Total Synthesis of Bryostatin 1
Total Synthesis of Bryostatin 1
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DOI：
10.1021/ja110198y
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发表时间：
2011-02-02
影响因子：
15
通讯作者：
Covel, Jonathan A.
中科院分区：
文献类型：
--
作者：
Keck, Gary E.;Poudel, Yam B.;Covel, Jonathan A.
Bryostatin 1是一种海洋天然产物，是一种非常有前景的先导化合物，因为它对多种人类疾病状态表现出强大的生物活性。我们在这里描述了该试剂的首次全合成。所采用的合成路线是一条高度收敛的路线，其中预先形成的、高度官能化的吡喃环A和C通过“吡喃环化”结合在一起，“吡喃环化”是A环片段上附加的羟基烯丙基硅烷与C环片段中的醛之间的TMSOTf促进反应，伴随着B环的形成。对得到的高度官能化的中间体的进一步阐述包括大内酯内酯化和选择性切割五个酯键中的一个。
Bryostatin 1 is a marine natural product that is a very promising lead compound because of the potent biological activity it displays against a variety of human disease states. We describe herein the first total synthesis of this agent. The synthetic route adopted is a highly convergent one in which the preformed, heavily functionalized pyran rings A and C are united by "pyran annulation", the TMSOTf-promoted reaction between a hydroxyallylsilane appended to the A-ring fragment and an aldehyde contained in the C-ring fragment, with concomitant formation of the B ring. Further elaborations of the resulting very highly functionalized intermediate include macrolactonization and selective cleavage of just one of five ester linkages present.