Stereochemical course of cerium(IV)-catalyzed hydrolysis of cyclic nucleotides

Ce-IV has been shown to catalyze the hydrolysis of thymidine 3',5'-cyclic thiophosphate (cTMPS) to give a mixture of 3'-TMPS and 5'-TMPS with rates comparable to those previously reported for cAMP and cTMP. The ratio of the 3'-TMPS and 5'-TMPS products was dependent on the absolute configuration of the cTMPS; starting from Rp cTMPS, with the sulfur equatorial, the 3'-TMPS:5'-TMPS ratio was ca. 7:1 whereas for the corresponding S-p cTMPS the ratio was 3:2. Both diastereoisomers of thymidine 3',5'-cyclic [O-18]-thiophosphate have been synthesized, and the stereochemical course of the hydrolysis reaction catalyzed by Ce-IV has been determined. In each case, the reaction proceeds with clean inversion of configuration, consistent; with coordination of the metal ion to the exocyclic oxygen substituent and delivery of the hydroxide nucleophile from one of the remaining metal coordination sites with in-line geometry.