Benzamidine receptor

A Benzamidine Receptor. Cationic aromatic guests may bind to synthetic receptors by a combination of hydrogen-bonding and jc-stacking interactions. Figure 11 displays the complex of benzamidinium chloride with a hexagonal lattice cleft that is bridged by an aromatic spacer unit (27). Results of titration studies in 95 5... 

Schematically shown in Fig. 5 is the preparation of an enzyme mimic for the hydrolysis of ester 6 by molecular imprinting. Phosphonate 5 is an analog of the transition state for the alkaline hydrolysis of Ester 4. It was used as a template for polymerization with two equivalents of the binding-site monomer iVJV -diethyl-4-vinyl-benzamidine. Amidinium groups were chosen, because they can interact electrostatically with the side carboxyl-ate group as well as with the anionic transition state of the alkaline hydrolysis, thus achieving substrate recognition and transition-state stabilization. Polymerization of the preassembled binding-site monomer with the template (Fig. 5A) followed by template removal (Fig. 5B) leaves a cavity that acts as transition-state receptor for the ester substrate (Fig. 5C). The imprinted polymer accelerates the hydrolysis of 6 more than 100-fold compared to the reaction at the same pH in buffer solution without the polymer. The reaction kinetics is of the Michaelis-Menten type. A polymer obtained with amidinium benzoate as a control, with a statistical distribution of amidinium groups, is ca. one order of magnitude less active in the hydrolysis of 6.

The Schollkopf reaction has found considerable use in the preparation of eompounds containing 4,5-disubstituted oxazoles. 4,5-Disubstituted oxazole 30 served as a key intermediate in DuPont s synthesis of benzamidine 31, a Factor Xa inhibitor. The Sehdllkopf reaetion has similarly found use in the preparation of 4,5-disubstituted oxazoles for P3-adrenergie receptor agonist," Fe(II)-form-selective E. coli methionine aminopeptidase inhibitor," and prostacyclin receptor antagonist programs. The robustness of this synthetic methodology has also led to the use of the Schollkopf oxazole synthesis as a test reaction in the evaluation of a number of flow-reactor systems. ... 

---