Synthesis of 8-methoxy-1-methyl-1H-benzo[de][1,6]naphthyridin-9-ol (Isoaaptamine) and analogues.
8-Methoxy-1-methyl-1H-benzo[de][1,6]naphthyridin-9-ol, isoaaptamine, a PKC inhibitor isolated from sponge was synthesized. The synthesis parallels a synthesis of 8,9-dimethoxybenzo[de][1,6]naphthyridine, aaptamine, but uses a nitromethyl substituent as a precursor of the key 5-(2-aminoethyl)-1H-quinolin-4-one intermediate. The quinolone intermediates were prepared by thermolysis (220-240 degrees C) of anilinomethylene derivatives of Meldrum's acid. The quinolone intermediates were N-methylated prior to cyclization to the benzo[de][1,6]naphthyridine derivatives. Aaptamine and several analogues of aaptamine and isoaaptamine were prepared including 9-demethylaaptamine, 1-methyl-8-demethylaaptamine, 1-methylaaptamine, and the 8,9-methylenedioxy analogues of aaptamine and 1-methylaaptamine.
Walz
A J
AJ
Department of Chemistry, University of Virginia, McCormick Road, Charlottesville, Virginia 22904-4319, USA.
Sundberg
R J
RJ
D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D009287:Naphthyridines / Q000138:chemical synthesis*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D009287:Naphthyridines; C417553:isoaaptamine; D011493:Protein Kinase C