IMPROVED ANTI-TUMOR EFFECTS IN 3'-BRANCHED HOMOLOGS OF 2'-DEOXYTHIOGUANOSINE - SYNTHESIS AND EVALUATION OF THIOGUANINE NUCLEOSIDES OF 2,3-DIDEOXY-3-(HYDROXYMETHYL)-D-ERYTHRO-PENTOFURANOSE

The 3-(hydroxymethyl) branched homologue of 2-deoxyribofuranose was synthesized from the corresponding branched ribofuranose 2-0-(S-methyl dithiocarbonate) with tributyltin hydride in the first direct, one-step deoxygenation at C-2 of a ribofuranose. Nucleoside coupling afforded the corresponding 3'-branched 2'-deoxyribonucleosides of thioguanine. The α- and β-nucleosides were equally inhibitory to growth of WI-L2 human lymphoblastoid cells, were phosphorylated and incorporated into the DNA of Mecca lymphosarcoma in mice to the same degree, and were more effective in these tests than the parent analogue α-2'-deoxythioguanosine. These results indicate that the hydroxy functions at the 3' and 5' positions of 2-deoxynucleosides are interchangeable on the tumor enzymes, that the furanose ring oxygen and 2'-methylene are correspondingly interchangeable, and that acceptance bv the enzymes is improved if primary hydroxyls are provided at both the 3' and 5' positions. © 1979, American Chemical Society. All rights reserved.