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
A B
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.
References
[1] L. P. Jordheim, D. Durantel, F. Zoulim, C. Dumontet, Nat. Rev. Drug Discov. 2013, 12, 447.| Crossref | GoogleScholarGoogle Scholar | 23722347PubMed |
[2] A. S. Ray, K. Y. Hostetler, Antiviral Res. 2011, 92, 277.
| Crossref | GoogleScholarGoogle Scholar | 21878354PubMed |
[3] S. B. Buck, J. Bradford, K. R. Gee, B. J. Agnew, S. T. Clarke, A. Salic, Biotechniques 2008, 44, 927.
| Crossref | GoogleScholarGoogle Scholar | 18533904PubMed |
[4] H. G. Gratzner, Science 1982, 218, 474.
| Crossref | GoogleScholarGoogle Scholar | 7123245PubMed |
[5] M. Tera, S. M. K. Glasauer, N. W. Luedtke, ChemBioChem 2018, 19, 1939.
| Crossref | GoogleScholarGoogle Scholar | 29953711PubMed |
[6] N. Huynh, C. Dickson, D. Zencak, D. H. Hilko, A. Mackay-Sim, S. A. Poulsen, Chem. Biol. Drug Des. 2015, 86, 400.
| Crossref | GoogleScholarGoogle Scholar | 25557046PubMed |
[7] S. Seo, K. Onizuka, C. Nishioka, E. Takahashi, S. Tsuneda, H. Abe, Y. Ito, Org. Biomol. Chem. 2015, 13, 4589.
| Crossref | GoogleScholarGoogle Scholar | 25777799PubMed |
[8] C. J. Lovitt, D. H. Hilko, V. M. Avery, S.-A. Poulsen, Bioorg. Med. Chem. 2016, 24, 4272.
| Crossref | GoogleScholarGoogle Scholar | 27460697PubMed |
[9] U. Pradere, E. C. Garnier-Amblard, S. J. Coats, F. Amblard, R. F. Schinazi, Chem. Rev. 2014, 114, 9154.
| Crossref | GoogleScholarGoogle Scholar | 25144792PubMed |
[10] M. Lorey, C. Meiera, E. De Clercq, J. Balzarini, Nucleosides Nucleotides 1997, 16, 789.
| Crossref | GoogleScholarGoogle Scholar |
[11] S. C. Tobias, R. F. Borch, J. Med. Chem. 2001, 44, 4475.
| Crossref | GoogleScholarGoogle Scholar | 11728193PubMed |
[12] M. Lorey, C. Meier, E. De Clercq, J. Balzarini, Nucleosides Nucleotides 1997, 16, 1307.
| Crossref | GoogleScholarGoogle Scholar |
[13] Y. Kato, N. Oka, T. Wada, Tetrahedron Lett. 2006, 47, 2501.
| Crossref | GoogleScholarGoogle Scholar |
[14] S. M. Graham, S. C. Pope, Org. Lett. 1999, 1, 733.
| Crossref | GoogleScholarGoogle Scholar | 10823200PubMed |
[15] I. Zlatev, Y. Kato, A. Meyer, J.-J. Vasseur, F. Morvan, Tetrahedron Lett. 2006, 47, 8379.
| Crossref | GoogleScholarGoogle Scholar |
[16] F. Mugnier, C. Meier, Nucleosides Nucleotides Nucleic Acids 1999, 18, 941.
| Crossref | GoogleScholarGoogle Scholar |
[17] S. L. Beaucage, M. H. Caruthers, Tetrahedron Lett. 1981, 22, 1859.
| Crossref | GoogleScholarGoogle Scholar |
[18] C. Ducho, U. Görbig, S. Jessel, N. Gisch, J. Balzarini, C. Meier, J. Med. Chem. 2007, 50, 1335.
| Crossref | GoogleScholarGoogle Scholar | 17328534PubMed |
[19] I. Sarac, C. Meier, Chem. – Eur. J. 2015, 21, 16421.
| Crossref | GoogleScholarGoogle Scholar | 26517040PubMed |
[20] D. H. Hilko, L. F. Bornaghi, S.-A. Poulsen, J. Org. Chem. 2018, 83, 11944.
| Crossref | GoogleScholarGoogle Scholar | 30153729PubMed |
[21] A. B. Neef, N. W. Luedtke, Proc. Natl. Acad. Sci. USA 2011, 108, 20404.
| Crossref | GoogleScholarGoogle Scholar | 22143759PubMed |
[22] C. Meier, Angew. Chem. Int. Ed. Engl. 1996, 35, 70.
| Crossref | GoogleScholarGoogle Scholar |
