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Abstract

Reaction of silylated 5-phenylcytosine with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribose, catalyzed with tin tetrachloride, and subsequent methanolysis afforded 5-phenylcytidine (2). This compound reacted with thionyl chloride in acetonitrile to give cyclic sulfite 3 which on heating in dimethylformamide was converted into 2,2'-anhydro-1-(β-D-arabinofuranosyl)-5-phenylcytosine (4). Analogous reaction of compound 2 with thionyl chloride at reflux gave 5'-chloro-5'-deoxy-2',3'-cyclic sulfite 5. Its heating in dimethylformamide afforded 5'-chloro-2,2'-anhydro derivative 6, mild alkaline hydrolysis led to 5'-chloro-5'-deoxy-5-phenylcytidine (7). Alkaline hydrolysis of 5-phenyl-2,2'-anhydrocytidine (4) gave 5-phenylcytosine arabinoside 8, whereas the 2,2'-anhydro derivative 6 afforded 1-(5-chloro-5-deoxy-β-D-arabinofuranosyl)-5-phenylcytosine (11). At higher temperature, the final reaction product was 2,5'-anhydro-5-phenylcytidine (12). 5'-Chloro-5'-deoxynucleosides 7 and 11 reacted with tri-n-butyl- stannane to give 5'-deoxyribofuranosyl and 5'-deoxyarabinofuranosyl derivatives 15 and 16. 5-Phenylcytidine (2) was converted into the N⁴-acetate 17 with acetic anhydride. Further reaction with acetic anhydride and hydrogen bromide in acetic acid afforded a mixture of peracetylated 2'-bromo and 3'-bromo derivatives 18 and 19. Reaction with Zn/Cu couple gave 5'-O-acetyl-5-phenyl-2',3'-didehydro derivative 20 and 2',3',5'-tri-O-acetyl-5-phenylcytidine (21). Compound 20 was deblocked to 1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-5-phenylcytosine (22). Catalytic hydrogenation of compound 20 over palladium and subsequent deblocking of the protected 2',3'-dideoxy derivative 23 gave 1-(2,3-dideoxy-β-D-glycero-pentofuranosyl)-5-phenylcytosine (24).

Keywords: 5-Phenylcytosine; Nucleosides; Pyrimidine; 2',3'-Dideoxynucleoside.