英国剑桥大学Gaunt, Matthew J.团队近日研究了烯烃的单碳同源性。相关论文于2025年5月20日发表在《自然》杂志上。

单碳同系物是结构相关且功能相同的有机分子，其链长相差一个亚甲基（-CH2-）单元。在许多类别的分子中，包括药物、天然产物、农用化学品、香料和石油产品，同源系列成员所表现出的物理化学特性在化合物之间存在细微差异，这可能会使它们的功能产生显著差异。因此，高效生成同源物是分子发现计划中的一项重要策略。尽管有几种官能团的同源化策略，但烯烃中一个碳链延伸的直接和通用方法仍然是一种未满足的合成需求。 

研究组报道了一种催化单碳同系物过程，该过程对简单和复杂分子中的许多类烯烃都有效。通过利用新型多面烯丙基砜试剂的内在反应性，这种简化的一锅法涉及交叉复分解和裂解/反烯级联，正式将一个亚甲基单元插入烯烃链。

在将这一过程应用于几种结构和功能复杂的分子中，研究组展示了这种实际转化如何产生以前未被探索的环孢菌素-A同源物。这些同源物显示出调节的药理学和生物学特性，可以作为亲环素抑制剂提供有前景的线索，这是一个在许多疾病领域具有巨大潜力的靶标。

附：英文原文

Title: One-carbon homologation of alkenes

Author: Grocott, Marcus C., Gaunt, Matthew J.

Issue&Volume: 2025-05-20

Abstract: One-carbon homologs are structurally-related and functionally-identical organic molecules, whose chain-lengths differ by a single methylene (–CH2–) unit1. Across many classes of molecule–including pharmaceutical agents, natural products, agrochemicals, fragrances and petroleum products–the physicochemical characteristics displayed by members of a homologous series subtly differ from one compound to another, which can impart remarkable differences to their function2. The efficient generation of homologs is, therefore, an important strategy in molecular discovery programs3,4. Despite the availability of homologation strategies for several functional groups5,6, direct and general methods for one-carbon chain extension in alkenes remain an unmet synthetic need7,8. We report a catalytic one-carbon homologation process that is effective for many classes of alkene in simple and complex molecules. By leveraging the intrinsic reactivity of a novel multifaceted allyl-sulfone reagent, a streamlined one-pot process, involving cross-metathesis and a fragmentation/retro-ene cascade, formally inserts a single methylene unit to the alkene chain. Amongst applications of this process to several structurally and functionally complex molecules, we demonstrate how this practical transformation generates previously unexplored homologs of Cyclosporine-A9. These homologs show modulated pharmacological and biological properties and could provide promising leads as cyclophilin inhibitors, a target that has great potential in many disease areas10.

DOI: 10.1038/s41586-025-09159-9

Source: https://www.nature.com/articles/s41586-025-09159-9