Diastereomerically pure nucleoside-5′-O-(2-thio-4,4-pentamethylene-1, 3,2-oxathiaphospholane)s-Substrates for synthesis of P-chiral derivatives of nucleoside-5′-O-phosphorothioates

Abstract

A method for stereocontrolled chemical synthesis of P-substituted nucleoside 5′-O-phosphorothioates has been elaborated. Selected 3′-O-acylated deoxyribonucleoside- and 2′,3′-O,O-diacylated ribonucleoside-5′-O-(2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane)s were chromatographically separated into P-diastereomers. Their reaction with anions of phosphorus-containing acids was highly stereoselective (≥90%) and furnished corresponding P-chiral α-thiodiphosphates and their phosphonate analogs with satisfactory yield. Copyright © 2010 Wiley-Liss, Inc.