Zhao Rong, Zhao Xiaolong, Yang Ming
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou, Gansu Province, 730000, China.
Angew Chem Int Ed Engl. 2025 Feb 3;64(6):e202420507. doi: 10.1002/anie.202420507. Epub 2024 Dec 4.
Kalmanol (1) is the first isolated kalmane-type grayanoid featuring a highly oxidized 5/8/5/5 tetracyclic carbon skeleton and 9 contiguous stereocenters. We have accomplished the efficient and asymmetric total synthesis of 1 in 16 steps from known compounds (20 steps from commercially available starting materials) by a modular synthetic strategy. A tetracyclic intermediate was prepared in a convergent manner through a Grignard reaction and a subsequent ring-closing metathesis reaction of two enantiomerically enriched fragments. The polyhydroxy groups were introduced by late-stage stereo- and regioselective oxidations.
卡尔马诺醇（1）是首个分离得到的具有高度氧化的5/8/5/5四环碳骨架和9个相邻立体中心的半日花烷型木藜芦烷类化合物。我们采用模块化合成策略，从已知化合物出发，经16步反应（从市售起始原料出发为20步反应）高效且不对称地全合成了1。通过格氏反应以及随后两个对映体富集片段的闭环复分解反应，以汇聚方式制备了一个四环中间体。多羟基通过后期的立体和区域选择性氧化引入。
