3,5-Dimethylorsellinic acid (DMOA)-derived meroterpenoids are an extensive natural product family with significant structural complexity and diverse biological activity. Their structures feature various fused, bridged, spirocyclic skeletons and unconventional stereochemistries with significant strain, especially the trans-syn-trans fused drimane system, and extensive oxidative, skeletal rearrangements. Despite a long isolation history and extensive biosynthesis studies and encouraging biological activities, chemical synthesis of those natural products appeared only recently compared with other well-studied diterpene families such as the ent-kauranes, daphanes, and tiglianes. Thus, this thesis will present our work as an incremental advancement on the total syntheses of DMOA-derived meroterpenoids. In Chapter 1, a thorough biosynthetic relationship of DMOA-derived meroterpenoid subfamilies is reviewed and the most updated isolation and syntheses are covered with the purpose to provide the reader an understanding and appreciation of the origin of the exceptional diversity of DMOA-derived meroterpenoids. In Chapter 2, three generations of routes towards DMOA-derived spiromeroterpenoid are discussed in detail. The oxidative [3+2] cyclization approach was found to generate several complex dimers and the simplicission core. Lessons learned therein pointed to a successful strategy. In Chapter 3, a successful fragment coupling strategy culminated in a concise, modular, and collective synthesis of five spiromeroterpenoid natural products. The synthesis features a sterically hindered bis-neopentyl 1,2-addition coupling/oxidative Michael addition/MHAT reduction sequence to rapidly construct the conserved spirocycle with full stereo-control. The gateway natural product asnovolin A was secured in deca-milligram amounts which laid the foundation for chemoenzymatic synthesis of the highly oxidized spiromeroterpenoid novofumigatonin. In Chapter 4, significant progress was made towards the synthesis of the complex meroterpenoid andiconin. We developed a late stage de novo construction of the dearomatized biosynthetic precursor. A biomimetic radical fragmentation [4+2] cascade was designed to establish the highly congested [2.2.2] octane core of the natural product. / 2026-03-15T00:00:00Z