4′-Aza-3′,5′-dihomothymidine and Derivatives

Abstract

A series of 3′-branched 4′-azanucleoside analogues have been prepared. These compounds comprise three asymmetric atoms, two carbons and one nitrogen. They constitute nucleoside analogues imparted with a “flickering configuration”, the nitrogen inversion replacing a D-L epimerization of their natural congeners. The 1′,3′-cis and 1′,3′-trans isomers have been separated and their configuration established by ¹H NMR and the X-ray diffraction structure of one crystalline example. The configurations of the frozen invertomers were assessed by low temperature ¹H NMR experiments assisted by molecular mechanics simulations. None of these compounds exhibited any significant in vitro antiviral activity.