Collect. Czech. Chem. Commun. 1996, 61, 478-488

2',3'-Dideoxy- and 3'-Azido-2',3'-dideoxynucleosides of 5-Phenyl-2(1H)-pyrimidinone. Preparation of 2',3'-Dideoxypentofuranoses

Marcela Krečmerová, Hubert Hřebabecký, Milena Masojídková and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic


The synthesis of methyl 3-azido-5-benzoyl-2,3-dideoxy-β-D-ribofuranoside (10) from methyl 2-deoxy-D-ribofuranoside (1) and its use for the preparation of 3'-azido-2',3'-dideoxy-β-D-ribofuranosides is described. Reaction of methylglucoside 1 with benzoyl chloride in pyridine afforded 5-O-benzoyl derivative 2, which on oxidation with complex of chromium trioxide, pyridine and acetic anhydride afforded 3-keto derivative 3. This was reduced with sodium borohydride in ethanol to give a mixture of methyl 2-deoxyglycosides of α-D-ribo- (4) and β-D-xylo- (5) configuration. Their mesyl derivatives 6 and 7 were chromatographically separated. Compound 7 reacted with sodium azide in hot dimethylformamide to afford methyl 3-azido-5-O-benzoyl-2,3-dideoxy-β-D-ribofuranoside (10). 5-Phenyl-2(1H)-pyrimidinone was converted into silyl derivative 11 by treatment with hexamethyldisilazane. Reaction of compound 11 with the azido sugar 10, catalyzed by trimethylsilyl trifluoromethanesulfonate, and subsequent methanolysis, furnished a mixture of anomeric 3'-azido-2',3'-dideoxynucleosides 14 and 15. Methyl 5-O-benzoyl-2,3-dideoxy-α-D-ribofuranoside (17) was prepared from methyl-α-glycoside 4 by reaction with thionyl chloride and subsequent reduction of the obtained 3-chloro derivative 16 with tributylstannane. Silyl derivative 11 reacted with 2,3-dideoxy sugar 17 under catalysis with trimethylsilyl triflate to give mainly 1-(5-O-benzoyl-2,3-dideoxy-α-D-glycero-pentofuranosyl)-5-phenyl-2(1H)-pyrimidinone (19) and minor amount of the β-anomer 18. Their methanolysis afforded dideoxynucleosides 20 and 21.

Keywords: Nucleosides; Pyrimidine; Sugar-modified; AZT analogs; Dideoxynucleosides; 5-Phenyl-2(1H)-pyrimidinone.