Synthesis of 1-functionalized-6-hydroxy-4-methyl and 6,11-dihydroxy-4-methylnaphtho[2,3-g]isoquinoline-5,12-quinones

Abstract

Using 2-methoxy- and 2,5-dimethoxyacetophenones 8a and 8b as starting materials, 1-chloro-4-methylisoquinoline-5,8-quinone (6) and its 6-bromo derivative 7 were obtained via multistep sequences. Whereas Diels-Alder condensation of the former compound with homophthalic anhydride (22) led to a mixture of the two possible isomers: 1-chloro-11-hydroxy-4-methylnaphtho[2,3-g]isoquinoline-5,12-quinone (23) and 1-chloro-6-hydroxy-4-methylnaphtho[2,3-g]isoquinoline-5,12-quinone (24), this last tetracyclic chloroquinone was specifically obtained from 6-bromo-1-chloro-4-methylisoquinoline-5,8-quinone (7) and homophthalic anhydride. The 6,11-dihydroxy derivative was then prepared by ammonium nitrate oxidation or photochemically by cycloaddition of benzocyclobutenedione (28) and 1-chloro-4-methylisoquinoline-5,8-quinone (6). Chloro compounds were easily substituted by diamines to provide corresponding 1-amino substituted hydroxy tetracyclic quinones.