The chemical synthesis of the R_p and S_pdiastereomers of uridyl (3′-5′) adenyl O, O-phosphorothioate

A procedure is described for the synthesis of the title compounds via phosphotriester intermediates. The 2-cyanoethyl group is used to protect the P-SH function during the course of the synthesis. Resolution of the phosphorus-diastereomers is accomplished at the phosphotriester stage. Removal of the 2-cyanoethyl group without racemization at phosphorus, followed by removal of the other protective groups affords the optically pure diastereomers of uridyl (3′ - 5′) adenyl 0,0-phospho- rothioate. Their designation as R and S follows from the stereospecificity of the hydrolysis catalyzed by RNase A.