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Abstract

Reaction of 3,4,6-tri-O-acetyl-2-deoxyglucopyranosyl bromide (1) with silylated 5-benzyluracil and subsequent ammonolysis afforded α- and β-anomers of 5-benzyl-1-(2-deoxy-D-glucopyranosyl)uracil (2 and 3). Under catalysis with tin tetrachloride, silylated 5-benzyluracil reacted with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose to give 2',3',5'-tri-O-benzoyl-5-benzyluridine (10), which was converted into the 4-thio derivative 11 by reaction with Lawesson reagent. Debenzoylation of compound 11 afforded 5-benzyl-4-thiouridine (12), whereas its reaction with methyl iodide and deblocking gave 4-methylthiopyrimidine nucleoside 14. Amonolysis of derivative 12 at elevated temperature afforded 5-benzylcytidine (15). This reacted with thionyl chloride at room temperature to give cyclic sulfite 16 which on heating at 100 °C in dimethylformamide was converted into 5-benzyl-2,2'-cyclocytidine (17). Mild alkaline hydrolysis of compound 17 afforded 1-(β-D-arabinofuranosyl)-5-benzylcytosine (18). With boiling thionyl chloride, compound 15 formed 2',3'-cyclic sulfite 19 which on alkaline hydrolysis gave 5-benzyl-5'-chloro-5'-deoxycytidine (20). Compound 20 was reduced with tributylstannane to 5-benzyl-5'-deoxycytidine (21). Reaction of silylated 5-benzyluracil with 2-deoxy-3,5-bis(O-p-toluoyl)-D-ribofuranosyl chloride, catalyzed with mercury(II) bromide, afforded 5-benzyl-2'-deoxy-3',5'-bis(O-p-toluoyl)uridine (22) and its α-anomer 23. With Lawesson reagent, compound 22 gave 5-benzyl-4-thiouracil derivative 24 which was ammonolyzed to give 5-benzyl-2'-deoxycytidine (25). Analogously, compound 23 was converted into 5-benzyl-2-deoxy-α-cytidine (27). 5'-O-Benzoyl-5-benzyluridine (29) was converted into the 2,2'-anhydro derivative 30 which on reaction with hydrogen chloride afforded 3'-chloro-3'-deoxynucleoside 31. This compound was reduced with tributylstannane and the obtained 2'-deoxynucleoside 32 on treatment with thionyl chloride gave a mixture of erythro- and threo-3'-chloro-2',3'-dideoxynucleosides (33 and 34, respectively) which were reduced to 5'-O-benzoyl-5-benzyl-2',3'-dideoxyuridine (35). Compound 35 reacted with Lawesson reagent under formation of 4-thiouracil derivative 36 and this was deblocked to 5-benzyl-4-thio-2',3'-dideoxyuridine (37). On heating with ammonia, compound 37 was converted into 5-benzyl-2',3'-dideoxycytidine (38). Reaction of 4-thiouracil derivative with methyl iodide and subsequent hydrazinolysis afforded 4-hydrazino derivative 40 which was heated with silver oxide in ethanol to give a mixture of anomeric 5-benzyl-1-(2,3-dideoxyribofuranosyl)-2(1H)-pyrimidinones (42).

Keywords: 5-Benzyluracil; Pyrimidine; Nucleosides; Uridine phosphorylase.