Application of experimental design methodology to the study of the synthesis of nucleosides

Abstract

A factorial design has been used to study the effect of three factors on the reaction between 4-amino-8Y-pyrazino[2,3-~]-1,2,6-thiadiazine 2,2-dioxide and 1,2,3,5-tetra-Q-acetyyl-p-D-ribofuranose. Reaction conditions have been found in which the usually less abundant N-8 isomer is selectively obtained. INTRODUCTIONIn a previous paper' we had described glycosylation of pyrazino[2,3-~]-1,2,6-thiadiazine derivatives in which the N-1 nucleosides were the major products (Scheme 1). Because, for biological reasons, we wanted to prepare larger amounts of the N-8 nucleoside we decided to methodologically study the operating conditions.