Walz A J, Sundberg R J
Department of Chemistry, University of Virginia, McCormick Road, Charlottesville, Virginia 22904-4319, USA.
J Org Chem. 2000 Nov 17;65(23):8001-10. doi: 10.1021/jo001080s.
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.
8-甲氧基-1-甲基-1H-苯并[de][1,6]萘啶-9-醇、异aaptamine，一种从海绵中分离出的蛋白激酶C（PKC）抑制剂被合成出来。该合成方法与8,9-二甲氧基苯并[de][1,6]萘啶（aaptamine）的合成方法类似，但使用硝甲基取代基作为关键的5-(2-氨基乙基)-1H-喹啉-4-酮中间体的前体。喹诺酮中间体通过丙二酸亚异丙酯的苯胺基亚甲基衍生物的热解（220-240℃）制备。喹诺酮中间体在环化生成苯并[de][1,6]萘啶衍生物之前进行N-甲基化。制备了aaptamine以及aaptamine和异aaptamine的几种类似物，包括9-去甲基aaptamine、1-甲基-8-去甲基aaptamine、1-甲基aaptamine，以及aaptamine和1-甲基aaptamine的8,9-亚甲二氧基类似物。
