl group was introduced via a similar way with taxusin synthesis, the resulting enol was converted to the desire ketone under basic conditions. Appropriate functional group manipulation including D ring construction led us to an efficient synthesis of (-)-taxol in enantioselective manner.On the other hand, total synthesis of taxinine has been planed by using an anisole C fragment, and the tricarbocycle containing C enone fragment was synthesized. Conversion of this intermediate to taxinine is now in progress.