Cycloalkyl Groups as Subunits of Artificial Carbohydrate Receptors: Effect of Ring Size of the Cycloalkyl Unit on the Receptor Efficiency

Abstract

1,3,5‐Trisubstituted 2,4,6‐triethylbenzenes consisting of isopropyl groups as recognition units have previously been shown to have interesting binding properties towards selected carbohydrates. The design of such artificial carbohydrate receptors was inspired by the mode of action of carbohydrate‐binding proteins, namely by the participation of the isopropyl side chain of valine in the formation of van der Waals interactions with the carbohydrate substrate. This study aimed to investigate how the replacement of the isopropyl groups by other structural motifs, such as cycloalkyl groups of varying sizes (three to seven‐membered rings), influences the binding properties of the acyclic compounds towards carbohydrates. The cyclopropyl moiety represents a cyclic analog of the isopropyl group, whereas the other cycloalkyl units can be regarded as structural elements, which differ from the structure of the isopropyl group by a –(CH2)n‐bridge (n = 1–4) between the two methyl groups. Furthermore, according to the natural interactions, the cyclopentyl group should be able to participate in the formation of van der Waals contacts in a similar way as that observed for the pyrrolidine ring of proline in some protein‐carbohydrate complexes. Such systematic binding studies allow the identification of interesting structure‐activity relationships, which are very useful for the development of artificial carbohydrate receptors with predictable binding properties.