Syntheses of 1-(5-deoxy-beta-D-arabino-hexofuranosyl)cytosine

Abstract

1-(5-Deoxy-beta-D-arabino-hexofuranosyl)cytosine (4'-homoara-C) (11), a higher homolog of the antileukemic agent ara-C (1-beta-D-arabinofuranosylcytosine), was prepared by two independent routes. The first one involved the inversion of configuration at C-2' of the D-ribo epimer (1-(5-deoxy-beta-D-ribo-hexofuranosyl)cytosine, 4'-homocytidine) by the diphenylcarbonate technique; the 5-deoxy-D-ribo-hexofuranosyl moiety of 4'-homocytidine was obtained by way of an anti-Markovnikov addition of iodine trifluoroacetate to the double bond of 5,6-dideoxy-1, 2-O-isopropylidene-3-O-p-tolylsulfonyl-alpha-D-ribo-hex-5-enofu ranose and reduction of the resulting iodide(s). In the second approach, 5-deoxy-1,2-O-isopropylidene-3-O-p-tolylsulfonyl-beta-D-xylo-he xofuranose was acetolyzed and condensed with 4-acetyl-N-bis(trimethylsilyl)cytosine, and alkaline treatment gave 11 by way of a 2',3'-anhydro intermediate. The structure of 11, in particular the configuration at C-2', was confirmed by its 1H- and 13C-n.m.r. spectra.