Antineoplastic Agents 491.1 Synthetic Conversion of Aaptamine to Isoaaptamine, 9-Demethylaaptamine, and 4-Methylaaptamine

George Pettit, Holger Hoffmann, Delbert L. Herald, James McNulty, Alison Murphy, Kerianne C. Higgs, Ernest Hamel, Nancy E. Lewin, Larry V. Pearce, Peter M. Blumberg, Robin Pettit, John C. Knight

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Abstract

Aaptamine (1) was used as starting material for synthetic transformation to isoaaptamine (2), 9-demethylaaptamine (5), and 4-methylaaptamine (6). A general method for the selective O-demethylation of such 1H-benzo [de] [1,6]-naphthyridine (1) marine sponge constituents at position C-9 has been developed. Selective O-demethylation of aaptamine (1) and 1-methylaaptamine (11) with 48% hydrobromic acid led to 9-demethylaaptamine (5) and isoaaptamine (2), respectively. A selection of other aaptamine derivatives were synthesized, and their structures were unambiguously determined by X-ray methods. In addition, their cancer cell growth inhibitory properties were evaluated against the murine P388 lymphocytic cell line and a minipanel of human cancer cell lines. Evaluation as inhibitors of the PKC signal transduction pathway and against a selection of microorganisms was also undertaken. Aaptamine derivatives 3 and 5 had broad-spectrum antimicrobial activities.

Original languageEnglish (US)
Pages (from-to)2251-2256
Number of pages6
JournalJournal of Organic Chemistry
Volume69
Issue number7
DOIs
StatePublished - Apr 2 2004

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ASJC Scopus subject areas

  • Organic Chemistry

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Pettit, G., Hoffmann, H., Herald, D. L., McNulty, J., Murphy, A., Higgs, K. C., Hamel, E., Lewin, N. E., Pearce, L. V., Blumberg, P. M., Pettit, R., & Knight, J. C. (2004). Antineoplastic Agents 491.1 Synthetic Conversion of Aaptamine to Isoaaptamine, 9-Demethylaaptamine, and 4-Methylaaptamine. Journal of Organic Chemistry, 69(7), 2251-2256. https://doi.org/10.1021/jo0300486