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RESEARCH ARTICLE
Contents Vol 73(10)

Operationally Simple Regioselective 5′-Phosphorylation of Unprotected 5-Ethynyl-2′-deoxyuridine Analogues

David H. Hilko A B , Laurent F. Bornaghi A and Sally-Ann Poulsen https://orcid.org/0000-0003-4494-3687 A B
+ Author Affiliations
- Author Affiliations

A Griffith Institute for Drug Discovery (GRIDD), Griffith University, Brisbane, Nathan, Qld 4111, Australia.

B Corresponding authors. Email: d.hilko@griffith.edu.au; s.poulsen@griffith.edu.au

Australian Journal of Chemistry 73(10) 1010-1019 https://doi.org/10.1071/CH19529
Submitted: 17 October 2019  Accepted: 28 January 2020   Published: 15 May 2020

Abstract

Here, we present the development of a straightforward methodology to regioselectively phosphorylate the 5′-OH group of unprotected nucleosides. We employ cyclosaligenyl phosphoramidite reagents together with pyridinium trifluoroacetate as activator, followed by in situ oxidation to prepare a panel of novel nucleoside-based chemical probes, ProLabel compounds 4–15. Alternative procedures for this transformation are available, but are limited in number and scope. Furthermore, the benefits of the new methodology include milder reaction conditions, wider solvent applicability, and, by avoiding sensitive reagents, a more straightforward handling of reagents, reactions, and workup processes. The panel of novel cyclosaligenyl phosphotriester uridine ProLabels have variable 2′ substituents (H, F, Cl, Br, I) as well as four different cyclosaligenyl groups that would span a range of half-lives for in vitro applications.


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