SYNTHESIS OF 2,6-DIOXO-(1H,3H)-9-N-RIBITYLPURINE AND 2,6-DIOXO-(1H,3H)-8-AZA-9-N-RIBITYLPURINE AS INHIBITORS OF LUMAZINE SYNTHASE AND RIBOFLAVIN SYNTHASE

2,6-Dioxo-(1H,3H)-9-N-ribitylpurine (6) and 2,6-dioxo-(1H,3H)-8-aza-9- N-ribitylpurin (7) have been synthesized and evaluated as inhibitors o f lumazine synthase and riboflavin synthase. Reaction of 5-amino-6-rib ityl-aminouracil hydrochloride (8) with diethoxymethyl acetate (9) aff orded the purine 6, while diazotization of 8 afforded the 8-aza purine 7. Compounds 6 and 7 were evaluated against lumazine synthase of Baci llus subtilis and riboflavin synthase of Escherichia coli. Both 6 and 7 were better inhibitors of lumazine synthase than riboflavin synthase . The 8-azapurine 7 had a lower K-I (0.33 and 0.39 mM) than the purine 6 (0.47 and 0.54 mM) when evaluated with lumazine synthase and ribofl avin synthase, respectively. (C) 1998 Elsevier Science Ltd. All rights reserved.