Stereoselective synthesis of novel 4′-methylsulfanyl-pyrimidine ribonucleosides by means of nucleophilic substitution of the 4′-benzoyloxy leaving group

Abstract

A synthetic route for the novel nucleosides 4′-methylsulfanyluridine (20a) and –cytidine (26) has been developed. This route consists of two steps; 1) preparation of 4′-O-benzoyloxy-xylofuranosylnucleoside 13 through electrophilic iodo-benzoyloxylation to 4′,5′-unsaturated uracil nulesoside 9 and replacement of the iodo-substituent at the 5′-position with the benzoyloxy group, 2) nucleophilic substitution of 13 with Me₃SiSMe leading to the 4′-α-methylsulfanylnucleoside 14a stereoselectively. The possible reaction mechanism of the 5′-deoxy-5′-iodonucleosides 10a and 10b with AgOBz is discussed. The transformation of the xylofuranosyl moiety of 14a into the ribonucleoside 20a was performed on the basis of the ring-opening of the O²,2′-anhydronucleoside 24 with benzoate ion. In this study, 4′-methylsulfanylcytidine 26 was also synthesized.