Synthesis of pyrimidine analogues of the nucleoside antibiotic ascamycin

Abstract

AbstractFour analogues of ascamycin 〈5′‐O‐[N‐(L‐alanyl)sulfamoyl]‐2‐chloroadenosine〉 (1) in which the 2‐chloroadenosine moiety has been replaced by uridine, thymidine, cytidine, and 2′‐deoxy‐5‐methylcytidine have been synthesized by selective aminoacylation of the 5′‐O‐sulfamoyl derivatives 2, 9, 14, and 21 of 2′,3′‐di‐O‐acetyluridine, 3′‐O‐acetylthymidine, 2′,3′‐O‐isopropylidenecytidine, and 3′‐O‐acetyl‐2′‐deoxy‐5‐methylcytidine, respectively, with Boc‐L‐Ala‐OSu in DMF and in the presence of DBU, followed by removal of the protecting groups. Similarly, 5′‐O‐[N‐(D‐alanyl)sulfamoyl]uridine (8) has been prepared from Boc‐D‐Ala‐OSu and 2. Compounds 14 and 21 were directly prepared by sulfamoylation of the 4‐N‐(dimethylamino)methylene derivatives 13 and 20 of 2′,3′‐O‐isopropylidenecytidine and 3′‐O‐acetyl‐2′‐deoxy‐5‐methylcytidine, respectively, via the intermediate 5′‐O‐tributyltin derivatives. Compound 20 was obtained from 5′‐O‐(tert‐butyldimethylsilyl)thymidine (17) by a route involving acetylation, conversion of the thymidine moiety into 5‐methylcytosine through the corresponding triazolylpyrimidinone, and amidine protection.