Collect. Czech. Chem. Commun. 1998, 63, 222-230

Synthesis of Some 6-Substituted 5-Azacytidines

Naeem B. Hanna, Milena Masojídková, Pavel Fiedler and Alois Pískala

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


Protected 6-substituted benzyl, phenyl and chloromethyl derivatives of 5-azacytidine 8-10 have been prepared by addition of phenylacetyl- (2), benzoyl- (3) or (chloroacetyl)guanidine (4) to 2,3,5-tri-O-benzoyl-β-D-ribosyl isocyanate (1) and subsequent silylation-mediated cyclization of the obtained acyl(carbamoyl)guanidines 5-7. 4-Amino-6-phenyl-1,3,5-triazin-2(1H)-one (12) was obtained by condensation of carbamoylguanidine (13) with methyl benzoate in presence of methanolic sodium methoxide or by condensation of 13 with triethyl orthobenzoate in N,N-dimethylformamide. Stannic chloride catalyzed condensation of silylated 6-phenyl derivative 11 with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribose (14) in 1,2-dichloroethane afforded a 1.2 : 1 mixture of N1 and N3 nucleosides 9 and 15, respectively. Methanolysis of the protected compounds 8-10 and 15 gave the respective free nucleosides 16-19. The latter compounds inhibited the growth of bacteria E. coli B to a much lower extent than the unsubstituted 5-azacytidine.

Keywords: 5-Azapyrimidines; 1,3,5-Triazines; Nucleosides; Circular dichroism; Antibacterial activity.