近日，上海中医药大学Fabian Schneider团队研究了(−)-螺杂三酮A的全合成：二乙烯基环丙烷重排方法。相关论文于2025年10月16日发表在《科学》杂志上。

多重耐药病原体的兴起对全球健康构成重大威胁，其中耐甲氧西林金黄色葡萄球菌（MRSA）的防治挑战尤为严峻。一种具有前景的解决策略是利用小分子化合物使MRSA对现有药物恢复敏感性。

研究组报道了具有此类潜力的天然产物(−)-螺曲霉酮A的对映选择性全合成，该分子属于安地康素家族中结构复杂的梅罗萜类化合物。由于其高度功能化的多环骨架结构，该天然产物的合成研究长期面临挑战。研究组的合成路线具有以下特征：首先进行立体选择性狄尔斯-阿尔德环加成反应，继而通过关键的二乙烯基环丙烷重排反应构建螺双环[3.2.2]壬烷核心骨架——经密度泛函理论计算证实该重排反应具有可逆性。通过对致密笼状结构进行精准的后期官能化修饰，该研究不仅实现了目标天然产物的合成，还为阐明其与(−)-曲霉双酮之间可能存在的生物合成关联提供了证据。

附：英文原文

Title: The total synthesis of (-)-spiroaspertrione A: A divinylcyclopropane rearrangement approach

Author: Wenbo Huang, Lu Pan, Heng Zhao, Fabian Schneider, Tanja Gaich

Issue&Volume: 2025-10-16

Abstract: The rise of multidrug-resistant pathogens poses a major threat to global health, with methicillin-resistant Staphylococcus aureus (MRSA) among the most challenging. One promising approach to overcoming resistance is using small molecules that resensitize MRSA to existing drugs. Here, we report the enantioselective total synthesis of one such promising candidate, ()-spiroaspertrione A, a complex meroterpenoid of the andiconin family. This natural product has long eluded synthesis because of its densely functionalized polycyclic backbone. Our route features a stereoselective Diels-Alder cycloaddition, followed by a key divinylcyclopropane rearrangement forming the spirobicyclo[3.2.2]nonane core, which proved to be reversible and was further investigated by density functional theory calculations. Strategic late-stage functionalization of the compact cage architecture enabled access to the natural product and provided evidence for a plausible biosynthetic relationship with ()-aspermerodione.

DOI: adz7593

Source: https://www.science.org/doi/10.1126/science.adz7593