Chiral Carbocyclic Nucleosides from d-Glucose: Enantiodivergent Synthesis and One-Pot Entry of Dimethylamino Functionality in the Purine Rings

Abstract

Cyclization of appropriately designed enose−nitrones derived from d-glucose, having nitrone at C-5 or C-1 and allylic/homoallylic functionalities at C-3 of the sugar backbone, afforded polyhydroxylated aminocarbocycles which were subsequently used as the precursors for carbocyclic nucleoside analogues (11, 13, 16, 21, and 23). The enantiodirecting synthesis of both the enantiomeric pairs of nucleoside analogues 11 and 13, 21a and 23a, and 21c and 23c, has also been demonstrated by judiciously applying intramolecular nitrone cycloaddition (INC) reaction. An interesting observation was that in the cyclization reaction of pyrimidine ring to purine ring in DMF solvent, the substitution of C-6 chloro group with a dimethylamino functionality also occurred spontaneously under mild condition, though similar reactions are reported to occur at higher temperature. The hydrogen bonding between N-3 of the purine ring and an appropriate hydroxy substituent in the carbocycle seems to play a crucial role in this reaction.