Nucleosides. 116. 1-(.beta.-D-Xylofuranosyl)-5-fluorocytosines with a leaving group on the 3' position. Potential double-barreled masked precursors of anticancer nucleosides

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Abstract
Syntheses of 5 pairs of cytosine and 5-fluorocytosine xylofuranosyl nucleosides in which the 3''-hydroxyl group is replaced by Cl, Br, I, OMs or OTs are described. Those xylosyl nucleosides with a good leaving group at the 3'' position exhibit good inhibitory activity against L5178Y and P815 mouse leukemic cells in vitro at rather low concentrations and like that of ara-C this cytotoxicity is reversed by 2''-deoxycytidine but not by thymidine. Xylosylcytosines are not active against ara-C resistant lines of L5178Y and P815 cells, the corresponding 5-fluorocytosine analogs exhibit significant cytotoxicity against these ara-C resistant leukemic cell lines and this activity is reversed by thymidine but not by deoxycytidine. These data support the double-barreled masked precursor hypothesis in that xylosyl-5-fluorocytosines substituted at the 3''-position by a good leaving group exhibit activity akin to that of ara-C in the ara-C sensitive lines, while these nucleotides act as 5-fluoropyrimidines in the ara-C resistant lines.