Asymmetric Synthesis of Cyclopamine, a Hedgehog (Hh) Signaling Pathway Inhibitor
Asymmetric Synthesis of Cyclopamine, a Hedgehog (Hh) Signaling Pathway Inhibitor
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DOI：
10.1021/jacs.3c10362
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发表时间：
2023-11-10
影响因子：
15
通讯作者：
Gao，Shuanhu
中科院分区：
文献类型：
--
作者：
Shao，Hao;Liu，Wenheng;Gao，Shuanhu
Cyclopamine is a teratogenic steroidal alkaloid, which inhibits the Hedgehog (Hh) signaling pathway by targeting the Smoothened (Smo) receptor. Suppression of Hh signaling with synthetic small molecules has been pursued as a therapeutic approach for the treatment of cancer. We report herein the asymmetric synthesis of cyclopamine based on a two-stage relay strategy.Stage-I: total synthesis of veratramine through a convergent approach, wherein a crucial photoinduced excited-state Nazarov reaction was applied to construct the basic [6–6–5–6] skeleton of C-nor-D-homo-steroid.Stage-II: conversion of veratramine to cyclopamine was achieved through a sequence ofchemo-selective redox manipulations.
