SYNTHESIS OF ANTITUMOR/VIRAL PYRIMIDINE C NUCLEOSIDES

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Chemical methods will be developed for the preparation of six classes of C-nucleosides which are close analogs of either naturally-occurring nucleosides or synthetic nucleosides with established antitumor and/or antiviral activity. New ring transformation reactions will be developed and applied to facile synthesis of antitumor antibiotics, showdomycin and oxazinomycin, and their analogs (Classes 1 and 2) from Psi-uridine. C-Nucleoside analogs (Classes 3 and 4) of thymidine and 2'-deoxycytidine will be synthesized from Psi-uridine by application of our recently developed pyrimidine to pyridine ring transformation reaction. C-Nucleoside analogs (Classes 5 and 6) of the potent antiherpetic and potential antileukemic agent, FMAU, will be synthesized either by modification of a preformed C-nucleoside (Psi-uridine) at the sugar moiety, or from an appropriate 2-fluoro-arabino-furanose derivative by total synthesis. "In house" biochemical and chemotherapeutic collaborative studies for proper evaluation of the targeted C-nucleosides are described briefly. From these studies, structure-activity relationships should be forthcoming to aid in the development of new agents superior to those currently available for the treatment of cancer and/or viral infection in man.