As part of a previous neurotoxicity study, naturally-occurring annonacin was isolated and purified from North American pawpaw (Asimina triloba) fruit pulp according to earlier reports from these laboratories. The natural product was submitted to the rat aortic ring assay (RAR) for evaluation of antiangiogenic activity and was found active in the 3µM range. The alcohol groups of annonacin were submitted to permesylation followed by azide displacement which gave the 4,10,15,20-tetradeoxy-4,10,15,20-tetraazidoanonnacin. Presumably, the permesylate gave the azide groups in the opposite configuration as the hydroxyl groups in annonacin while iodination of the alcohol groups followed by azide displacement gave all the azide groups in the same configuration as the hydroxyls in the natural product. The membrane permeability of annonacin was also measured using a PAMPA assay, and despite its lipid-like properties, was found to have relatively low permeability. The synthesis of the tetraazides, their click reactions and RAR assay results of all compounds will be discussed.

Antiangiogenic activity and chemical derivatization of the neurotoxic acetogenin, annonacin isolated from Asimina triloba

256th National Meeting (2018)

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