SYNTHESIS OF FURONAPHTH [1,3]OXAZINE AND FURO[1,3] OXAZINOQUINOLINE DERIVATIVES AS PRECURSORS FOR AN O-QUINONEMETHIDE STRUCTURE AND POTENTIAL ANTITUMOR AGENTS

The synthesis of dihydro furonaphth[1,3]oxazine derivatives 3 was perf ormed through a Mannich-type condensation between 2-cyano-5-hydroxy-3- methylnaphtho[1,2-b]furan 2a, 1.5 eq of a primary amine and 3eq of for maldehyde, Similarly, 2-cyano-5-hydroxy-3-methylfuro[2,3-f]quinoline 2 b gave the dihydro furo[1,3]oxazinoquinoline compounds 4, Heating a mi xture of the naphthofuran 2a, tert-butylamine and formaldehyde at tolu ene reflux led to the furonaphthoxazine 3e, which decomposes to afford an o-quinonemethide intermediate 5, The latter was trapped,vith 1-mor pholinopropene to give a dihydro furonaphthopyran derivative 6, All co mpounds 2, 3, 4 and 6 were assayed for in vitro cytotoxic activity tow ard L 1210, MDA-MB 231 and PC3 tumor cells, Among them, furonaphth[1,3 ]oxazines 3b, 3c, and furo[1,3]oxazinoquinolines 4c, 4d showed signifi cant activity against L 1210 cells, while furoquinoline 2b was the mos t cytotoxic compound towards all three cell lines.