Site-selective displacement of tobramycin hydroxyls for preparation of antimicrobial cationic amphiphiles.
A short site-selective strategy for the activation and derivatization of alcohols of the clinically important aminoglycoside tobramycin is reported. The choice of amine protecting group affected the site-selective conversion of secondary alcohols of tobramycin into leaving groups. Temperature-dependent, chemoselective sequential nucleophilic displacements resulted in hetero- and homodithioether tobramycin-based cationic amphiphiles that demonstrated marked antimicrobial activity and impressive membrane selectivity.
School of Chemistry, Raymond and Beverley Sackler Faculty of Exact Sciences, Tel Aviv University , Tel Aviv 69978, Israel.
Yifat
Y
Berkov-Zrihen
Ido M
IM
Herzog
Mark
M
Feldman
Micha
M
Fridman
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002236:Carbohydrate Conformation; D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006878:Hydroxides / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014031:Tobramycin / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D002412:Cations; D006878:Hydroxides; D014031:Tobramycin