A New Family of Chiral Binaphthv1-Derived Cyclophane Receptors: Complexation of Pyranosides

摘要

Carbohydrate recognition is central to many biological processes, including the transmission of disease and the operation of the immune system. Carbohydrates are suitable molecules for recognition, because the) have a much greater capacity to store information than other biopolymers. The stud) of these recognition processes can be either carried out directly on biological systems, for example by analyzing the interactions in protein-carbohydrate complexes by X-ray crystallography or in enzyme-linkedimmunosorbent assays, or by synthesizing simpler analogous receptors whose binding properties can be systematically varied and analyzed. We targeted the chiral receptors la —d (Scheme 1). which show a remarkable degree of preorganization: six, eight, orten OH groups converge upon a central cavity providing a ring of H-bonding sites for carbohydrate recognition. These receptors, derived from the 3,3'-diethynyl-l.l'-binaphthyl-2,2'-diol spacer 2. allow economy in the synthesis of a wide range of hosts.The introduction of linking groups X between the acetylenes would widen the cavity and provide enough space either to replace the convergent OH groups with other H-bonding residues or to bind di- and higher oligosaccharides. These linking groups could also offer a foundation on which to attach a hydrophobic floor parallel to the plane of H-bonding sites; Lemieux has convincingly shown that hydrophobic desolvation and van der Waals interactions are at least as important for biological carbohydrate binding in aqueous solution as the H-bonding interactions. Varying the divergent R groups at the periphery should lead to receptors soluble in solvents of any desired polarity, including water. Here we report the synthesis of the neutral receptors (R,R,R)-( -)-3 and (R.R.R.RH — )-4, and of the tetraanion-ic receptor (R,R,R,R)-( — )-5, as well as preliminary binding studies with pyranosides.