Regioselective glycosylation of novobiocin alters activity

Abstract

Glycosylation is a promising approach to overcome antimicrobial drug resistance. In this study, we investigated Koenigs-Knorr and phase transfer glycosylation on novobiocin. While the former only gave a 4'-OH product, the later produced mainly a kinetic controlled 5-OH product, but still achieved the 4'-OH modification and novoise-glycosylated products (with stronger base), as well as a diglycosylated compound. Investigation on the antibacterial activity indicate that the presence of galactose moiety helps to improve activity possibly via enhanced cellular uptake.

Keywords: Antibacterial activity; Glycosylation; Novobiocin; Phase transfer reaction.