A New Approach to 5‐Thiosugars: 5‐Thio‐ D ‐Gluconhydroximo‐1,5‐lactone, Synthesis and Evaluation as β‐Glucosidase Inhibitor

The thiolactone oxime 10 was synthesized in ten steps from the known tri‐ O ‐benzylglucose 13 , which was transformed into the oxime 14 , silylated (→ 15 ), and mesylated (→ 16 ). Treatment of 16 with Bu 4 NF yielded the L ‐ ido ‐epoxide 17 and the hydroxylamine 18 ; the isomeric D ‐ gluco ‐configurated hydroxylamine 20 was prepared from 17 . Reaction of 17 with thiourea yielded the thiirane 19 . Ring opening was best effected with HBr (→ 22 ·HBr). The N ‐glycosylhydroxylamine 22 was immediately oxidized to 24 , as it reverted to 19 . Similarly, 19 was transformed into the chlorides 21 and 23 . The iodide 25 reacted with TEMPO to afford 29 besides 26 and 30 ; nucleophilic substitution of 23 , 24 , or 25 gave unsatisfactory yields of 26 or 27 , and 28 . Birch reduction transformed 29 into 10 which was isolated via the pentaacetate 32 , which was also transformed into the tetraacetate 33 . The weak activity of 10 as an inhibitor of sweet‐almond and Agrobacter β‐glucosidase is in keeping with categorization of the lactone and lactam oximes 1–5 and the 5‐thiosugars 6–9 as transition‐state and substrate analogs, respectively.