Synthetic Studies on Taxane Diterpenoids and their Analogous Compounds

在现有的紫杉烷三碳环构造方法的基础上，研究了紫杉烷二萜的全合成。（+）-taxusin的对映选择性全合成是通过以下转化进行的：(1)对映选择性共轭加成异丁酯烯酸酯到烯酮上，(2)构建三羧基，(3)在DELTA^<3.8>-双键上进行环丙化，(4)环丙基酮还原裂解引入19-Me，(5)引入5- oh和C-4羰基甲基化。紫杉醇的对映选择性全合成是一个更有趣和重要的目标，通过使用3-溴-环己二烯-2-碳基作为C片段，它与光学纯的a片段偶联得到三碳前体。B环环化后，C片段的二烯部分经单线态氧氧化转化为4,7-二醇，然后0-0键断裂。在适当保护1,2和7,9-二醇基团后，通过与红豆杉素合成相似的方法引入19-甲基，所得烯醇在碱性条件下转化为愿望酮。适当的官能团操作，包括D环的构建，使我们以对映选择性的方式有效地合成了(-)-紫杉醇。另一方面，利用苯甲醚C片段计划了紫杉碱的全合成，合成了含C烯酮片段的三碳环。目前正在将这种中间体转化为紫杉醇。

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.