Remarkable Supramolecular Catalysis of Glycoside Hydrolysis by a Cyclodextrin Cyanohydrin

• Published in: Journal of the American Chemical Society 2005-03, Vol.127 (10), p.3238-3239
• Main Authors: Ortega-Caballero, Fernando, Rousseau, Cyril, Christensen, Brian, Petersen, Torben Ellebæk, Bols, Mikael
• Format: Article
• Language: English
• Subjects: Biomimetic Materials - chemical synthesis; Biomimetic Materials - chemistry; Catalysis; Chemistry; Cyclodextrins - chemical synthesis; Cyclodextrins - chemistry; Exact sciences and technology; Glycoside Hydrolases - chemistry; Glycoside Hydrolases - metabolism; Glycosides - chemistry; Glycosides - metabolism; Hydrolysis; Kinetics; Kinetics and mechanisms; Nitriles - chemical synthesis; Nitriles - chemistry; Organic chemistry; Reactivity and mechanisms
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja042678a

(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.