Stereoselective synthesis of 4'-selenonucleosides using the Pummerer glycosylation reaction

Abstract

The syntheses of four selenonucleosides, namely 4'-beta-selenoadenosine, -cytidine, -thymidine, and -uridine are described. Commercially available D-ribonolactone was converted to the key intermediate 1,4-anhydro-4-seleno-D-ribitol in seven steps in overall excellent yield. Oxidation of the seleno-d-ribitol with MCPBA gave a single diastereomeric selenoxide in excellent yield, which upon Pummerer reaction in the presence of silylated purine or pyrimidine bases gave stereoselectively the corresponding 4'-beta-selenonucleosides. The stereochemistry at the anomeric center was determined by means of 1D-NOE experiments.