The synthesis, conformation and hydrolytic stability of an N,S-bridging thiophosphoramidate analogue of thymidylyl-3 ',5 '-thymidine
: Louis P. Conway, Satu Mikkola, AnnMarie C. O'Donoghoue, David R.W. Hodgson
Publisher: Royal Society of Chemistry
: Cambridge
: 2016
: Organic and Biomolecular Chemistry
: OBC
: 14
: 30
: 7361
: 7367
: 7
: 1477-0520
: 1477-0539
DOI: https://doi.org/10.1039/c6ob01270a
: http://pubs.rsc.org/en/content/articlelanding/2016/ob/c6ob01270a#!divAbstract
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+]
