An improved synthesis of guanosine TNA phosphoramidite for oligonucleotide synthesis.

ABSTRACT

The chemical synthesis of guanosine nucleosides generates both the N9 and N7 regioisomers, which require careful separation to obtain the desired N9 isomer. To preferentially obtain the N9 isomer, a bulky diphenylcarbamoyl (DPC) group can be installed at the O6 position of guanine. However, installation of the DPC group presents a challenging task due to low solubility of the N-acetyl protected guanine. Here we report the usage of commercially available 2-amino-6-chloro purine as a new strategy that offers a more efficient route to the synthesis of the guanine phosphoramidite of threose nucleic acid (TNA).