The Synthesis, Conformation and Hydrolytic Stability of an N,S-bridging Thiophosphoramidate Analogue of Thymidylyl-3ʹ,5ʹ-Thymidine

Conway, L.P.; Mikkola, S.; O’Donoghue, A.C.; Hodgson, D.R.W.

Abstract

A 3'-N,5'-S-bridging thiophosphoramidate analogue of thymidylyl-3ʹ,5ʹ-thymidine was synthesised under aqueous conditions. 1H NMR conformational measurements show that the 3'-N-substituted deoxyribose ring is biased towards the 'north', RNA-like conformation. Rate constants for hydrolysis of the analogue were measured at 90 °C in the pH range 1.3-10.9. The pH-log kobs profile displays a pH-independent region between approximately pH 7 and 10 (t½ ~13 days). Under acidic conditions, kobs displays a first order dependence on [H3O+].

Citation

Conway, L., Mikkola, S., O’Donoghue, A., & Hodgson, D. (2016). The Synthesis, Conformation and Hydrolytic Stability of an N,S-bridging Thiophosphoramidate Analogue of Thymidylyl-3ʹ,5ʹ-Thymidine. Organic and Biomolecular Chemistry, 14(30), 7361-7367. https://doi.org/10.1039/c6ob01270a

• Journal Article Type: Article
• Acceptance Date: Jul 11, 2016
• Online Publication Date: Jul 11, 2016
• Publication Date: Aug 14, 2016
• Deposit Date: May 26, 2016
• Publicly Available Date: Jul 12, 2016
• Journal: Organic and Biomolecular Chemistry
• Print ISSN: 1477-0520
• Electronic ISSN: 1477-0539
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 30
• Pages: 7361-7367
• DOI: https://doi.org/10.1039/c6ob01270a
• Public URL: https://durham-repository.worktribe.com/output/1383476