Antineoplastic Agents 491.1Synthetic Conversion of Aaptamine to Isoaaptamine, 9-Demethylaaptamine, and 4-Methylaaptamine⊥ Academic Article uri icon

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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.

authors

  • Pettit, George R
  • 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 K
  • Knight, John C

publication date

  • April 2004