3,5-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. / 2023-09-10T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/42996 |
| Date | 10 September 2021 |
| Creators | Powers, Zachary |
| Contributors | Porco, Jr., John A. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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