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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.

SUBMITTER: McCabe Dunn JM

PROVIDER: S-EPMC5426439 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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The protecting-group free selective 3'-functionalization of nucleosides.

McCabe Dunn Jamie M JM Reibarkh Mikhail M Sherer Edward C EC Orr Robert K RK Ruck Rebecca T RT Simmons Bryon B Bellomo Ana A

Chemical science 20170118 4

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 ran ...[more]

PMID: 28553517

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