Synthesis of 6-sulfonatomethyl thioglycosides by nucleophilic substitution: Methods to prevent 1→6 anomeric group migration of thioglycoside 6-o-triflates

Article abstract of DOI:10.1002/ejoc.201300681

Introduction of a sulfonatomethyl moiety into the primary position of thioglycosides by nucleophilic displacement of the corresponding 6-O-triflate is described. The 1→6 migration of the anomeric group, which inevitably occurs through a bicyclic sulfonium ion intermediate, from conformationally flexible β-thioglycosides was prevented by using an α-thioglycoside or conformationally locked β-thioglycoside as the starting material. The thioglycoside 6-sulfonic acids showed excellent α-selectivity during synthesis of uronic acid containing heparinoid trisaccharides. Two routes to prepare C6-sulfonatomethyl thioglucosides by displacement of a 6-O-triflate moiety are reported. The undesired participation of the β-thio aglycon is prevented by changing the anomeric configuration or by locking the pyranose ring. The 6-sulfonatomethyl donors show excellent α-selectivities but significantly different reactivities during the synthesis of heparinoid trisaccharides. Copyright