Fluorinated pyrimidine nucleosides. 1. Synthesis of a nitrogen analog of the antitumor agent 2,2'-anhydro-1-.beta.-D-arabinofuranosyl-5-fluorocytosine hydrochloride

• Published in: Journal of medicinal chemistry Vol. 20; no. 3; pp. 344 - 348
• Main Author: Cook, Alan F
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.03.1977
• Subjects: Ancitabine - analogs & derivatives; Ancitabine - chemical synthesis; Ancitabine - therapeutic use; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - therapeutic use; Cytarabine - analogs & derivatives; Methods; Mice; Models, Molecular; Molecular Conformation; Sarcoma, Experimental - drug therapy
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00213a006

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.