SYNTHESIS OF 5-PHENYLCYTOSINE NUCLEOSIDE DERIVATIVES

Reaction of silylated 5-phenylcytosine with 1-O-acetyl-2,3,5-tri-O-ben zoyl-D-ribose, catalyzed with tin tetrachloride, and subsequent methan olysis afforded 5-phenylcytidine (2). This compound reacted with thion yl chloride in acetonitrile to give cyclic sulfite 3 which on heating in dimethylformamide was converted into hydro-1-(beta-D-arabinofuranos yl)-5-phenylcytosine (4). Analogous reaction of compound 2 with thiony l chloride at reflux gave 5'-chloro-5'-deoxy-2',3'-cyclic sulfite 5. I ts heating in dimethylformamide afforded 5'-chloro-2,2'-anhydro deriva tive 6, mild alkaline hydrolysis led to 5'-chloro-5'-deoxy-5-phenylcyt idine (7). Alkaline hydrolysis of 5-phenyl-2,2'-anhydrocytidine (4) ga ve 5-phenylcytosine arabinoside 8, whereas the 2,2'-anhydro derivative 6 afforded -5-deoxy-beta-D-arabinofuranosyl)-5-phenylcytosine (11). A t higher temperature, the final reaction product was 2,5'-anhydro-5-ph enylcytidine (12). 5'-Chloro-5'-deoxynucleosides 7 and 11 reacted with tri-n-butylstannane to give 5'-deoxyribofuranosyl and 5'-deoxyarabino furanosyl derivatives 15 and 16. 5-Phenylcytidine (2) was converted in to the N-4-acetate 17 with acetic anhydride. Further reaction with ace tic anhydride and hydrogen bromide in acetic acid afforded a mixture o f 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 d eblocked to ta-D-glycero-pent-2-enofuranosyl)-5-phenylcytosine (22). C atalytic hydrogenation of compound 20 over palladium and subsequent de blocking of the protected 2',3'-dideoxy derivative 23 gave 1-(2, xy-be ta-D-glycero-pentofuranosyl)-5-phenylcytosine (24).