Asymmetric total synthesis of benzenoid cephalotane-type diterpenoids through a cascade C(sp2) & C(sp3)–H activation

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-05-20 DOI:10.1038/s41467-025-59816-w

Xiangxin Li, Zhaoxu Lu, Shaocong Liu, Mengyao Sun, Shengfu Duan, Zhixiang Xie

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Abstract

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(sp²) and C(sp³)–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(sp²)–C(sp³) bonds and one C(sp³)–C(sp³) 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.

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C（sp2）和C(sp3) -H级联活化不对称全合成苯类头孢烷型二萜

头孢烷二萜类化合物因其独特复杂的碳骨架和显著的抗肿瘤活性而受到越来越多的关注。本文报道了含相同的6/6/6/5四环和不同氧化态的桥接δ-内酯骨架的苯类头孢烷型二萜的不对称和发散全合成。C（sp2）和C(sp3) -H级联活化通过关键的钯/ nbe共催化工艺高效制备了具有特征和合成挑战性的6/6/6/ 6/5四环骨架。该策略的特点是在一个步骤中构建了三个C -C键(两个C(sp2) -C （sp3）键和一个C（sp3) -C （sp3）键），并形成了两个具有两个手性中心的环。通过后期修饰的头孢烷内酯A-D（1-4）和头孢烷内酯B(5)的简洁和不对称全合成，证明了该方法在苯类头孢烷型二萜骨架的快速组装中的应用。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.