The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation
The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation
复制标题
DOI：
10.1038/nature07046
复制
发表时间：
2008-06-26
期刊：
影响因子：
64.8
通讯作者：
Stoltz, Brian M.
中科院分区：
文献类型：
--
作者：
Enquist, John A., Jr.;Stoltz, Brian M.
双催化对映体选择性转化是一种强有力的合成方法，可以在一次操作(1，2)中构建具有立体化学结构的复杂分子。除了在一次反应中产生两个或多个立体中心外，与类似的单一转化相比，多个不对称反应还增加了最终产物的对映体过剩(3-6)。此外，多个不对称操作有可能独立地在同一分子支架内的远程点构建几个立体中心，而不是依赖于反应位置(1)附近的预先存在的手性中心。尽管多重催化对映体选择性反应具有固有的优点，但它们在天然产物全合成中的应用仍然很大程度上没有得到充分利用。在这里，我们报告了使用双立体消融(7)对映体选择性烷基化反应在海洋二萜(-)-氰基硫杂黄素F(参考文献)的简明合成。8)。通过使用一种在单一立体收敛操作中独立、选择性地形成两个立体中心的技术，我们证明了外消旋和中非对映异构体的复杂混合物可以顺利地转化为具有特殊对映体过剩的合成有用的中间体。通过这种催化转化产生的立体化学信息有助于轻松、快速地完成这一海洋天然产物的全合成。
Double catalytic enantioselective transformations are powerful synthetic methods that can facilitate the construction of stereochemically complex molecules in a single operation(1,2). In addition to generating two or more stereocentres in a single reaction, multiple asymmetric reactions also impart increased enantiomeric excess to the final product in comparison with the analogous single transformation(3-6). Furthermore, multiple asymmetric operations have the potential to independently construct several stereocentres at remote points within the same molecular scaffold, rather than relying on pre- existing chiral centres that are proximal to the reactive site(1). Despite the inherent benefits of multiple catalytic enantioselective reactions, their application to natural product total synthesis remains largely underutilized(2). Here we report the use of a double stereoablative(7) enantioselective alkylation reaction in a concise synthesis of the marine diterpenoid ( -)-cyanthiwigin F ( ref. 8). By employing a technique for independent, selective formation of two stereocentres in a single stereoconvergent operation, we demonstrate that a complicated mixture of racemic and meso diastereomers may be smoothly converted to a synthetically useful intermediate with exceptional enantiomeric excess. The stereochemical information generated by means of this catalytic transformation facilitates the easy and rapid completion of the total synthesis of this marine natural product.