Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Nat Commun. 2024 Sep 2;15(1):7639. doi: 10.1038/s41467-024-52134-7.
The Veratrum alkaloids are a class of highly intricate natural products renowned for their complex structural and stereochemical characteristics, which underlie a diverse array of pharmacological activities ranging from anti-hypertensive properties to antimicrobial effects. These properties have generated substantial interest among both synthetic chemists and biologists. While numerous advancements have been made in the synthesis of jervanine and veratramine subtypes over the past 50 years, the total synthesis of highly oxidized cevanine subtypes has remained relatively scarce. Building on the efficiency of our previously developed strategy for constructing the hexacyclic carbon skeleton of the Veratrum alkaloid family via a stereoselective intramolecular Diels-Alder reaction and radical cyclization, here we show the development of a unified synthetic approach to access highly oxidized Veratrum alkaloids. This includes the total synthesis of (-)-zygadenine, (-)-germine, (-)-protoverine and the alkamine of veramadine A, by capitalizing on a meticulously designed sequence of redox manipulations and a late-stage neighboring-group participation strategy.
藜芦生物碱是一类高度复杂的天然产物，以其复杂的结构和立体化学特征而闻名，具有从抗高血压特性到抗菌作用等多种药理学活性。这些特性引起了合成化学家与生物学家的浓厚兴趣。尽管在过去的 50 年中，杰瓦宁和藜芦胺亚型的合成已经取得了许多进展，但高度氧化的塞瓦宁亚型的全合成仍然相对较少。基于我们之前开发的通过立体选择性分子内 Diels-Alder 反应和自由基环化构建藜芦生物碱家族六环碳骨架的策略的效率，我们展示了一种通用的合成方法来获得高度氧化的藜芦生物碱。这包括通过精心设计的氧化还原操作序列和后期邻基参与策略，实现(-)-藜芦定、(-)-germine、(-)-普罗托维因以及 veramadine A 的烷胺的全合成。
