Boron-mediated aglycon delivery for late-stage modifications: applications in chemical biology and pharmaceutical lead development

Abstract The stereoselective synthesis of 1,2-cis glycosides, which are essential structural motifs in bioactive molecules, remains a significant challenge. This review highlights recent advancements in boron-mediated aglycon delivery (BMAD)—a novel regio- and 1,2-cis-stereoselective glycosylation approach for unprotected glycosides. The efficacy of BMAD is demonstrated through the late-stage modification of complex biomolecules, including lanatoside C, enabling target protein identification. The synthesis of novel azithromycin derivatives yielded a new lead compound with enhanced anti-mycobacterial activity, attributed to a distinct ribosome binding mechanism.