SYNTHESIS OF MESOIONIC NUCLEOSIDES AS ANTINEOPLASTIC AND ANTIMICROBIAL AGENTS

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A novel series of mesoionic xanthine-based acyclonucleosides will be synthesized, characterized and investigated as potential antiprotozoan agents in vitro and in vivo and as potential antitumor agents in vitro. The nucleoside analogues, by modification of the activity of the enzymes of nucleic acid biosynthesis, provide some of the most powerful and useful inhibitors of viral replication and neoplastic tissue growth. Fertile though the nucleoside field has been, most of the existing antibiotic purine and pyrimidine nucleosides are associated with serious toxicity. In addition, resistance to them is becoming an increasing problem. Intensive efforts to find structurally-related more selective and effective therapeutic alternatives have been underway in various laboratories in the past decade and it remains an unmet need of antiviral and cancer chemotherapy in the 1990s. Although a number of mesoionic xanthine nucleoside analogues with modifications being made in the heterocyclic base and/or the sugar moiety have been previously investigated for their antiviral or cytostatic activities, mesoionic derivatives containing acyclic carbohydrate moiety as proposed in the present study, have not been described. The mesoionic compounds will be prepared by cyclocondensation of appropriate protected glycoside precursors with malonic ester, substituted malonic esters or chlorocarbonylphenyl ketene followed by deprotection with dimethylamine. The synthesized compounds will be characterized spectroscopically by proton magnetic resonance (1 H NMR), carbon-13 magnetic resonance (13C NMR), mass spectrometry (MS), ultraviolet spectroscopy (UV), infrared spectroscopy (IR) and carbon, hydrogen, nitrogen elemental analysis.