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

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 k obs pro fi le displays a pH-independent
region between approximately pH 7 and 10 ( t 1/2 ∼ 13 days). Under acidic conditions, k obs displays a fi rst
order dependence on [H ₃ O⁺]