Functionalized cyclodextrins as holoenzyme mimics of thiamine-dependent enzymes

Abstract

Mimics of vitamin B 1-dependent enzymes have been prepared by covalently linking thiazolium salts to the primary side of β-cyclodextrin. Although these compounds were found to catalyze the benzoin condensation, they were generally less effective turnover catalysts than the analogous simple thiazolium salts lacking the artificial binding site. An improvement in the design of the sugar derivative which prevented competitive binding of the thiazolium moiety to the cyclodextrin cavity did, however, lead to a superior catalyst of this transformation. In catalytic processes which required only one molecule of substrate to react with the thiazolium salt, rate accelerations, saturation kinetics, and substrate selectivity were observed. Thus, all the cyclodextrin thiazolium salts speeded the rate of tritium exchange from suitably labeled aromatic aldehydes more than did simple thiazolium salts. In addition, rate enhancements of up to ca 40-fold were observed for the thiazolium-catalyzed oxidation of tert-butylbenzaldehyde by ferricyanide compared with a thiazolium salt lacking the cyclodextrin binding group.