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

Abstract

The N bridged compound 2,2''-anhydro-1-.beta.-D-arabinofuranosyl-2,4-diamino-5-fluoropyrimidinium chloride was 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 N bridge was therefore introduced by cyclization of 5-fluoroisocytidine to give the 2,2''-imino-bridged compound. The latter was converted into 2 by the standard procedure of thiation, S-methylation and treatment with ammonia. Compound 2 and a number of the synthetic intermediates were tested for activity against S180 sarcoma in mice. None of the new compounds exhibited any antitumor activity.