Anthraquinone-xanthone heterodimeric natural products are a diverse family of polyketides highlighted by a unique bicyclo [3.2.2] ring system which links both anthraquinone and xanthone moieties. Both the connectivity of the unique bicyclic ring system and the oxidation state of the two heterocycles vary among the members of this family of natural products. These molecules have been generally isolated as fungal metabolites but also have shown anticoccidial (xanthoquinodin A:0.02 μg/mL), antibiotic (acremonidins A and C; 32 μM and acremoxanthone, MIC; 12.5 μg/mL), and cytotoxicity against various human cancer cell lines. Both anthraquinone and xanthone heterocycles are derived from the anthraquinone chrysophanol, a common biosynthetic intermediate for polyketide synthesis. To date, there have been no reported synthetic efforts or total syntheses of the anthraquinone-xanthone heterodimeric natural products. Related synthetic examples include complex anthraquinone-xanthone biaryls, anthraquinone dimers, and monomeric xanthone and benzophenone-derived natural products.
We describe an initial proposed synthesis wherein we aimed to prepare the unique bicyclo [3.2.2] ring system in a late stage operation of functionalized anthraquinone and xanthone units through a photo-mediated cycloaddition. We achieved synthesis of both an anthraquinone-derived oxanthrone ester fragment and the synthesis of several xanthone related natural products, namely graphisin A, sydowinin B, acremonidin E, and pinselin. Key steps involve aryl anion addition to substituted benzaldehyde derivatives, subsequent methyl ester installation, and dehydrative cyclization. Although we have not yet achieved the desired cycloaddition, we contributed to this area by developing efficient, reliable syntheses of various benzophenone and xanthone natural products.
We will also describe an alternative strategy to access the bicyclo [3.2.2] core of these natural products via various proposed rearrangements of an anthraquinone-xanthone biaryl intermediate. Cross-coupling of substituted xanthone and naphthalene fragments established the desired biaryl linkage which was further elaborated to afford anthraquinone-xanthone biaryl structures. Attempts to rearrange these biaryls are ongoing to produce the unique core structure of the parent natural products.
Initially discovered as a byproduct of the aforementioned cross-coupling reaction, we have achieved homo-coupling of substituted naphthalene fragments. The resulting naphthalene dimers could be further advanced to a series of novel 2,2'-linked anthraquinone dimers including the natural product chrysotalunin.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/14140 |
| Date | 22 January 2016 |
| Creators | Little, Andrew John |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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