近日，法国斯特拉斯堡大学Amir H. Hoveyda团队报道了用小方法集研究复杂大环的发散性和可编程骨重构。这一研究成果发表在2026年4月2日出版的《科学》杂志上。

复杂有机大环分子的生物活性会因其三维结构轮廓的不同而出现难以预测的变化。

研究组提出一种精简、可编程且系统化的大环骨架重塑策略。其核心多样化平台（枢纽）是一种易于获得的大环烯烃或二烯烃。需要经过六种转化（其中除一种外均为催化反应）：通过大环开环/交叉烯烃复分解裂解一个环生成二烯；通过交叉烯烃复分解和烯丙基取代进行单单元链同系化；通过烯烃异构化和乙烯醇解进行单单元链剪切；以及通过大环关环烯烃复分解重新成环。这些方法实用、温和、高效且可迭代。通过一个发散式反应网络，从二烯枢纽出发，平均每步即可获得一个类似物，成功合成了抗癌药物埃博霉素C（主要模型大环分子）的14个类似物。

附：英文原文

Title: Divergent and programmable skeletal remodeling of complex macrocycles with a small method set

Author: Ali Nikbakht, Xinghan Li, Jing Wan, Can Qin, Amir H. Hoveyda

Issue&Volume: 2026-04-02

Abstract: The bioactivity of complex organic macrocycles can vary unpredictably with their three-dimensional structural contours. Here, we present a streamlined, programmable and systematic strategy for skeletal remodeling of large organic rings. The central diversification platform (hub) is a readily available macrocyclic olefin or a diene. Six transformations, all but one catalytic, are needed: macrocyclic ring-opening/cross-metathesis for cleaving a ring to generate a diene, cross-metathesis and allylic substitution for one-unit chain homologation, alkene isomerization and ethenolysis for one-unit chain clipping, and macrocyclic ring-closing metathesis for reforming a ring. The methods are practical, mild, efficient, and amenable to iteration. Fourteen analogs of anti-cancer agent epothilone C (the primary model macrocycle) were accessed through a divergent network of reactions that correspond to an average of three steps per analog from the diene hub.

DOI: aee3540

Source: https://www.science.org/doi/10.1126/science.aee3540