Job/Unit: O20699 /KAP1 Date: 13-08-12 11:47:02 Pages: 8 FULL PAPER DOI: 10.1002/ejoc.201200699 Two Diastereomeric Artificial Enzymes with Different Catalytic Activity Emil Lindbäck, [a] You Zhou, [a] Christian Marcus Pedersen, [a] and Mikael Bols* [a] Keywords: Cyclodextrins / Glycosides / Enzyme mimics / Hydrolysis / Oxidation Two epimeric cyclodextrin-6-C-aldehydes were synthesised in 10 steps from β-cyclodextrin. The synthesis involved pro- tection/partial deprotection, oxidation to a 6-aldehyde, ole- fination, dihydroxylation, selective protection of the second- ary alcohol and oxidation. The two isomers catalysed the oxidation of aromatic amines by hydrogen peroxide but pre- Introduction Catalysis is a field of growing importance as the demand for green and sustainable processes continues to increase. The most sophisticated form of catalysis, enzyme catalysis, is performed by naturally occurring proteins, and an ex- tremely small number of small organic molecules, [1] most of which are cyclodextrin derivatives. [2] Although these artifi- cial enzymes are less efficient catalysts than natural enzymes at present, promising rate increases of over 6  10 4 suggest that this is a matter of proper adjustment of the artificial enzyme structure. [3] Recently, we found that cyclodextrin-6-aldehydes, such as 1 (Figure 1), were very good catalysts of the oxidation of aromatic amines and alcohols by hydrogen peroxide. [4] The reactions occur by the addition of H 2 O 2 to the aldehyde followed by a more facile oxidation of the aromatic sub- strate that is bound in the cyclodextrin cavity. The rate in- creases obtained are 10 3 –10 4 times faster than the uncata- lysed reaction, which is better than some natural oxidases. [5] We wished to improve these promising catalysts and a possible way of doing so would be to move the catalytic group closer to the bound substrate by, for example, chain extension at C-6. It is important that the aldehyde has little conformational freedom, as a catalyst with many possible conformers will be poor for the simple reason that only a small fraction of the compound is in the catalytic confor- mation. However, we have previously found that rigidity is maintained when one extends the C chain at the 6-position provided that the hydroxy group is retained. [6,7] Therefore, [a] Department of Chemistry, University of Copenhagen, Universitetsparken 5, Denmark Fax: +45-35320214 E-mail: bols@chem.ku.dk Homepage: www.ki.ku.dk Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejoc.201200699 Eur. J. Org. Chem. 0000, 0–0 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1 dominantly outside the cavity. Hydrolysis of aryl glycosides on the other hand was catalysed in a reaction following Michaelis–Menten kinetics. The S isomer was a 5–20 times better catalyst than the R isomer, which was explained from models. Figure 1. Cyclodextrin-6-aldehydes. extension with one carbon atom to the α-methoxy alde- hydes 2R and 2S was an obvious choice (Figure 1) as the methoxy group was expected to behave in a similar manner to an OH group due to the similarity in electronic effects. We report the synthesis of these two compounds and the study of their performance as enzymatic catalysts of various reactions.