Synthesis of 5′-carboxymethylsulfonyl-5′-deoxyribonucleosides under mild hydrolytic conditions: a new class of acidic nucleosides as inhibitors of ribonuclease A

Abstract

5'-Carboxymethylsulfonyl-5'-deoxy-uridine, -cytidine and -adenosine were selected as a new class of potential RNase A inhibitors. The key step of the synthesis from the corresponding esters is crucially dependent on the nature of the base and only trimethyltin hydroxide afforded the desired products under extremely mild basic hydrolytic conditions. The cytidine analogue was found to be the best competitive inhibitor of RNase A in this series (K_i = 22 ± 2 μM).