A β-d-glucosidase inhibitor, cyclophellitol [(1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4.1.0]heptane-2,3,4-triol, 1] and its epoxide diastereomer, 1,6-epicyclophellitol (2) have been synthesized by using an intramolecular [3+2]-cycloaddition of a nitrile oxide to an alkene as a key step. 2,3,4-Tri-O-benzyl-6,7-dideoxy-d-ido-hept- 6-enose (E,Z)-oxime (6) was prepared from l-glucose in 11 steps. Intramolecular cycloaddition of 6 was realized by NaOCl via an intermediary nitrile oxide to afford the isoxazoline, (1S,2R,3S,4S,5R)-3,4,5-tribenzyloxy-2-hydroxy-8-oxa-7-azabicyclo[4.3.0]non-6-ene (7). Hydrogenolysis of 7 followed by a 5-step sequence gave cyclophellitol (1). Compound 2 was synthesized from methyl δ-d-galactopyranoside by using a conceptually similar route. The glycosidase-inhibiting activities of 2 were examined.
ASJC Scopus subject areas