Calixarenes Carbohydrates

Figure 6.10 Aggregation and lectin binding by multivalent calixarene carbohydrate-based receptors such as 6.32.14...

A. Dondoni, M. Kleban, X. Hu, A. Marra, and H. D. Banks, Glycoside-clustering round calixarenes toward the development of multivalent carbohydrate ligands. Synthesis and conformational analysis of calix[4]arene O- and C-glycoconjugates, J. Org. Chem., 67 (2002) 4722 -733. 

In summary, our approach of using cyclopeptides with natural amino acids and 3-aminobenzoic acid subunits for the development of macrocydic receptors has afforded remarkably efficient hosts. The cation affinity of 4b, for example, exceeds that of many calixarene derivatives. Even more interesting is the high anion affinity of 5 in aqueous solution. By introdudng additional functional groups such as car-boxylates to the periphery of the cavity, we recently also obtained cydopeptides that interact with neutral substrates, for example, carbohydrates [25]. Our peptides therefore represent a versatile dass of artificial receptor that should prove useful in supramolecular and bioorganic chemistry. 

The vancomycin mimics, 7, discussed above are an important example of biologically active calix[4]arene derivatives. In this case the whole macrobicy-clic structure including the calixarene skeleton with its cavity seems to be important for the pharmacological effect. In the following sections we discuss derivatives in which the calixarene serves more or less as an easily available scaffold for the assembly of biologically relevant fragments such as peptides or carbohydrates. 

Calixarene bis(phenylurea) McDonald 1998a Carbohydrates (all-atom)... 

Attachment of chiral substituents to calixarene skeleton is the first, the most straightforward and still the most popular way to constmct chiral calixarenes. In 1979 Gutsche reported the synthesis of the first chiral calixarene by attaching camphorosulfonyl group to p-tBu-calix[8]arene [1]. Nowadays, attachment of virtually any chiral moiety at the selected position is synthetically feasible. However, some chiral groups, due to their availability and versatility, have been particularly widely exploited, for example amino acid derivatives, peptides, carbohydrates, chiral amines and axially chiral groups. 

The calixarene family has proved to be an attractive scaffold for the development of both therapeutic molecules and delivery systems [1], Applications in a wide range of areas including cancer treatments, [2, 3] antivirals, [4] antibacterials, [5] and delivery of genes [6] and drugs [7] have been proposed. Of these, it is the calixsugars that have attracted the most attention where the combination of the carbohydrate and its presentation as a cluster lead to a variety of biological applications. 

Fig. 24.34 Left Calixarene-based glycocluster (R = H, R) oligonucleotide derivatives. Cy3 = fluorescent dye. Right Schematic representation of the hybridization assay for the investigation of lectin-carbohydrate interactions [102]. (Reprinted from Ref. [102])...

Our own involvement in carbohydrate recognition grew out of our interest in cholic acid as a building block for supramolecular chemistry. Having designed and synthesized the first cholaphane f> we were looking for an application. Prompted by the work of Aoyama on calixarene 17, the first synthetic carbohydrate receptor, we realised that the cavity of 16 was nicely complementary to a monosaccharide. H NMR... 

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