College of Chemistry, Sichuan University, 29 Wangjiang Rd., Chengdu, Sichuan, 610064, China.
Angew Chem Int Ed Engl. 2023 Jul 17;62(29):e202305516. doi: 10.1002/anie.202305516. Epub 2023 Jun 12.
We have accomplished the total synthesis of sculponin U, a polycyclic C-20-oxygenated kaurane diterpenoid featuring a 7,20-lactone-hemiketal bridge, through a radical cascade cyclization triggered by photoinduced electron transfer (PET) of a silyl enolate to form the cyclohexanone-fused bicyclo[3.2.1]octane skeleton. Other key points in our synthetic strategy encompass a Diels-Alder reaction to construct the middle six-membered ring of sculponin U, and an intramolecular radical cyclization induced by iron-catalyzed hydrogen atom transfer to close the western cyclohexane ring. Successful preparation of the enantiopure silyl enolate as the PET precursor enables the asymmetric total synthesis of sculponin U, opening a new avenue for divergent syntheses of structurally related C-20-oxygenated kaurane congeners and pharmaceutical derivatives thereof.
我们通过硅基烯醇醚的光诱导电子转移（PET）引发的自由基级联环化反应，成功地全合成了 sculponin U，这是一种具有 7,20-内酯-半缩醛桥的多环 C-20-氧化贝壳杉烷二萜，形成了环己酮稠合的双环[3.2.1]辛烷骨架。我们的合成策略中的其他关键点包括 Diels-Alder 反应构建 sculponin U 的中环六元环，以及铁催化的氢原子转移诱导的分子内自由基环化反应以封闭西部环己烷环。成功制备作为 PET 前体的对映纯硅基烯醇醚，使得 sculponin U 的不对称全合成成为可能，为结构相关的 C-20-氧化贝壳杉烷同系物及其药物衍生物的发散合成开辟了新途径。
