Total synthesis of cassane-type diterpenoid pikrosalvin

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.