Total Synthesis ofDMOA-Derived Meroterpenoids: AchievingSelectivity in the Synthesis of (+)-Berkeleyacetal D and (+)-PeniciacetalI

The synthesis of complex natural products requires efficient control over chemoselectivity, stereoselectivity, and regioselectivity. Berkeleyacetals, a subfamily of 3,5-dimethylorsellinic acid (DMOA)-derived meroterpenoids, pose substantial synthetic challenges due to their densely functionalized and highly oxidized architectures, which have constrained synthetic efforts. Here, we present the first total synthesis of this class of DMOA-derived meroterpenoids, specifically (+)-berkeleyacetal D and (+)-peniciacetal I. Our approach features a chemoselective deprotonation followed by an intramolecular single-electron transfer (SET) from an enolate to an alkyl bromide, enabling the construction of the 2,3-dihydrofuran ring in berkeleyacetal D. Additional selective transformations include an <i>endo</i>-selective intramolecular Diels–Alder reaction, chemoselective methylations and semihydrogenation of [3]dendralene, and a solvent-controlled diastereoselective epoxidation. Beyond providing a synthetic route to these densely congested natural products, our study offers mechanistic insights into achieving selectivity in the assembly of architecturally demanding molecules.