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 A₂ as well as heparan sulfate are highlighted.