US 4,060,682 A · Process for the synthetic production of 3-deoxy derivative of an aminoglycosidic antibiotic

Abstract

3'-Deoxy derivatives of neamine, 6'-N-alkylneamine, kanamycin B, 6'-N-alkylkanamycin B, ribostamycin, 6'-N-alkylribostamycin and paromamine may be produced by a new process comprising reducing the 3',4'-.alpha.-anhydro derivative (namely, the 3',4'-epoxide derivative) of the aminoglycosidic antibiotics with hydrogen in an alkaline lower alkanol medium containing an alkali metal hydroxide or alkoxide dissolved therein and in the presence of a reducing catalyst such as Raney nickel. The 3',4'-.alpha.-anhydro derivative may be prepared by treating the 3'-sulfonylated derivative of the amino-protected and hydroxyl-protected neamine, 6'-N-alkylneamine, kanamycin B, 6'-N-alkylkanamycin B, ribostamycin, 6'-N-alkylribostamycin or paromamine with an alkali metal hydroxide or alkoxide in a lower alkanol to effect epoxidation between the 4'-hydroxyl group and the carbon atom substituted by the 3'-sulfonic ester group.

Claims17

Dependent claims

A compound selected from the group consisting of 3',4'-.alpha.-anhydro derivatives of neamine or 6'-N-alkylneamine of the formula:

##STR19## wherein:
A and B are both hydrogen;
or A is hydrogen and B is a monovalent amino-protecting group selected from the group consisting of alkanoyl, alkoxycarbonyl, aryloxycarbonyl and arylmethoxycarbonyl of the formula --COR.sub.2 wherein R.sub.2 is hydrogen, lower alkyl, phenyl, lower alkoxy, phenoxy or benzyloxy;
or A and B taken together form a divalent amino-protecting group of the formula >CHR.sub.3 wherein R.sub.3 is hydrogen, lower alkyl or phenyl;
A' and B' are both hydrogen;
or A' is lower alkyl and B' is hydrogen;
or A' is hydrogen and B' is a monovalent amino-protecting group selected from the group consisting of alkanoyl, alkoxycarbonyl, aryloxycarbonyl and arylmethoxycarbonyl of the formula --COR.sub.2 wherein R.sub.2 has the above-indicated values;
and
Y represents two hydrogen atoms, cyclohexylidene, tetrahydropyranyl or a divalent hydroxyl-protecting group of the formula ##STR20## wherein P and P' are each hydrogen, alkyl of 1-4 carbon atoms, phenyl, p-methoxyphenyl or o-hydroxyphenyl.

6 more elements

A compound selected from the group consisting of 3',4'-.alpha.-anhydro derivatives of kanamycin B or 6'-N-alkylkanamycin B of the formula ##STR21## wherein:

A and B are both hydrogen;
or A is hydrogen and B is a monovalent amino-protecting group selected from the group consisting of alkanoyl, alkoxycarbonyl, aryloxycarbonyl and arylmethoxycarbonyl of the formula --COR.sub.2 wherein R.sub.2 is hydrogen, lower alkyl, phenyl, lower alkoxy, phenoxy or benzyloxy;
or A and B taken together form a divalent amino-protecting group of the formula >CHR.sub.3 wherein R.sub.3 is hydrogen, lower alkyl or phenyl;
A' and B' are both hydrogen;
or A' is lower alkyl and B' is hydrogen;
or A' is hydrogen and B' is a monovalent amino-protecting group selected from the group consisting of alkanoyl, alkoxycarbonyl, aryloxycarbonyl and arylmethoxycarbonyl of the formula --COR.sub.2 wherein R.sub.2 has the above-indicated values;
Y represents two hydrogen atoms, cyclohexylidene, tetrahydropyranyl or a divalent hydroxyl-protecting group of the formula ##STR22## wherein P and P' are each hydrogen, alkyl of 1-4 carbon atoms, phenyl, p-methoxyphenyl or o-hydroxyphenyl;
Z is hydrogen or alkanoyl of 2-5 carbon atoms;
and
Z' is hydrogen alkanoyl of 2-5 carbon atoms or benzyl.

7 more elements

A compound selected from the group consisting of 3',4'-.alpha.-anhydro derivatives of ribostamycin or 6'-N-alkylribostamycin of the formula:

##STR23## wherein:
A and B are both hydrogen;
or A is hydrogen and B is a monovalent amino-protecting group selected from the group consisting of alkanoyl, alkoxycarbonyl, aryloxycarbonyl and arylmethoxycarbonyl of the formula --COR.sub.2 wherein R.sub.2 is hydrogen, lower alkyl, phenyl, lower alkoxy, phenoxy or benzyloxy;
or A and B taken together form a divalent amino-protecting group of the formula >CHR.sub.3 wherein R.sub.3 is hydrogen, lower alkyl or phenyl;
A' and B' are both hydrogen;
or A' is lower alkyl and B' is hydrogen;
or A' is hydrogen and B' is a monovalent amino-protecting group selected from the group consisting of alkanoyl, alkoxycarbonyl, aryloxycarbonyl and arylmethoxycarbonyl of the formula --COR.sub.2 wherein R.sub.2 has the above-indicated values;
Y represents two hydrogen atoms, cyclohexylidene, tetrahydropyranyl or a divalent hydroxyl-protecting group of the formula ##STR24## wherein P and P' are each hydrogen, alkyl of 1-4 carbon atoms, phenyl, p-methoxyphenyl or o-hydroxyphenyl;
and
Z" and Z'" are each hydrogen or benzyl.

7 more elements

Dependencies are inferred from the claim text.

Process for the synthetic production of 3-deoxy derivative of an aminoglycosidic antibiotic

Life of this patent

Process for the synthetic production of 3-deoxy derivative of an aminoglycosidic antibiotic

Life of this patent

Abstract

Claims17