Jin Yuan, Hok Sovanneary, Bacsa John, Dai Mingji
Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
Department of Pharmacology and Chemical Biology, Emory University, Atlanta, Georgia 30322, United States.
J Am Chem Soc. 2024 Jan 24;146(3):1825-1831. doi: 10.1021/jacs.3c13492. Epub 2024 Jan 16.
We report a convergent and efficient total synthesis of the C- D- steroidal alkaloid (+)-heilonine with a hexacyclic ring system, nine stereocenters, and a -hydrindane moiety. Our synthesis features four selective C-H functionalizations to form key C-C bonds and stereocenters, a Stille carbonylative cross-coupling to connect the AB ring system with the DEF ring system, and a Nazarov cyclization to construct the five-membered C ring. These enabling transformations significantly reduced functional group manipulations and delivered (+)-heilonine in 11 or 13 longest linear sequence (LLS) steps.
我们报道了具有六元环系统、九个立体中心和一个氢化茚部分的C-D甾体生物碱(+)-海洛宁的汇聚式高效全合成。我们的合成方法具有四个选择性C-H官能团化反应以形成关键的C-C键和立体中心，一个用于连接AB环系统与DEF环系统的Stille羰基交叉偶联反应，以及一个用于构建五元C环的Nazarov环化反应。这些关键转化显著减少了官能团操作，并以11步或13步最长线性序列（LLS）合成了(+)-海洛宁。
