Tricyclic nucleosides derived from D-glucose. Synthesis and conformational behaviour

Abstract

Two anomeric nucleosides with tricyclic carbohydrate moieties, 3 and 14, are synthesised in 11 steps from diacetone-D-glucose, taking advantage of a stereoselective Grignard reaction, a stereoselective dihydroxylation and a regioselective tandem ring-closing procedure. The configuration of 3 is confirmed by measuring the ³J_HH coupling constants in connection with molecular modelling and ab initio calculations, as these exclude alternative tricyclic nucleoside structures. The conformational preference for 3 is described. The furanose ring is found to be in an O-4′-endo conformation and the γ torsion angle in the +ap range.