Cyclopamine 是一种致畸类固醇生物碱，通过靶向 Smoothened (Smo) 受体来抑制 Hedgehog (Hh) 信号通路。使用合成小分子抑制 Hh 信号传导一直被视为治疗癌症的一种治疗方法。我们在此报告了基于两阶段中继策略的环杷明的不对称合成。第一阶段：通过收敛方法全合成藜芦胺，其中应用关键的光诱导激发态纳扎罗夫反应来构建 C-nor-D-同型类固醇的基本 [6-6-5-6] 骨架。第二阶段：通过一系列化学选择性氧化还原操作实现藜芦胺向环巴明的转化。

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 of chemo-selective redox manipulations.