The tree and shrub species belonging to the Myrtaceae family are rich in structurally diverse meroterpenoids which possess anti-cancer, anti-malarial, anti-bacterial, anti-viral, and anti-inflammatory biological activities. Many of the natural products belonging to this family are derived from two common precursors: syncarpic acid and formyl phloroglucinol. The dissertation research described herein is focused on the total synthesis of two subclasses of natural products: syncarpic acid-derived meroterpenoids and formyl phloroglucinol meroterpenoids. The synthetic methodologies disclosed were developed to enrich the chemodiversity of these novel meroterpenoids by providing efficient access to such scaffolds and derivatives. Rhodomyrtusials A–C, the first examples of syncarpic acid-derived sesquiterpene meroterpenoids featuring a unique 6/5/5/9/4 fused pentacyclic ring system, were isolated from Rhodomyrtus tomentosa along with several biogenetically-related dihydropyran isomers. Two bis-furans and one dihydropyran isomer showed acetylcholinesterase (AChE) inhibitory activity. Herein, the bioinspired total syntheses of six isolates were achieved in six steps utilizing a reactive enetrione intermediate generated in situ from a readily available hydroxy-endoperoxide precursor are reported. Further evaluation of alkene reaction partners identified additional modes of reactivity for the enetrione, leading to the production of novel small molecule scaffolds. Furthermore, computational studies have identified a valid asynchronous, concerted pathway leading to the formation of the bis-furan containing natural products. Eucalyptusdimers A−C, three dimeric phellandrene-derived formyl phloroglucinol meroterpenoids featuring an unprecedented, fused skeleton between two phellandrene and two acylphloroglucinol subunits, along with one biogenetically related intermediate eucalyprobusone A, were isolated from the fruits of Eucalyptus robusta. These isolates also showed AChE inhibitory activity. A one-pot, three-component reaction was identified to achieve the synthesis of eucalyprobusone A and subsequent synthetic efforts towards eucalyptusdimers A and B via hetero-Diels Alder (HDA) [4+2] cycloaddition with known terpene, alpha-phellandrene are outlined. Initial efforts failed to promote the desired HDA cycloaddition, which led to alternate exploration of oxidative [4+2] cycloaddition chemistry. Using this revised strategy, the synthesis of several Eucalyptus metabolites including grandinol, euglobal IIc, and euglobal T1 was achieved. Future efforts and synthetic strategies to afford the eucalyptusdimers from these precursors are provided. / 2025-09-20T00:00:00Z