Quinoline alkaloids: Synthesis of pyrano[2,3-b]quinolines, khaplofoline, lunacrine, and demethoxylunacrine

Polyphosphoric acid (PPA)-catalyzed cyclization of 2-ono-3-vinylquinolinecarboxylic acid (1) yielded 3,4-dihydro-2,2-dimethyl-2H-pyrano[2,3-b]quinoline (4). The same reaction of 4-methoxy-2-oxo-3-vinylquinolinecarboxylic acid (1g) afforded 4-methoxy-2,2-dimethylpyrano[2,3-b]quinoline (4g), which on hydrolysis with ethanolic hydrochloric acid gave khaplofoline (5). The Prevost reaction of 4-methoxy-3-prenylquinolin-2-one (6) using I-2/HgO in acetic acid yielded 4-methoxy-2-isopropyIfuro[2,3-b]quinoline (7). Compound 7 on reduction with H-2/Pd-C followed by N-methylation and de-O-methylation afforded lunacrine (10a). A similar reaction sequence on 6b gave demethoxylunacrine (10b).