6 páginas, 2 figuras, 2 esquemas, 2 tablas.-- ChemBioChem Special Issue: EMBO Symposium: Chemistry Meets Biology.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. On the basis of the experimental results, a structural model for trehalase inhibition by trehazolin and analogues is proposed, supported by theoretical calculations.Financial support by the Ministry of Science and Technology of Spain (project BQU2000-1501-C02-01) is gratefully acknowledged.Peer reviewed