Reduction of Thionucleosides: A Prebiotic Pathway to Deoxyribonucleosides

Abstract

The biosynthesis of 2′-deoxyribonucleosides is known to take place via the reduction of ribonucleotides, and the Principle of Continuity suggests to search for a similar pathway operating under prebiotic conditions. The facility by which the C-S bond can be reduced in comparison to the C-0 would favor 2′-thio-2′-deoxyribonucleosides as the most likely precursors. Previous work from our laboratory has presented a good case for the prebiotic existence of 2′-thio-2′-deoxycytidine which is not less plausible than the present argument for ribocytidine. The thio-analog is obtained from anhydro-araC with several sulfur-containing nucleophiles. The problem of reducing a C-S bond to C-H under prebiotic conditions has not yet received any attention. Besides the traditional Raney nickel treatment, we have now explored such plausible reductions as a) inorganic reduction by Fe(II), b) organic reduction by HCN, and c) photochemical reduction by UV light. All three methods proved to be suitable in producing deoxycytidine in 1 to 8% yield. This may be the best supported model of prebiotic synthesis of a deoxyribonucleoside.