Enantioselective Total Synthesis of Breviones Utilizing a Bio‐Inspired Skeletal Editing Strategy

作者：Yaqian Liu, Yuanjun Zhou, Yan Xu, Shuangning Liu, Qingyang Huang, Hongli Jia, Houhua Li · 发表于：Angewandte Chemie International Edition · 年份：2026 · DOI：10.1002/anie.4698250 · 被引用次数：1 · 研究领域：Chemical synthesis and alkaloids、Plant biochemistry and biosynthesis、Phytochemistry and biological activities of Ficus species

ABSTRACT Inspired by skeletal editing transformations in the biosynthesis of spiro diterpene pyrones, we herein present an enantioselective total synthesis of the meroditerpenoids breviones B, C, and N. Our synthetic strategy features a series of bio‐inspired skeletal editing transformations, including a Dowd–Beckwith ring expansion to construct the seven‐membered A‐ring, and an annulative skeletal rearrangement that couples terpene and α‐pyrone motifs into the spiro diterpene pyrone framework. This latter transformation involves a novel dihydropyran‐to‐dihydrofuran ring contraction, a strategy that has proven applicable to a diverse range of terpene and pyrone fragments. In addition, during the synthesis, we also developed a SnCl 4 ‐mediated intramolecular hydroalkylation of alkenyl β‐keto esters, which enables the concurrent assembly of the fused B/C ring system along with three contiguous stereocenters.