Synthesis of all monofluoro 4'-thio-2',3'-dideoxypyrimidine nucleosides was achieved and the structures of the products confirmed by X-ray analysis. A novel mechanism of fluorination with diethylaminosulfur trifluoride T) that proceeded with overall retention of configuration was discovered and applied to the synthesis of these compounds. A new improved method for the synthesis of the sugar moiety of 9-(2,3- dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (FddA) - a DN- approved compound - was refined and optimized. This method should reduce cost of production of FddA. A patent application was filed. Selected acid-stable 6X-substituted-(2'-fluoro-2',3'-dideoxy-beta-D-threo- pentofuranosyl)purines (X = F, Cl, Br, I, OMe, OEt, NHMe, NMe2, NHEt, NHNH2, NHOH, NHOMe, NHOCH2Ph, NO2) were synthesized as anti-HIV adenosine deaminase-activated """"""""pro drugs"""""""" for F-ddI. These compounds should have favorable biological transport properties prior to enzymatic conversion to their anti-HIV-active parent compound.
