Sulfonate derivatives, calixarenes

Direct synthesis of calixarenes with extended arms p-phenylcalix[4,5,6,8]arenes and their water-soluble sulfonated derivatives, M. Makha and C. L. Raston, Tetrahedron Lett., 2001, 42, 6215. 

The sulfonate derivatives (Fig. 4A), in which introduction of suitable ligand functions takes place at the para-position of the aromatic ring, are the most widely studied of the w ater-soluble calixarenes. Their solid-state binding to a wide range of metallic cations and complexes was reviewed by Raston and Atwood. The ability of these molecules to intercalate cations in expandable layers between bilayers of para-sulfonato-calix[4]arene led Atwood and Coleman in 1988 to name these systems Organic Clays." (Fig. 4C). Since then. Atwood extended the structural types observed to include liposomal analogues, tubes, and various Archimedian and Platonic solids."... 

In [51], Wacker oxidation of olefins was studied in the presence of catalytic systems comprising water-soluble calixarenes (sulfonated and glycydylated derivatives), palladium salt, and copper salt. The presence of nonpolar cavities in these molecules enables binding nonpolar substrates and their transfer into the aqueous phase where the reaction takes place. The activity of these catalysts depends on the complementarity between the cavity size of the host molecule and the size of the guest molecule. Therefore, substrate selectivity was exhibited. For example, the addition of calixarene increased the reaction rate for linear 1-alkenes which size corresponded to the size of the calixarene cavity (1-hexene for calix[4]arene and 1-octene for calix[6]arene). The activity of catalytic system applied for the oxidation of substituted styrenes also depended on the ratio of the size of the substrate molecule and that of the calixarene cavity. 

Although promiscuous in their choice of guest-compounds, the only well-defined catalytic system based upon the calixarenes, which has been documented, is the one described by Shinkai [61]. He has studied the acid-catalyzed addition of water (Scheme 6) to lV-benzyl-l,4-dihydronicotinamide in the presence of a para-sulfonatocalix[6]arene and its methoxycarbonyl derivative. The polyanionic nature of the upper rim, containing the sulfonate groups, provides a site for the stabilization of the cationic intermediate. The lower rim, which carries the phenolic... 

Upper rim substitution is typically more synthetically challenging than the lower rim, but can confer very useful properties on the macrocycle. For example, water soluble / -sulfonatocalixarenes have been synthesized and found to be highly water soluble, unlike the hydrophobic p-t-butyl derivatives. The sulfonated calixarenes form a variety of metal complexes where the metal is usually bound to the sulfonato groups of the calixarene. 

The p-sulfonatocalix[n]arenes 4, originally synthesized by Shinkai et al." as water soluble calixarenes for catalytic studies in water solution, were more recently used by Ueoka et alP as catalysts in the specific acid catalyzed methanolysis of A -Ac-L-amino acids (Phe, lyr, Trp, His, Lys, Arg). Rates of methanolysis in the presence of the calix[n] arene catalysts, normalized per sulfonic group, were compared with rates obtained in the presence of the noncyclic analogue p-hydroxybenzenesulfonic add. Rate enhancements - ranging from 12- to 86-fold - relative to control were recorded only in the methanolysis of basic amino acid derivatives (His, Lys, Arg), but neutral amino add derivatives (Phe, Tyr, Trp) responded virtually in the same way to the presence of cyclic and non-cyclic catalyst. Michaelis-Menten kinetics and H NMR spectral evidence pointed to the intermediacy of inclusion complexes of 4 with the protonated form of basic amino acid derivatives, as shown in 5 for the His-4 (n = 4) combination. 

Their application in the biomedical field is clearly demonstrated by the preponderance of patents as compared to publications in the field. Calixarenes functionalized at the wide rim with sulfonic acid and sulfonamide groups showed anticoagulant and antithrombotic properties, approaching the activity of heparin and coumarin, currently used as anticoagulants in antithrombotic therapy. Calixarene derivatives are also active as antiviral, antimicrobial. and antifungal agents. 

Recently, Sirit and co-workers [45] developed calixarene-based chiral phase-transfer catalysts derived from cinchona alkaloids successfully used for alkylation of glycine-imine esters. In 2010, Itsuno et al. [46] published quartemary ammonium sulfonate polymers used for a-alkylation reaction of a glycine imine ester with high yields and enantioselectivity. 

---