Cyanodeoxy‐Glycosyl Derivatives as Substrates for Enzymatic Reactions

Abstract

Synthetic routes for the preparation of new sugar nitriles 8–10 derived from 2‐acetamido‐2‐deoxy‐β‐D‐glucopyranosides bearing a cyano group at the C‐5 or C‐6 position are presented. In an attempt to prepare the glycosyl azide 10 by treatment of tosylate 23 with KCN/DMF at 60 °C, an intramolecular 1,3‐dipolar cycloaddition reaction occurred to give the highly constrained nonisolable tetrazole 24, which was readily converted into the imino‐azido compound 25 through an azido‐tetrazole tautomerism. Compounds 8 and 10 werefound to be poorer substrates of fungal β‐N‐acetylhexosaminidases than compound 9 and none of these compounds was accepted as substrates of the nitrilase or nitrile hydratase. Docking of the nitriles 8–10 in the active site of the β‐N‐acetylhexosaminidase from Aspergillus oryzae gave interaction energies comparable with the natural substrate. Based on these data, which indicate strong binding of these compounds (8 > 9 > 10) to the active site, it has been proposed that some cyano derivatives may act as competitive inhibitors of β‐N‐acetylhexosaminidases. This hypothesis is consistent with enzyme inhibition experiments which showed strong inhibitory properties of compound 9 (KI = 0.37 mM) and in particular of compound 8 (KI = 7.6 μM). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Computational study of β-N-acetylhexosaminidase from Talaromyces flavus, a glycosidase with high substrate flexibility

“…Additionally to their primary hydrolytic activity, these enzymes have been shown to catalyze transglycosylation reactions, where a carbohydrate moiety is transferred from an activated sugar donor to its acceptor, typically an alcohol or a carbohydrate, which makes them a good alternative to glycosyltransferases due to high regioselectivity and lower cost of the substrates [ 2 ]. Amongst the hexosaminidase family, the enzymes obtained from filamentous fungi, especially those from the Aspergillus , Penicillium and Talaromyces genera, have proved a great potential in the synthetic reactions, moreover, they have shown enormous substrate flexibility by accepting a variety of unnatural substrates [ 3 - 7 ]. The β- N -acetylhexosaminidase from Talaromyces flavus CCF2686 has found its prominent position within the fungal enzymes with its extraordinary results in the transglycosylation reactions with the 4-deoxy-substrates [ 8 ] and C-6 oxidized and negatively charged substrates [ 9 ].…”

Cyanodeoxy‐Glycosyl Derivatives as Substrates for Enzymatic Reactions

“…In Scheme 3 on page 1879 of the original article, 1 the configuration of the bis‐acetal centers of compounds 24 and 25 should be (S,S) instead of (R,R); the correct drawings of these formulae are shown below (the atom numbering does not correspond to the IUPAC nomenclature numbering). In addition, the correct name of compound 25 on page 1883 is:…”