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 Bu₄NF 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.