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Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β‐Galactosidase from E. coli
Author(s) -
Colomer Juan P.,
Canales Mayordomo María Ángeles,
Fernández de Toro Beatriz,
JiménezBarbero Jesús,
Varela Oscar
Publication year - 2015
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.201403609
Subject(s) - chemistry , diastereomer , stereochemistry , stereocenter , sulfur , substrate (aquarium) , hydrolysis , enzyme , thio , absolute configuration , conformational isomerism , medicinal chemistry , organic chemistry , catalysis , enantioselective synthesis , molecule , oceanography , geology
Benzyl 3‐deoxy‐4‐ S ‐(β‐ D ‐galactopyranosyl)‐4‐thio‐β‐ D ‐ threo ‐pentopyranoside ( 3 ) is a potent inhibitor of the β‐galactosidase from Escherichia coli synthesized in our laboratory. The 2′,3′,4′,6′‐tetra‐ O ‐acetyl derivative of this thiodisaccharide was oxidized with m ‐chloroperoxybenzoic acid to give a 2:1 diastereomeric mixture of sulfoxides 2 S and 2 R . The absolute configurations of their sulfur stereocenters were determined by using NMR techniques and by taking into account the anisotropic effects of the S=O group in the major conformers. O ‐Deacetylation of 2 S and 2 R afforded the free thiodisaccharide S ‐oxides 4 S and 4 R , which were evaluated as inhibitors of the above‐mentioned enzyme. The kinetic studies showed that 4 S and 4 R are competitive inhibitors of the enzyme with K i values of 0.19 and 0.45 m M , respectively. Further enzymatic reactions demonstrated that 4 S is also a substrate of the β‐galactosidase, as it was diastereoselectively hydrolyzed, with 4 R remaining unchanged under the same conditions.