Selective Recognition of Alkyl Pyranosides in Protic and Aprotic Solvents

The design and synthesis of receptors capable of selective, noncovalent recognition of carbohydrates continues to be a signature challenge in bioorganic chemistry. We report a new generation of tripodal receptors incorporating three pyridine (compound <b>2</b>) or quinoline (compound <b>3</b>) rings around a central cyclohexane core for use in molecular recognition of monosaccharides in apolar and polar protic solvents. These tripodal receptors were investigated using ¹H NMR, UV, and fluorescence titrations in order to determine their binding abilities toward a set of octyl glycosides. Receptor <b>2</b> displayed the highest binding affinity reported to date for noncovalent 1:1 binding of an α-glucopyranoside in chloroform (<i>K</i>_a = 212 000 ± 27 000 M⁻¹) and an approximately 8-fold selectivity for the α anomer over the β anomer of the glucopyranoside. Most importantly, <b>2</b> retained its micromolar range of affinities toward monosaccharides in a polar and highly competitive solvent (methanol). The quinoline variant <b>3</b> also displayed micromolar binding affinities for selected monosaccharides in methanol (as measured by fluorescence) that were generally smaller than those of <b>2</b>. Compound <b>3</b> was found to follow a selectivity pattern similar to that of <b>2</b>, displaying higher affinities for glucopyranosides than for other monosaccharides. The binding stoichiometry was estimated to be 1:1 for the complexes formed by both <b>2</b> and <b>3</b> with glucopyranosides, as determined by Job plots. Nuclear Overhauser effect spectroscopy allowed for the derivation of a binding model consistent with the observed selectivities.