Stereochemical Course of Cerium(IV)-Catalyzed Hydrolysis of Cyclic Nucleotides

Abstract

CeIV 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 Sp cTMPS the ratio was 3:2. Both diastereoisomers of thymidine 3‘,5‘-cyclic [18O]thiophosphate have been synthesized, and the stereochemical course of the hydrolysis reaction catalyzed by CeIV 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.