Remarkable Supramolecular Catalysis of Glycoside Hydrolysis by a Cyclodextrin Cyanohydrin

(6A R,6D R)-6A,6D-di-C-cyano-β-cyclodextrin (3) was synthesized and shown to catalyze hydrolysis of nitrophenyl glycosides with the reaction following Michaelis−Menten kinetics. At pH 7.4 and 25 °C, hydrolysis of 4-nitrophenyl-β-glucopyranoside (2) was catalyzed with K M = 15 mM, k cat = 8.2 × 10-6 s-1, and k cat/k uncat = 1217. Catalysis was observed with concentration of 3 as low as 10 μM. Hydrolysis of the corresponding α-glucoside, α-galactoside, α-mannoside, and 2-nitrophenyl-β-galactoside was also catalyzed by 3, with k cat/k uncat ranging from 283 to 2147. A series of analogues of 3 was prepared and investigated for catalysis of the hydrolysis of 2: (6A R,6D R)-6A,6D-di-C-propyl-β-cyclodextrin (9) was not catalytic, while 6A,6D-di-C-cyano-6A,6D-dideoxy-β-cyclodextrin (12) had a low catalytic activity (k cat/k uncat = 4). A k cat/k uncat = 48 was found for 6A,6D-dialdehydo-β-cyclodextrin dihydrate (11). It was proposed that 3 acts by general acid catalysis on the bound substrate.