Conversion of some pyrimidine 2′-deoxyribonucleosides into the corresponding 2′,3′-didehydro-2′,3′-dideoxynucleosides

Abstract

Thymidine 4b was converted into 2,3′-anhydro-1-(2′-deoxy-β-D-threo-pentofuranosyl)thymine 7b in ∼65% isolated yield by being heated at 155 °C with an excess of diphenyl sulfite and 1-methylimidazole in N,N-dimethylacetamide solution. 2′-Deoxyuridine 4a, 2′-deoxy-5-ethyluridine 4c and 2′-deoxy-5-fluorouridine 4d were similarly converted into 2,3′-anhydronucleosides which were isolated as their 5′-O-(tert-butyldimethylsilyl) derivatives 8a, 8c and 8d in 51, 50 and 59% yield, respectively. When the oxetane derivatives 5a–d, prepared by the literature procedure from the parent 2′-deoxynucleosides 4a–d, were heated with an excess of sodium hydride in N,N-dimethylacetamide solution at 100 °C, they were converted into the corresponding 2′,3′-didehydro-2′,3′-dideoxynucleo-sides 6a–d in 68, 76, 69 and 74% isolated yield, respectively. The latter compounds were similarly prepared from the 2,3′-anhydronucleosides 7a–d in 71, 81, 69 and 74% isolated yield, respectively. 2,3′-Anhydro-5′-O-(tert-butyldimethylsilyl)-2′-deoxy-5-(trifluorornethyl)- and -5-iodo-1 -(β-D-threo-pentofuranosyl)uracil 8e and 8f, which were themselves prepared from the parent 2′-deoxynucleosides 4e and 4f, respectively, in ∼60 and 50% yield, were converted by a three-step procedure via the intermediate 2′-deoxy-3′-(phenylseleno) derivatives 10e and 10f into the corresponding 2′,3′-didehydro-2′,3′-dideoxynucleosides 6e and 6f in 52 and 49% overall yield, respectively. Compound 8e was also converted into 2′,3′-dideoxy-5-(trifluoromethyl)uridine 11b and 3′-azido-2′,3′-dideoxy-5-(trifluoromethyl)uridine 11c in 49 and 66% overall yield, respectively.