SYNTHESIS OF HYDANTOIN ANALOGS OF 3'-FLUORO-3'-DEOXYTHYMIDINE (FLT)

Reaction of methyl O-(4-phenylbenzoyl)-beta-D-erythro-pentofuranoside 2 with diethylaminosulfur trifluoride (DAST) in a 1:10 molar ratio in CH2Cl2 at room temperature for 5 d afforded methyl 2,3-dideoxy-3-fluor o-5-O-(4-phenylbenzoyl)-beta-D- erythro-pentofuranoside 4 in 57% yield , while the alpha-anomer 3 under the same reaction conditions yielded the 3-fluoro-alpha-D-erythro derivative 10 in 14% yield together with the 5-fluoro-alpha-D-threo derivative 11 in 22% yield. (Z)-5-Benzylide ne-, (E)-ethylidene- and 5,5-dimethylhydantoin nucleosides were obtain ed by condensation of the appropriate silylated nucleobases with 4 The protected nucleosides were in all cases deblocked by treatment with s odium methoxide in methanol. The (Z)-ethylidene group isomerized to th e E configuration during the nucleoside synthesis.