Issue 4, 2017

The protecting-group free selective 3′-functionalization of nucleosides

Abstract

The direct and chemoselective 3′-phosphoramidation, phosphorylation and acylation of nucleosides are described. Upon the discovery of a novel 3′-phosphorylamidation of therapeutic nucleoside analogues with DBU, we explored the mechanism of this rare selectivity through a combination of NMR spectroscopy and computational studies. The NMR and computational findings allowed us to develop a predictive computational model that accurately assesses the potential for 3′-functionalization for a broad range of nucleosides and nucleoside mimetics. The synthetic utility of this model was exemplified by demonstration on a broad scope of nucleosides and electrophiles yielding targets that were previously only accessible via a protection/deprotection sequence or an enzymatic approach.

Graphical abstract: The protecting-group free selective 3′-functionalization of nucleosides

Supplementary files

Article information

Article type
Edge Article
Submitted
18 Nov 2016
Accepted
06 Jan 2017
First published
18 Jan 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 2804-2810

The protecting-group free selective 3′-functionalization of nucleosides

J. M. McCabe Dunn, M. Reibarkh, E. C. Sherer, R. K. Orr, R. T. Ruck, B. Simmons and A. Bellomo, Chem. Sci., 2017, 8, 2804 DOI: 10.1039/C6SC05081F

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