Synthesis of vancomycin from the aglycon

Vancomycin-resistant bacterial strains pose a serious threat to human healt h. Efforts to overcome vancomycin resistance by modifying the natural produ ct have shown that the carbohydrates help modulate biological activity. To explore the mechanisms by which the carbohydrates function, it would be use ful to have access to vancomycin derivatives containing different disacchar ides. We now describe the synthesis of vancomycin from a readily available protected aglycon. This chemistry lays the groundwork for wide-ranging inve stigations of the roles of the carbohydrates in the biological activity of vancomycin. Moreover, in developing methods to glycosylate vancomcyin, we h ave extended the utility of the sulfoxide glycosylation reaction considerab ly by making it possible to use unhindered esters as neighboring groups. Th e chemistry we describe may also have implications for how to improve some other glycosylation methods.