Improved antitumor effects in 3'-branched homologs of 2'-deoxythioguanine. Synthesis and evaluation of thioguanine nucleosides of 2,3-dideoxy-3-(hydroxymethyl)-D-erythro-pentofuranose

Publisher Website
Google Scholar
Abstract
The 3-(hydroxymethyl) branched homolog of 2-deoxyribofuranose was synthesized from the corresponding branched ribofuranose 2-O-(S-methyl dithiocarbonate) with tributyltin hydride in the 1st direct, 1-step deoxygenation at C-2 of a ribofuranose. Nucleoside coupling afforded the corresponding 3''-branched 2''-deoxyribonucleosides of thioguanine. The .alpha.- and .beta.-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 analog .alpha.-2''-deoxythioguanosine. Apparently the hydroxy functions at the 3'' and 5'' positions of 2''-deoxynucleosides are interchangeable on the tumor enzymes, the furanose ring O2 and 2''-methylene are correspondingly interchangeable and acceptance by the enzymes is improved if primary hydroxyls are provided at both the 3'' and 5'' positions.

This publication has 0 references indexed in Scilit: