Route efficiency assessment and review of the synthesis of β-nucleosides via N-glycosylation of nucleobases

Felix Kaspar,Anke Kurreck,Peter Neubauer,M. Rhia L. Stone

doi:10.1039/d0gc02665d

Abstract

Instead of focusing on maximizing glycosylation yield, future syntheses of nucleosides via N-glycosylation should aim to use shorter routes, fewer protecting groups and less chromatography to achieve more efficient and sustainable processes, as this E-factor analysis reveals.

Highlights

Nucleosides are highly functionalized biomolecules essential to life on earth and were among the first organic molecules on our planet.[1]
To enable more efficient and sustainable nucleoside synthesis via N-glycosylation, future efforts should focus on using non-chromatographic purification steps, running shorter routes and higher substrate loading to minimize waste accumulation
Since nucleosides will undoubtedly continue to be central to all areas of life science, we aimed to provide a transparent evaluation and investigated which routes to nucleosides would yield the most efficient and sustainable synthesis

Summary

Introduction

Nucleosides are highly functionalized biomolecules essential to life on earth and were among the first organic molecules on our planet.[1]. The desired linkage of a nucleobase to the anomeric center of a ribosyl moiety to yield a β-nucleoside often competes with several side reactions, including unselective nucleophilic attack (forming the α-nucleoside) and attack of other nucleophilic functional groups, affording complex mixtures of products. To address these obstacles, a variety of creative approaches have been developed to prepare β-nucleosides in high yield and selectivity. A variety of creative approaches have been developed to prepare β-nucleosides in high yield and selectivity These methods vary drastically regarding their strategy, number of steps, yield, reagents, and conditions employed, making it difficult to compare and evaluate different approaches

Objectives

Findings

Conclusion