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Cyanodeoxy‐Glycosyl Derivatives as Substrates for Enzymatic Reactions
Author(s) -
Carmona Ana T.,
Fialová Pavla,
Křen Vladimir,
Ettrich Rudiger,
Martínková Ludmila,
MorenoVargas Antonio J.,
González Cristina,
Robina Inmaculada
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200500755
Subject(s) - chemistry , tetrazole , glycosyl , cycloaddition , azide , nitrile , stereochemistry , nitrilase , hydrazone , docking (animal) , tautomer , intramolecular force , substrate (aquarium) , active site , enzyme , organic chemistry , catalysis , medicine , oceanography , nursing , geology
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 ( K I = 0.37 m M ) and in particular of compound 8 ( K I = 7.6 μ M ). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)