Porco, Jr., John A.Powers, Zachary2021-09-132021https://hdl.handle.net/2144/429963,5-Dimethylorsellinic acid (DMOA)-derived meroterpenoids are a rich, structurally diverse family of natural products with a range of biological activities. Several total syntheses have been completed to date, but no broad synthetic scheme has been developed. In order to address this problem, a synthetic platform to produce 3,5-dimethylorsellinic acid (DMOA) meroterpenoids has been developed. Using a biomimetic strategy, DMOA was directly coupled to farnesyl electrophiles using a regioselective, base-mediated alkylative dearomatization strategy. Further chemical reactions including methylation and polyene cyclization resulted in the production of five unique tetracyclic DMOA-derived meroterpenoids. An understanding of the stereochemical outcome was explained via computational and experimental methods. Further development of the platform involved incubation of synthetic farnesyl-DMOA coupling substrates with terpene cyclase enzymes in a collaborative effort to produce novel chemoenzymatic DMOA-derived meroterpenoids. DMOA and DMOA methyl ester were employed in this strategy with multiple farnesyl derivatives to create both natural and non-natural DMOA-derived products. After both chemical and chemoenzymatic studies were completed, additional studies were initiated to synthesize the specific meroterpenoid target asperterpene A, an inhibitor of the B-secretase (BACE1) enzyme. A strategy involving direct alkylation of the decalin core using DMOA will be described, as well as a synthetic strategy from (-)-carvone.en-USOrganic chemistryThesis/Dissertation2021-09-10