Preparation of 2'-deoxyribonucleosides and their 5-halogeno derivatives

Abstract

Two routes are described for the synthesis of 2'-deoxyribonucleosides from ribonucleosides. The reaction of uridine (Ia) with acetyl bromide affords the acetylated 2'-bromo derivative IIIe (73%) and triacetyluridine (Ib; 7%). The tributyltin hydride reduction of the reaction mixture yields diacetyl-2'-deoxyuridine (IIIc; 71%) along with triacetyluridine (Ib; 8%). On reaction of 5-fluorouridine (Ic) with acetyl bromide, the triacetyl-5-fluorouridine (Id; 39%) and the diacetyl-2'-bromo derivative IIIg are obtained. The tributyltin hydride reduction of IIIg affords diacetyl-2'-deoxy-5-fluorouridine (IIIh; 47.5%, referred to Ic). The reaction of cyclouridine (IIa) with acetyl chloride and the subsequent tributyltin hydride reduction followed by methanolysis furnishes 2'-deoxyuridine (IIId; 88.5%, referred to IIa). Diphenyl carbonate (IV) is prepared by reaction of phosgene with phenol in pyridine. On reaction with N-bromosuccinimide, diacetyl-2'-deoxyuridine (IIIc) (2'-deoxyuridine IIId, resp.) affords di-O-acetyl-5-bromo-2'-deoxyuridine (IIIj; 78%) (5-bromo-2'-deoxyuridine IIIk; 43%, resp.).