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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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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Antineoplastic Agents
Hydrobromic Acid
Naphthyridines
Cells
Derivatives
Signal transduction
Cell growth
Microorganisms
X rays
4-methylaaptamine
9-demethylaaptamine
isoaaptamine
aaptamine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Antineoplastic Agents 491.1 Synthetic Conversion of Aaptamine to Isoaaptamine, 9-Demethylaaptamine, and 4-Methylaaptamine. / Pettit, George; Hoffmann, Holger; Herald, Delbert L.; McNulty, James; Murphy, Alison; Higgs, Kerianne C.; Hamel, Ernest; Lewin, Nancy E.; Pearce, Larry V.; Blumberg, Peter M.; Pettit, Robin; Knight, John C.

In: Journal of Organic Chemistry, Vol. 69, No. 7, 02.04.2004, p. 2251-2256.

Research output: Contribution to journalArticle

Pettit, G, Hoffmann, H, Herald, DL, McNulty, J, Murphy, A, Higgs, KC, Hamel, E, Lewin, NE, Pearce, LV, Blumberg, PM, Pettit, R & Knight, JC 2004, 'Antineoplastic Agents 491.1 Synthetic Conversion of Aaptamine to Isoaaptamine, 9-Demethylaaptamine, and 4-Methylaaptamine', Journal of Organic Chemistry, vol. 69, no. 7, pp. 2251-2256. https://doi.org/10.1021/jo0300486
Pettit, George ; Hoffmann, Holger ; Herald, Delbert L. ; McNulty, James ; Murphy, Alison ; Higgs, Kerianne C. ; Hamel, Ernest ; Lewin, Nancy E. ; Pearce, Larry V. ; Blumberg, Peter M. ; Pettit, Robin ; Knight, John C. / Antineoplastic Agents 491.1 Synthetic Conversion of Aaptamine to Isoaaptamine, 9-Demethylaaptamine, and 4-Methylaaptamine. In: Journal of Organic Chemistry. 2004 ; Vol. 69, No. 7. pp. 2251-2256.
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