Synthesis of 1-(3-Azido-2,3-dideoxy-β-D-ribo-hexofuranosyl)-, 1-(2,3-Dideoxy-β-D-erythro-hexofuranosyl)- and 1-(2,3-Dideoxy-β-D-erythro-hex-2-enofuranosyl)pyrimidine Nucleosides

Abstract

1-(3-Azido-2,3-dideoxy-β-D-ribo-hexofuranosyl)uracil (XXII) and 1-(2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)uracil (VIII) were prepared starting from 1-(2-O-acetyl-3,5,6-tri-O-benzoyl-β-D-glucofuranosyl)uracil (I) by a procedure described previously for thymine analogs. 1-(2,3-Dideoxy-β-D-erythro-hexofuranosyl)uracil (XIII) was obtained by catalytic hydrogenation of 1-(5,6-di-O-benzoyl-2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)uracil (VII) and subsequent methanolysis. Reaction of dibenzoyl derivative VII, 1-(5,6-di-O-benzoyl-2,3-dideoxy-β-D-erythro-hexofuranosyl)uracil (XII) and the diacetate prepared by acetylation of azido derivative XXII with Lawesson's reagent, followed by methanolysis, afforded 1-(2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)-4-thiouracil (X), 1-(2,3-dideoxy-β-D-erythro-hexofuranosyl)-4-thiouracil (XV) and 1-(3-azido-2,3-dideoxy-β-D-ribo-hexofuranosyl)-4-thiouracil (XXIII), respectively. Heating of thio derivatives X, XV and XXIII with methanolic ammonia at 100 °C gave 1-(2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)cytosine (XI), 1-(2,3-dideoxy-β-D-erythro-hexofuranosyl)cytosine (XVI) and 1-(3-azido-2,3-dideoxy-β-D-ribo-hexofuranosyl)cytosine (XXIV).