Production of a selectively protected n-acylated derivative...

C - Chemistry – Metallurgy – 07 – H

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C07H 15/22 (2006.01)

Patent

CA 1131628

- 1 - THE PRODUCTION OF A SELECTIVELY PROTECTED N-ACYLATED DERIVATIVE OF AN AMINOGLYCOSIDIC ANTIBIOTIC ABSTRACT OF THE DISCLOSURE Aminoglycosidic antibiotic comprising a 6-0-(3"- aminoglycosyl)-2-deoxystreptamine optionally having a 4-0- (aminogycosyl) group, such as kanamycins, gentamicins, sisomicin, forms reversible complex with zinc cations by association of the zinc cations with some pairs of amino hydroxyl groups in the aminoglycoside, and the zinc-complexed amino groups are blocked from acylation. Reaction of this zinc complex with an acylation reagent having an amino- blocking acyl group brings about acylation of the non-complexed amino groups to give an N-acylated zinc complex, namely a complex of zinc cation with an N-acylated aminoglycosidic antibiotic derivative. Removal of zinc cations from N- acylated zinc complex yields a partially N-acylated amino- glycosidic antibiotic where 1- and 3"-amino groups are unprotected but all other amino groups protected with acyl group. Further reaction of this partially N-acylated product with a certain alkanoic acid or N-formyl-imidazole results in preferential acylation of 3"-amino group without 1-amino group being acylated, affording a 1-N-unprotected and other N-fully-protected derivative of the aminoglycosidic antibiotic which is valuable to be 1-N-acylated with .alpha.-hydroxy-.omega.-amino- alkanoic acid for high-yield production of known semi-synthetic 1-N-(.alpha.-hydroxy-.omega.-aminoalkanoyl)-aminoglycosidic antibiotic.

386540

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