Decoding Guaianolide Biosynthesis: Synthetic Insights into Pseudoguaianolides and Seco-Guaianolides.

The biosynthetic pathways leading to pseudoguaianolides and seco-guaianolides remain unclear. In this work, we demonstrate that highly oxidized 8,12-guaianolides serve as unprecedented precursors, enabling chemoselective, one-step access to pseudoguaianolide, seco-guaianolide, and xanthanolide-type sesquiterpenoids. Key mechanistic insights reveal the pivotal role of peroxide substituents on the guaianolide core and stereoelectronic factors in controlling reaction outcomes. These findings shed light on guaianolide selectivity and may mirror actual biosynthetic pathways, offering transformative potential for oxidative transformations in sesquiterpenoid synthesis.