Li Xiangxin, Lu Zhaoxu, Liu Shaocong, Sun Mengyao, Duan Shengfu, Xie Zhixiang
State Key Laboratory of Applied Organic Chemistry & College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, China.
Nat Commun. 2025 May 20;16(1):4674. doi: 10.1038/s41467-025-59816-w.
Cephalotane diterpenoids, featuring unique and complicated carbon skeletons and remarkable antitumor activities from the Cephalotaxus genus, have been gaining increasing attention. Herein, we report the asymmetric and divergent total synthesis of benzenoid cephalotane-type diterpenoids containing the identical 6/6/6/5 tetracyclic and the bridged δ-lactone skeleton with different oxidation states. A cascade of C(sp) and C(sp)-H activation has been developed to efficiently prepare the characteristic and synthetically challenging 6/6/6/5 tetracyclic skeleton through a pivotal palladium/NBE-cocatalyzed process. The feature of this strategy is the construction of three C-C bonds (two C(sp)-C(sp) bonds and one C(sp)-C(sp) bond) and the formation of two cycles with two chiral centers in a single step. The application of this method for the rapid assembly of the skeleton of benzenoid cephalotane-type diterpenoids is demonstrated through the concise and asymmetric total synthesis of cephanolides A-D (1-4) and ceforalide B (5) via late-stage modification.
含有独特且复杂碳骨架以及显著抗肿瘤活性的三尖杉烷二萜类化合物，近年来受到越来越多的关注。本文报道了含相同6/6/6/5四环和桥连δ-内酯骨架且具有不同氧化态的苯并三尖杉烷型二萜类化合物的不对称发散全合成。我们开发了一系列C(sp)和C(sp)-H活化反应，通过关键的钯/降冰片烯共催化过程，高效制备了具有挑战性的6/6/6/5四环骨架。该策略的特点是一步构建三个C-C键（两个C(sp)-C(sp)键和一个C(sp)-C(sp)键）并形成两个带有两个手性中心的环。通过后期修饰对cephalolides A-D（1-4）和ceforalide B（5）进行简洁不对称全合成，证明了该方法在快速构建苯并三尖杉烷型二萜类化合物骨架中的应用。
