Synthesis of isotopically labeled d-[1′-13C]ribonucleoside phosphoramidites

The preparation of fully protected labeled diisopropylamino-β-cyanoethyl-[1′-13C]ribonucleoside phosphoramidites with regioisomeric purity is described. We demonstrated in this paper that a regioselective 2′-O-silylation, through a 3′,5′-O-di-tert-butylsilanediyl protection, has been applied for the synthesis of [1′-13C]ribonucleoside phosphoramidite units. This method allowed us to obtain only the desired 2′-O-silyl-3′-O-phosphoramidites avoiding the undesired 3′-O-silyl-2′-O-phosphoramidite nucleosides isolated by standard procedures. This is a suitable procedure to RNA precursors with respect to the isotope-containing precursors.