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Site-selective displacement of tobramycin hydroxyls for preparation of antimicrobial cationic amphiphiles
Yifat Berkov-Zrihen1, Ido M Herzog, Mark Feldman
1School of Chemistry, Raymond and Beverley Sackler Faculty of Exact Sciences, Tel Aviv University , Tel Aviv 69978, Israel.
Abstract:
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.
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