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

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-10-16 DOI:10.1126/science.adz7593

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

引用次数: 0

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.

查看原文本刊更多论文

（−）-螺曲霉酮A的全合成：二乙烯基环丙烷重排法

耐多药病原体的增加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）是最具挑战性的。克服耐药性的一个有希望的方法是使用小分子使MRSA对现有药物重新敏感。在这里，我们报道了对映选择性的全合成这样一个有希望的候选人，(−)-spiroaspertrione A，一个复杂的苯乙烯家族的美罗萜类化合物。这种天然产物由于其密集功能化的多环主链而长期无法合成。我们的路线具有立体选择性Diels-Alder环加成，随后是关键的二乙烯基环丙烷重排形成螺环[3.2.2]壬烷核心，这被证明是可逆的，并通过密度泛函理论计算进一步研究。战略性的后期功能化紧凑的笼状结构使天然产物能够获得，并为与(−)-aspermerodione的合理生物合成关系提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

期刊介绍： Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research. Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated. Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.