Selective Deuteration Labelling of 2′-Deoxyguanosine at the Carbon C-4’ Position

Abstract

Abstract Selective incorporation of deuterium within the sugar moiety of nucleosides and oligonucleotides can be used for different purposes including isotopic effect determination in mechanistic studies, massspectrometry fragmentation investigations, nuclear magnetic resonance analyses. We wish to report a simple method which allows the selective deuteration labelling of 2'-deoxyguanosine at the C-4'position through the intermediary of 9-(2-deoxy-B-D-erythropento-1,5-dialdo-114-furanosyllquanine. Heating of aqueous pyridine solution [1:11 of 2′-deoxyguanosine-5′-aldehyde for 1 hr at 60°C leads to a partial epimerisation of carbon C-4' with subsequent formation of 9-(2-deoxy-α-L-threopento-1,5-dialdo-1,4-furanosyl)guanine in 40% yield. A likely intermediate of this reaction appears to be a 5'-enol derivative. Similar treatment of 2′-deoxyguanosine-5′-aldehyde in D20-pyridine [1-1] gives after NaBH4 reduction 60% of 2′-deoxyguanosine which is selectively deuterated at the C-4′ position. The extend of the i...