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Synthesis, Inhibition Properties, and Theoretical Study of the New Nanomolar Trehalase Inhibitor 1‐Thiatrehazolin: Towards a Structural Understanding of Trehazolin Inhibition
Author(s) -
Chiara Jose Luis,
Storch de Gracia Isabel,
García Ángela,
Bastida Ágatha,
Bobo Sofía,
MartínOrtega María D.
Publication year - 2005
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400231
Subject(s) - trehalase , chemistry , stereochemistry , nucleophile , intramolecular force , ring (chemistry) , ether , ketone , oxime , medicinal chemistry , enzyme , biochemistry , organic chemistry , catalysis
A new trehazolin analogue, 1‐thiatrehazolin, has been synthesized from carbohydrate precursors by a highly efficient route based on our previously developed ketone/oxime ether reductive carbocyclization reaction for the construction of the cyclitol ring and an intramolecular nucleophilic displacement reaction for the construction of the thiazoline ring. 1‐Thiatrehazolin is a very potent, slow, tight‐binding trehalase inhibitor. A structural model for trehalase inhibition by trehazolin and its analogues, based on the experimental results and supported by theoretical calculations, is proposed.