Syntheses of 1-(5-deoxy-β-d-arabino-hexofuranosyl)cytosine

✍ Scribed by Masaharu Iwakawa; Olivier R. Martin; Walter A. Szarek

• Book ID: 102991012
• Publisher: Elsevier Science
• Year: 1983
• Tongue: English
• Weight: 568 KB
• Volume: 121
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(83)84009-9

✦ Synopsis

l-(5-Deoxy-P-D-arabinn-hexofutanoayl)cytosine (4'-homoara-C) (ll), a higher homolog of the antileukemic agent ara-C (1-B-D-arabinofuranosylcytosine), was prepared by two independent routes. The first one involved the inversion of configuration at C-2' of the D-rib0 epimer (1-(S-dzoxy-P-D-ribo-hexofuranosyl)cytosine, 4'-homocytidine) by the diphenylcarbonate technique; the 5deoxy-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-l,2-O-isopropylidene-3-O-p-tolylsulfonyl-ol-D-ribo-hex-5-enofuranose and reduction of the resulting iodide(s). In the second approach, Sdeoxy-l,Z-O-isopropylidene-3-O-p-tolylsulfonyl-~-D-xylo-hexofuranose was acetolyzed and condensed with 4-acetyl-N-his(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 'H-and '3C-n.m.r. spectra.