Total Syntheses of Phleghenrines A and C: A [4 + 2] Cycloaddition and Ring-Expansion Approach

The first total syntheses of Lycopodium alkaloids phleghenrines A and C have been accomplished in 19 and 18 steps, respectively, relying on three (hetero)-Diels–Alder ([4 + 2]) cycloaddition reactions to forge the cyclic molecular backbone and two ring-expansion reactions to manipulate the ring size. A chiral precursor is synthesized through an auxiliary controlled Diels–Alder reaction, rendering the asymmetric synthesis accessible. The established strategy provides a general approach to the relevant novel Lycopodium alkaloids.首次完成了石松生物碱（Lycopodium alkaloids）菲格灵碱A与C的全合成，总步数分别为19步与18步。该合成策略依托三步（杂）狄尔斯-阿尔德（Diels–Alder，[4+2]）环加成反应构建环状分子骨架，并通过两步扩环反应调控环系尺寸。研究通过助剂调控的狄尔斯-阿尔德反应合成手性前体，从而实现不对称合成。本研究所确立的合成策略可为相关新型石松生物碱的合成提供通用化路径。