Artificial carbohydrate receptors using noncovalent interactions for sugar binding provide valuable model systems to study the underlying principles of carbohydrate-based molecular recognition processes. In addition, well-designed artificial receptors may serve as a basis for the development of saccharide sensors or therapeutics that intervene in biologically important carbohydrate recognitions. Several different strategies have been employed for the design of such synthetic systems. The main focus of this tutorial review is on the carbohydrate binding capabilities of receptors possessing an acyclic structure and employing noncovalent interactions for sugar binding. The acyclic scaffold provides simplicity in the synthetic plan for many modifications of the receptor structure, supplying a base for systematic studies toward recognition motifs for carbohydrates. The review covers both some earlier examples and newer developments in this field.

The binding motifs found in the crystal structures of protein-carbohydrate complexes have been successfully mimicked with simple acyclic pyridine- and pyrimidine-based receptors. A full discussion of the recognition motifs observed in the crystal structures of complexes of receptors 1 and 3 with glucopyranosides 4a and 4b is provided. A remarkable similarity of these motifs to those observed in the crystal structures of sugar-binding proteins and those found by molecular modeling is shown. In addition, the recognition properties of the new pyrimidine receptor 3 toward monosaccharides 4-6 are described. This molecule has been established as a highly effective receptor for beta-glucopyranosides.

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The synthesis and binding properties for carbohydrates of several artificial, acyclic receptors containing two or three heterocyclic recognition units covalently attached to a phenyl spacer is described. These host molecules having uncharged hydrogen-bonding sites were used in a systematic study towards the evaluation of recognition motifs for carbohydrates. A novel effective, acyclic hydrogen-bonding receptor possessing naphthyridine-amide moieties as heterocyclic recognition units has been developed.

The binding motifs found in the crystal structures of complexes formed between artificial receptors and monosaccharides, reported previously by our group, have inspired us to design new macrocyclic and acyclic receptors, which were expected to form strong 1:1 complexes with monosaccharides, in particular with β-glucosides, through participation in the formation of CH-π interactions and hydrogen bonds with the sugar substrate. As first representatives of these compounds we have prepared the macrocycles 8-12 and the acyclic molecules 13-16, incorporating two central triethylbenzene units. The new compounds had been designed to bind monosaccharides via interactions of both central benzene rings with the sugar CH groups. Initial binding studies have confirmed the expected favorable binding capabilities of the macrocyclic compounds and indicated interesting binding properties of the acyclic analogues.