Synthesis of 2',3'-Dideoxynucleosides from 5-Alkoxymethyluracils

Article abstract of DOI:10.1007/BF00815166

A modified synthesis of protected 2,3-dideoxyribose 5 starting from L-glutamic acid (1) is described.Reaction of 5 with silylated 5-hydroxymethyluracil 7a and 5-alkoxymethyluracils 7b-e in the presence of trimethylsilyl triflate afforded an anomeric mixture of 2',3'-dideoxyuridine derivatives 8a-e and 9a-e.Deprotection with methanolic ammonia and separation by chromatography gave the corresponding nucleosides 10a-e and 11a-e.Treatment of 9b-e with tri(1H-1,2,4-triazol-1-yl)phosphine oxide and subsequent reaction of 12b-e with ammonia in dioxane afforded the cytosine derivatives 13b-e which on treatment with methanolic ammonia gave the corresponding 2',3'-dideoxycytidine derivatives 14b-e and 15b-e.In contrast with the parent compounds, these alkoxymethyl derivatives had no appreciable activity against human immunodeficiency virus (HIV-1).