Reexamination of Reverse Anomeric Effect (RAE)

Anomeric effect is the preference for an electronegative substituent at C1 of pyranose derivatives to adopt an axial position instead of the sterically favored equatorial orientation. The anomeric effect has been observed in a number of structural types and is of great importance for the conformational analysis of biologically important molecules such as carbohydrates and nucleosides. However in some cases positively charged substituents at C1 prefer an equatorial orientation. This phenomenon was first observed in glycosyl pyridinium ions and was credited to a so-called reverse anomeric effect (RAE), suggesting a stereoelectronic origin. Experimental evidence for this RAE is sparse and ambiguous, and it has never been studied in structurally similar C-glycoside molecules. Our research set out to synthesize and reexamine the RAE in C-glycoside molecules using a NMR titration method. The attempted synthesis of model compounds failed and an alternate method using mass spectrometry was examined. This study involved a relative proton affinity determination of alpha and beta glycosyl imidazoles under solvent free condition, using ESI FT-ICR mass spectrometry. This method is highly advantageous since it will reveal the intrinsic nature of the glycosides and will eliminate the solvent contribution to the RAE. Preliminary data obtained from proton transfer reactions indicates that the beta glucoacetyl imidazole has a higher proton affinity than the alpha glucoacetyl imodazole. Determination of rate constants and complete kinetic study is currently in progress