Key Laboratory of Bioorganic Chemistry and Molecular Engineering, Ministry of Education and Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518055, China.
J Am Chem Soc. 2023 Sep 20;145(37):20202-20207. doi: 10.1021/jacs.3c08039. Epub 2023 Sep 8.
The alkaloids are highly complex steroidal alkaloids characterized by their intricate structural and stereochemical features and exhibit a diverse range of pharmacological activities. A new synthetic pathway has been developed to access this family of natural products, which enabled the first total synthesis of (-)-zygadenine. This synthetic route entails the construction of a hexacyclic carbon skeleton through a stereoselective intramolecular Diels-Alder reaction, followed by a radical cyclization. Subsequently, a meticulously designed sequence of redox manipulations was optimized to achieve the synthesis of this highly oxidized alkaloid.
生物碱是高度复杂的甾体生物碱，具有复杂的结构和立体化学特征，并表现出多种多样的药理活性。已经开发出一种新的合成途径来获得这一家族的天然产物，这使得 (-)- 猪毛菜碱的首次全合成成为可能。这条合成路线涉及通过立体选择性的分子内 Diels-Alder 反应构建一个六环碳骨架，然后进行自由基环化。随后，精心设计的氧化还原操作序列被优化，以实现这种高度氧化的生物碱的合成。
