Synthesis of a fluorogenic substrate for alpha-L-iduronidase

Abstract

An alternative reaction pathway towards the preparation of an L-idopyranose derivative and its application to the synthesis of the alpha-L-iduronidase fluorogenic substrate 4-methylcoumarin-7-yl-alpha-L-iduronic acid as well as its 3-undecyl derivative are described. The L-ido sugar was prepared by converting the commercially available diacetone-alpha-D-glucose to methyl 1,2,3,4-tetra-O-acetyl-L-idopyranuronate via oxidation, esterification, and regioselective acetylation of the key intermediate 1,2:3,5-di-O-isopropylidene-beta-L-idofuranose. Mitsunobu-type glycosylation was employed in the coupling of the L-ido donor with the 4-methylcoumarin acceptors. This newly developed route reduced the difficulties previously encountered in the synthesis of the alpha-L-iduronidase fluorogenic substrate.