Synthesis of L-idaro-1,4-lactone, an inhibitor of alpha-L-idosiduronase

L-idaro-1,4-lactone was synthesized by two different, published methods: (1) epimerization of monopotassium D-glucarate by refluxing in aqueous barium hydroxide, and (2) oxidation of L-iditol by heating in dilute nitric acid. The lactone, formed by heat dehydration from aqueous solution at low pH, was purified by paper chromatography, and quantitated by gas-liquid chromatography using inositol as the internal standard. The monolactone inhibited human, seminal-fluid alpha-L-idosiduronase activity, with either phenyl or 4-methylumbelliferyl alpha-L-idosiduronic acid as the substrate, to the same degree as D-glucaro-1,4-lactone inhibits alpha-D-glucosiduronase.