title: Fluorinated Pyrimidine nucleosides. 1. Synthesis of a nitrogen analogue of the antitumor agent 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine hydrochloride.
abstract: The nitrogen-bridged compound 2,2'-anhydro-1-beta-D-arabinofuranosyl-2,4-diamino-5-fluoropyrimidinium chloride (2), an analogue of the antitumor agent anhydro-ara-FC (1), has been synthesized. 5-Fluorocytidine was converted into 1-beta-D-ribofuranosyl-2,4-diamino-5-fluoropyrimidinium chloride (4), but cyclization of 4 was not achieved due to a competing side reaction. The nitrogen bridge was therefore introduced by cyclization of 5-fluoroisocytidine (10) to give the 2,2'-imino-bridged compound 16. The latter was converted into 2 by the standard procedure of thiation, S-methylation, and treatment with ammonia. Compound 2, as well as a number of the synthetic intermediates, was tested for activity against S180 sarcoma in mice. None of the new compounds exhibited any antitumor activity.
mesh_terms: D003504:Ancitabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D003561:Cytarabine / Q000031:analogs & derivatives*; D008722:Methods; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D012513:Sarcoma, Experimental / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D003504:Ancitabine