Semisynthetic aminoglycoside antibacterials. Part III. Synthesis of analogues of gentamicin X2 modified at the 3′-position

Abstract

In order to prevent inactivation of gentamicin X₂ by phosphorylation, a series of 3′-modified derivatives was prepared. These included 3′-deoxygentamicin X₂, O-2-amino-2-deoxy-α-D-allopyranosyl-(1 → 4)-garamine, and 3′-O-methylgentamicin X₂, all of which were synthesized by application of the Lemieux-Nagabhushan reaction, to a suitably protected garamine intermediate. The formation of O-2-amino-2-deoxy-3-O-methyl-β-D-manno-pyranosyl-(1 → 4)-garamine during the synthesis of 3′-O-methylgentamicin X₂ by the Lemieux-Nagabhushan reaction is reported. The solution conformations of the novel 4-O-β-D-mannopyranosyl and 4-O-β-D-glucopyranosyl derivatives are discussed. The formation of nitroglucals during the preparation of the nitroso-chloro-adducts is described.