Synthesis of 4‐Epoxy‐4‐ c ‐methyleneglycosylceramides, Potential Glycosyltransferase Inhibitors

D ‐Glucose was transformed into the 4‐deoxy‐4‐ C ‐methylene derivative 1 . Dihydroxylation of 1 and then selective O ‐tosylation afforded 4‐ C ‐(tosyloxymethyl)glucoside 3 . Subsequent hydrogenolytic O ‐debenzylation, selective O ‐acetylation, treatment with a base, selective removal of the anomeric O ‐acetyl group, and then treatment with trichloroacetonitrile in the presence of a base furnished 4‐epoxy‐4‐ C ‐methyleneglucosyl donor 7 (α,β mixture). Reaction of 7 with 3‐ O ‐acyl‐protected azidosphingosines 8a – c in the presence of Et 2 O.BF 3 gave β‐glycosides 9a – c . Compounds 9a – c were transformed into the corresponding glucosylceramide derivatives 10a – c by treatment with triphenylphosphane/water and acyl anhydrides. Satisfactory removal of the O ‐benzoyl protective group was difficult; however, O ‐acetyl and O ‐isobutyryl protective groups could be removed by methanolysis, thus affording from 10b , c the target molecules 11 and 12 with varying alkyl‐chain length. The epoxide 16 with galacto configuration, readily obtained from 1 , on treatment with p ‐toluenesulfonic acid furnished 4‐ C ‐(tosyloxymethyl)galactoside 18 ; this was transformed, as outlined for 3 , into the target molecules 25b , c having galacto configuration in the sugar moiety.