From D‐Glucose to Biologically Potent L‐Hexose Derivatives: Synthesis of α‐L‐Iduronidase Fluorogenic Detector and the Disaccharide Moieties of Bleomycin A2 and Heparan Sulfate

Abstract A novel and convenient route for the synthesis of biologically potent and rare L ‐hexose derivatives from D ‐glucose is described. Conversion of diacetone‐α‐ D ‐glucose ( 14 ) into 1,2:3,5‐di‐ O ‐isopropylidene‐β‐ L ‐idofuranose ( 19 ) was efficiently carried out in two steps. Orthogonal isopropylidene rearrangement of compound 19 led to 1,2:5,6‐di‐ O ‐isopropylidene‐β‐ L ‐idofuranose ( 27 ), which underwent regioselective epimerization at the C3 position to give the L ‐talo‐ and 3‐functionalized L ‐idofuranosyl derivatives. Hydrolysis of compound 19 under acidic conditions furnished 1,6‐anhydro‐β‐ L ‐idopyranose ( 35 ) in excellent yield, which was successfully transformed into the corresponding L ‐ allo , L ‐ altro , L ‐ gulo , and L ‐ ido derivatives via regioselective benzylation, benzoylation, triflation and nucleophilic substitution as the key steps. Applications of these 1,6‐anhydro‐β‐ L ‐hexopyranoses as valuable building blocks to the syntheses of 4‐methylcoumarin‐7‐yl‐α‐ L ‐iduronic acid and the disaccharide moieties of bleomycin A 2 as well as heparan sulfate are highlighted.