Total Synthesis of Novel Oxylipins: Plasmodiophorols A, C, and Epimers

In 2021, novel oxylipins plasmodiophorol A–C were identified as products of the hydroperoxide bicyclase activity of CYP50918A1 from Plasmodiophora brassicae (Rhizaria, SAR). Here, we report the first total syntheses of plasmodiophorol A and C in 12 and 13 steps, respectively, starting from chiral tetrahydro‐1H‐cyclopentafuranone. Key transformations included enzymatic desymmetrization, epimerization, and diastereoselective Grignard addition. Notably, during the synthesis of plasmodiophorol C, we also generated and structurally characterized a previously unknown compound. These synthetic routes provide reliable access to plasmodiophorols A and C, offering valuable standards for probing their biosynthetic pathways and facilitating their identification in marine biomasses. This work lays the foundation for further chemical and biological studies of these unique oxylipins.