Skip to main content

Research Repository

Advanced Search

Synthesis of fluorinated carbocyclic pyrimidine nucleoside analogues

Benckendorff, Caecilie; Slyusarchuk, Valentyna D.; Huang, Ningwu; Lima, Marcelo A.; Smith, Mark; Miller, Gavin J.

Synthesis of fluorinated carbocyclic pyrimidine nucleoside analogues Thumbnail


Valentyna D. Slyusarchuk

Ningwu Huang

Mark Smith


Analogues of the canonical nucleosides have a longstanding presence and proven capability within medicinal chemistry and drug discovery research. The synthesis reported herein successfully replaces furanose oxygen with CF2 and CHF in pyrimidine nucleosides, granting access to an alternative pharmacophore space. Key diastereoselective conjugate addition and fluorination methodologies are developed from chiral pool materials, establishing a robust gram-scale synthesis of 6'-(R)-monofluoro- and 6'-gem-difluorouridines. Vital intermediate stereochemistries are confirmed using X-ray crystallography and NMR analysis, providing an indicative conformational preference for these fluorinated carbanucleosides. Utilising these 6'-fluorocarbauridine scaffolds enables synthesis of related cytidine, ProTide and 2'-deoxy analogues alongside a preliminary exploration of their biological capabilities in cancer cell viability assays. This synthetic blueprint offers potential to explore fluorocarbanucleoside scaffolds, indicatively towards triphosphate analogues and as building blocks for oligonucleotide synthesis.


Benckendorff, C., Slyusarchuk, V. D., Huang, N., Lima, M. A., Smith, M., & Miller, G. J. (2022). Synthesis of fluorinated carbocyclic pyrimidine nucleoside analogues. Organic and Biomolecular Chemistry, 20(47), 9469 - 9489.

Journal Article Type Article
Acceptance Date Nov 13, 2022
Online Publication Date Nov 14, 2022
Publication Date Dec 7, 2022
Publicly Available Date May 30, 2023
Journal Organic & Biomolecular Chemistry
Print ISSN 1477-0520
Electronic ISSN 1477-0539
Publisher Royal Society of Chemistry
Volume 20
Issue 47
Pages 9469 - 9489
Keywords Nucleosides, Chemistry, Pharmaceutical, Pyrimidine Nucleosides
Publisher URL
Additional Information Open Access Article. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.


You might also like

Downloadable Citations