Regiospecific formation of 9,3-propeno-8-aza-9H-xanthines and their conversion into 3-(2,3-dihydroxypropyl)-8-aza-9H-xanthine and derivatives

Abstract

A novel series of C-11-functionalized 3,9-propano-8-aza-9H-xanthine and related compounds have been synthesized. With 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 11-methylsulphonyloxy-3,9-propano-8-aza-9H-xanthine (11) underwent a regiospecific elimination to give 9,3-propeno-8-aza-9H-xanthine (19). An equally interesting result was obtained from (19) on osmium tetraoxide oxidation, when 10,11-dihydroxy-3,9-propano-8-aza-9H-xanthine (20) was formed and then transformed into 3-(2,3-dihydroxypropyl)-8-aza-9H-xanthine (22) by aqueous NaBH₄ treatment. Reaction of compound (19) with bromine in methanol afforded 11-bromo-10-methoxy-3,9-propano-8-aza-9H-xanthine (28). The latter on stereochemically controlled elimination with DBU led to 10-methoxy-3,9-propeno-8-aza-9H-xanthine (29), easily converted into 11-bromo-10,12-dimethoxy-3,9-propano-8-aza-9H-xanthine (30).