Total synthesis of thapsigargin, a potent SERCA pump inhibitor
Total synthesis of thapsigargin, a potent SERCA pump inhibitor
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DOI：
10.1021/ol062947x
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发表时间：
2007-02-15
期刊：
影响因子：
5.2
通讯作者：
Ley, Steven V.
中科院分区：
文献类型：
--
作者：
Ball, Matthew;Andrews, Stephen P.;Ley, Steven V.
thapsigargin的对映选择性总合成，一种有效的，选择性的Ca2+泵SERCA抑制剂，被描述。从酮醇8开始，关键步骤包括在C4-C5上区域选择性地引入内部烯烃，在C3上明智地选择保护基团以允许螯合控制的还原，以及在C3- o上化学选择性地引入天使酯功能。选择性酯化法完成了总共42步的总合成，总收率为0.61%（每步平均收率为88.6%）。
The enantioselective total synthesis of thapsigargin, a potent, selective inhibitor of the Ca2+ pump SERCA, is described. Starting from ketoalcohol 8, key steps involve regioselective introduction of the internal olefin at C4-C5, judicious protecting group choice to allow chelation-controlled reduction at C3, and chemoselective introduction of the angelate ester function at C3-O. A selective esterification approach completes the total synthesis in a total of 42 steps and 0.61% overall yield (88.6% average yield per step).