Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
State Key Laboratory of Petroleum Molecular and Process engineering, SKLPMPE, Sinopec research institute of petroleum processing Co., LTD., Beijing 100083, China, East China Normal University, Shanghai 200062, China.
J Am Chem Soc. 2023 Nov 22;145(46):25086-25092. doi: 10.1021/jacs.3c10362. Epub 2023 Nov 10.
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. : 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--D--steroid. : conversion of veratramine to cyclopamine was achieved through a sequence of selective redox manipulations.
环巴胺是一种致畸甾体生物碱，通过靶向 Smoothened（Smo）受体抑制 Hedgehog（Hh）信号通路。用合成小分子抑制 Hh 信号已被作为治疗癌症的一种治疗方法进行研究。我们在此报告了基于两阶段接力策略的环巴胺的不对称合成。通过会聚方法实现了藜芦胺的总合成，其中关键的光致激发态纳扎罗夫反应被应用于构建 C-D-甾体的基本[6-6-5-6]骨架。通过一系列选择性氧化还原操作，将藜芦胺转化为环巴胺。
