Efficient chemical synthesis of N²-modified guanosine derivatives: a versatile probes for mRNA labeling

An efficient method for the synthesis of N²-modified guanosine nucleotides such as N²-[benzyl-N-(propyl)carbamate]-guanosine-5'-O-monophosphate, N²-[benzyl-N-(propyl)carbamate]-guanosine-5'-O-diphosphate, N²-[benzyl-N-(propyl)carbamate]-guanosine-5'-O-triphosphate, and N²-[benzyl-N-(propyl)carbamate]-N⁷-methyl-guanosine-5'-O-diphosphate, starting from the corresponding nucleotide is described. The overall reaction involves the condensation between the exocyclic amine of guanosine nucleotide with 3-[(benzyloxycarbonyl)amino]propionaldehyde in aqueous methanol, followed by reduction using sodium cyanoborohydride to furnish the corresponding N²-modified guanosine nucleotide in moderate yield with high purity (>99.5%).