This paper presents the first successful total synthesis of pikrosalvin, a compound naturally derived from Salvia officinalis, grounded on the structural framework delineated by Brieskorn and Fuchs. Our synthetic approach was underpinned by a biomimetic strategy inspired by the Stork–Eschenmoser hypothesis for the biosynthesis of terpenes via polyene cyclization. Starting with commercially available vanillic acid and geraniol, we strategically assembled pikrosalvin's structural core, consisting of a decalin A/B ring, an aromatic C ring, and a butyrolactone D ring. Challenges related to protective groups and specific catalytic conditions were effectively addressed, resulting in high product yields. We further demonstrated the efficacy and broad applicability of a combined-acid-catalyzed polyene cyclization methodology in the context of complex natural product synthesis. This study sets the stage for future biological and pharmacological investigations of pikrosalvin.

中文翻译：

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酪烷型二萜吡罗萨尔文的全合成

本文基于 Brieskorn 和 Fuchs 描述的结构框架，首次成功全合成了 pikrosalvin，这是一种从丹参中天然提取的化合物。我们的合成方法以仿生策略为基础，该策略受到通过多烯环化生物合成萜烯的 Stork-Eschenmoser 假说的启发。从市售香草酸和香叶醇开始，我们策略性地组装了pikrosalvin的结构核心，由十氢萘A/B环、芳香族C环和丁内酯D环组成。与保护基团和特定催化条件相关的挑战得到有效解决，从而实现了高产品收率。我们进一步证明了联合酸催化多烯环化方法在复杂天然产物合成中的功效和广泛适用性。这项研究为 pikrosalvin 未来的生物学和药理学研究奠定了基础。