The synthesis, conformation and hydrolytic stability of an N,S-bridging thiophosphoramidate analogue of thymidylyl-3′,5′-thymidine?

Organic & Biomolecular Chemistry Pub Date: 2016-07-11 DOI: 10.1039/C6OB01270A

Abstract

A 3′-N,5′-S-bridging thiophosphoramidate analogue of thymidylyl-3′,5′-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 (t1/2 ～13 days). Under acidic conditions, kobs displays a first order dependence on [H3O+].

Graphical abstract: The synthesis, conformation and hydrolytic stability of an N,S-bridging thiophosphoramidate analogue of thymidylyl-3′,5′-thymidine
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