Regioselective synthesis of 1,3,5-13C3 and 2,4-13C2-labeled 2-deoxyribonolactones

The synthesis of 1,3,5-C-13(3)- and 2,4-C-13(2)-labeled 5-O-bromobenzyl-2-deoxyribonolactones 2, precursors to C-13-enriched nucleoside phosphoramidites for solid-phase synthesis of DNA oligonucletides, is described. An equimolar combination of these two multiply labeled lactones affords a "population-labeled" mixture of isotopomers which exhibits an approximately 50-fold increase in the sensitivity of C-13-NMR compared to natural abundance measurements. The C-13-C-13 2-bond and 4-bond coupling constants are reported for the lactones; all are < 2Hz, confirming that this labeling scheme should be especially useful for NMR-relaxation measurements.