Graduate School of Pharmaceutical Sciences, The University of Tokyo.
Chem Pharm Bull (Tokyo). 2024;72(4):360-364. doi: 10.1248/cpb.c24-00126.
Batrachotoxin (1) is a potent cardio- and neurotoxic steroid isolated from certain species of frogs, birds, and beetles. We previously disclosed two synthetic routes to 1. During our synthetic studies toward 1, we explored an alternative strategy for efficiently assembling its 6/6/6/5-membered steroidal skeleton (ABCD-ring). Here we report the application of intermolecular Weix and intramolecular pinacol coupling reactions. While Pd/Ni-promoted Weix coupling linked the AB-ring and D-ring fragments, SmI-mediated pinacol coupling did not cyclize the C-ring. Instead, we discovered that SmI promoted a 1,4-addition of the α-alkoxy radical intermediate to produce the unusual 11(9→7)-abeo-steroid skeleton. Thus, this study demonstrates the convergent assembly of the skeleton of the natural product matsutakone in 11 steps from 2-allyl-3-hydroxycyclopent-2-en-1-one.
蛙毒素（1）是一种从某些蛙类、鸟类和甲虫中分离出来的强效心脏和神经毒素甾体。我们之前已经公布了两种合成 1 的路线。在我们合成 1 的研究中，我们探索了一种高效组装其 6/6/6/5 元甾体骨架（ABCD 环）的替代策略。在这里，我们报告了分子间 Weix 和分子内频哪醇偶联反应的应用。虽然 Pd/Ni 促进的 Weix 偶联连接了 AB 环和 D 环片段，但 SmI 介导的频哪醇偶联没有环化 C 环。相反，我们发现 SmI 促进了α-烷氧基自由基中间体的 1,4-加成，生成了不寻常的 11(9→7)-abeo-甾体骨架。因此，这项研究展示了从 2-烯丙基-3-羟基环戊-2-烯-1-酮出发，经过 11 步反应，将天然产物 matsutakone 的骨架进行收敛性组装。
