Glyco-optimization of aminoglycosides: new aminoglycosides as novel anti-infective agents.

Abstract Glyco-optimization (OPopS TM ) of aminoglycosides has been performed by replacing the existing sugar moiety with a variety of sugar derivatives. Glycosylation of the 6-position of nebramine provided a library of novel 4,6-linked aminoglycosides (AMGs). Among them, compounds 8b , g , i , l , and 8u with 2″-amino, 2″,3″-diamino, 2″,4″-diamino, 3″,4″-diamino, 3″-amino groups, respectively, showed significant antimicrobial activity against Gram-(+) and -(−) bacteria. Several were particularly potent against Pseudomonus aeruginosa with MICs in the 1–2 μg/mL range.