Synthesis of 5-Dialkylaminomethyl-3'-azido and 3'-Fluoro-2',3'-dideoxyuridines for Evaluation as Anti-HIV Agents

Article abstract of DOI:10.1007/BF00808509

Uracil (8) was substituted in a Mannich reaction to give the 5-substituted dialkylaminomethyluracils 11a-f in 65-85percent yield.Compounds 11a-f were silylated with hexamethyldisilazane and coupled with 2,3-dideoxy-3-fluoro-D-erythro-pentofuranoside 4 and 3-azido-2,3-dideoxy-D-erythro-pentofuranoside 7 to give the corresponding 3'-fluoro-2',3'-didoeoxynucleosides 13a-f and 3'-azido-2',3'-dideoxy nucleosides 16d,f, respectively, by using trimethylsilyl trifluoromethanesulfonate as a catalyst.Deprotection of the 5-O-(4-phenylbenzoyl) protected nucleosides 13a-f and 16d,f with saturated methanolic ammonia and separation by chromatography yielded the new derivatives of 2',3'-dideoxy-3'-fluorouridines 14a-f and 15a-f and 2',3'-dideoxy-3'-azidouridines 17d,f and 18d,f. Keywords: Nucleosides, convergent synthesis of; Uridines, 3'-azido-2',3'-dideoxy; Uridines, 3'-fluoro-2',3'-dideoxy; AZT analogues; Human immunodeficiency virus; Herpes simplex virus.