Schering Corporation

William N Turner

Alan B Cooper

Tattanahalli L Nagabhushan

Peter J Daniels

Described are transition metal salt complexes of available neighboring amino and hydroxyl group pairs in polyamino organic compounds, their preparation, and use as intermediates in the preparation of selectively N-blocked polyamino organic compounds.

Transition metal salt complexes of polyamino organic compounds

Selective blocking of some amino groups in a polyamino organic compound having at least one pair of available neighboring hydroxyl and amino groups is effected by first preparing in situ transition metal salt complexes of available neighboring amino and hydroxyl group pairs in said polyamino organic compound, followed by introduction of blocking groups on the non-complexed amino groups and, finally, removing the transition metal cations from the selectively N-blocked polyamino organic compound complex to obtain a polyamino organic compound having selectively blocked amino groups. This process is particularly valuable when carrying out aminocyclitol-aminoglycoside transformations utilizing transition metal salt complexes of cupric acetate, nickel (II) acetate, cobalt (II) acetate or mixtures thereof.

Aminoglycoside antibiotic compounds

Process of selectively blocking amino functions in aminoglycosides using

Described are 6'-N-alkyl derivatives of antibacterially active 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols having a primary carbinamine at C-5' of which a preferred group are 6'-N-alkyl derivatives having 2 to 4 carbon atoms of 4-O-aminoglycosyl-6-O-garosaminyl-2-deoxystreptamines having a primary carbinamine at C-5', a particularly preferred compound being 6'-N-ethylsisomicin. The 6'-N-alkyl derivatives are prepared by the reaction of the corresponding 6'-N-unsubstituted aminoglycoside having protecting groups on all other amino functions with an aldehyde or a ketone, followed by the reaction in situ of the 6'-N-substituted intermediate thereby formed with a hydride reducing agent, then removal of any N-protecting groups. Pharmaceutical formulations comprising 6'-N-alkylaminoglycosides of the invention are described and the method for their use in treating bacterial infections.

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Bloomfield, NJ, United States of America

William N Turner