SYNTHESES OF DIMENSIONALLY ALTERED ENZYME SUBSTRATES BY MEANS OF THE FINKELSTEIN REACTION (BENZOPURINE, NAPHTHOPURINE)

Methods for the synthesis of 9-aminobenzimidazo{5,6-g}quinazoline (lin-naphthoadenine) and 9-amino-3-(beta)-D-ribofuranosylbenzimidazo{5,6-g}quinazoline (lin-naphthoadenosine) have been developed. The synthetic route commenced with 5,6-dimethylbenzimidazole and the linear array of rings was constructed by means of the Finkelstein reaction. lin-Naphthoadenosine was synthesized by ribosidation of 9-methylthiobenzimidazo{5,6-g}quinazoline followed by ammonia displacement. Syntheses of benzimidazo{5,6-g}-8H-quinazolin-9-one (lin-naphthohypoxanthine) and benzimidazo{5,6-g}-6H,8H-quinazoline-7,9-dione (lin-naphthoxanthine) were accomplished by similar routes. lin-Naphthoadenine and lin-naphthoadenosine were both found to be highly fluorescent. Neither of these purine analogs was found to be a substrate when tested for activity with the enzyme adenosine deaminase from calf intestinal mucosa.;A synthetic route to imidazo{4,5-g}quinazolines (lin-benzopurines) reduced in the central ring has also been investigated. The first representative of this class of compounds, 4,7,8,9-tetrahydroimidazo{4,5-g}quinazoline-4,7-dione was synthesized from 1,3-diacetyl-4,5-dimethylimidazol-2-one in 5 steps utilizing the Finkelstein reaction to construct the tricyclic ring system.