(Digital Presentation) Scalable Synthesis of Versatile Intermediate for Azanucleoside Derivatives Via directanodic N-α Hydroxylation

Abstract

Azanucleosides are found to show unique pharmacological activities even without incorporating into oligonucleotides and are used as anticancer and antivirus agents. Practical synthesis routes of azanucleosides are of exceptional importance to enhance the development of (oligo)nucleotide therapeutics. Previously, we reported the synthetic methods of azanucleosides by using electrochemical approaches, which has now been offering green and sustainable redox options in the field of synthetic organic chemistry. However, scaling-up of the reactions remains challenging since continuous production is essentially not possible. Herein, we report the direct anodic N-α hydroxylation of prolinol derivatives as useful intermediates for azanucleosides. Cyclic voltammetry study clearly reveals that the presence of water facilitates the oxidative electron transfer events. The reaction is applicable for large scale production and thus could enhance the development of (oligo)azanucleotide therapeutics.