Chalaniline B [2,8-dihydroxy-3-(hydroxymethyl)-1-(phenyl)aminoxanthone, CB] was identified by Loesgen and coworkers from an antimicrobial-bioassay guided fractionation of a culture of the endophytic ascomycete Chalara sp. 6661 that had been treated with the HDAC inhibitor vorinostat. In addition to activating the genes necessary to elicit production of xanthone CB, the epigenetic perturbation agent vorinostat was itself biotransformed and discovered to be the source of the anilino moiety found both within CB and another unusual xanthone (chalaniline A) that was also isolated. 1-Arylaminoxanthones represent a new chemotype and this fact, taken together with preliminary findings indicating that CB has moderate antimicrobial activity against a multidrug resistant S. aureus strain (ATCC BAA-44), prompted us to pursue a chemical synthesis. The development of a successful elaboration of CB from 2-hydroxyxanthone by a route incorporating strategic oxidations followed by regioselective introduction of nitrogen- and carbon-based moieties to the resulting 1,3-dibromo-2,8-dihydroxyxanthone derivative, will be presented and contrasted against alternate, and perhaps more obvious, approaches that failed. It is anticipated that the lessons learned from the total synthesis of CB will prove useful in the pursuit of analogous compounds for SAR and mode-of-action studies that may lead to the identification of antibiotics with heightened potency.

Total synthesis of chalaniline B: Antibiotic xanthone from epigenetically-treated endophytic fungus Chalara

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.