5-epi-4,6-di-o-(aminoglycosyl)-2-deoxystreptamines, methods for their manufacture and intermediates useful therein, methods for their use as antibacterial agents and compositions useful therefor

Claim 2

A compound selected from the group consisting of a 5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine selected from the group consisting of 5-epigentamicin A, 5-epigentamicin B, 5-epigentamicin B 1 , 5-epigentamicin C 1 , 5-epigentamicin C 1a , 5-epigentamicin C 2 , 5-epigentamicin C 2a , 5-epigentamicin C 2b , 5-epigentamicin X 2 , 5-epitobramycin, 5-epiverdamicin, 5-epikanamycin A, 5-epikanamycin B, 5-epi-3',4'-dideoxykanamycin B, 5-epi-Antibiotic G-52, 5-epi-Antibiotic 66-40B, 5-epi-Antibiotic 66-40D, 5-epi-Antibiotic G-418, 5-epi-Antibiotic JI-20A, 5-epi-Antibiotic JI-20B; the 1-N-K-derivatives of the foregoing, wherein K is an alkyl substituent selected from the group consisting of alkyl, alkyl cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 8 carbon atoms, the carbon in said alkyl substituent adjacent to the aminoglycoside nitrogen being unsubstituted, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only one of said functions can be attached at any one carbon atom; and the pharmaceutically acceptable acid addition salts thereof.

Claim 3

A compound of claim 1 wherein said 5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine is a 5-epi-4-O-aminoglycosyl-6-O-garosaminyl-2-deoxystreptamine.

Claim 4

A compound of claim 2 which is 5-epigentamicin B.

Claim 5

A compound of claim 2 which is 5-epigentamicin B 1 .

Claim 6

A compound of claim 2 which is 5-epigentamicin C 1 .

Claim 7

A compound of claim 2 which is 5-epigentamicin C 1a .

Claim 8

A compound of claim 2 which is 5-epigentamicin C 2 .

Claim 9

A compound of claim 2 which is 5-epigentamicin C 2a .

Claim 10

A compound of claim 2 which is 5-epigentamicin C 2b .

Claim 11

A compound of claim 2 which is 5-epigentamicin X 2 .

Claim 12

A compound of claim 2 which is 5-epiverdamicin.

Claim 13

A compound of claim 2 which is 5-epi-Antibiotic G-52.

Claim 14

A compound of claim 2 which is 5-epi-Antibiotic G-418.

Claim 15

A compound of claim 2 which is 5-epi-Antibiotic JI-20A.

Claim 16

A compound of claim 2 which is 5-epi-Antibiotic JI-20B.

Claim 17

A compound of claim 1 which is 5-epi-Antibiotic 66-40D.

Claim 18

A 1-N-K derivative of claim 1 wherein K is an alkyl substituent having up to 4 carbon atoms.

Claim 19

A 1-N-K derivative of claim 1 wherein K is ethyl.

Claim 20

A compound selected from the group consisting of a 1-N-acyl derivative of a 5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine selected from the group consisting of 5-epigentamicin A, 5-epigentamicin B, 5-epigentamicin B 1 , 5-epigentamicin C 1 , 5-epigentamicin C 1a , 5-epigentamicin C 2 , 5-epigentamicin C 2a , 5-epigentamicin C 2b , 5-epigentamicin X 2 , 5-epitobramycin, 5-epiverdamicin, 5-epikanamycin A, 5-epikanamycin B, 5-epi-3',4'-dideoxykanamycin B, 5-epi-Antibiotic G-52, 5-epi-Antibiotic 66-40B, 5-epi-Antibiotic 66-40D, 5-epi-Antibiotic G-418, 5-epi-Antibiotic JI-20A, 5-epi-Antibiotic JI-20B; wherein said acyl is ##STR25## with K' being hydrogen or an alkyl substituent selected from the group consisting of alkyl, cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 7 carbon atoms, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only one of said functions can be attached at any one carbon atom; and the acid addition salts thereof.

Claim 21

A compound selected from the group consisting of a 1-N-acyl derivative of a 5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine selected from the group consisting of 5-epigentamicin A, 5-epigentamicin B, 5-epigentamicin B 1 , 5-epigentamicin C 1 , 5-epigentamicin C 1a , 5-epigentamicin C 2 , 5-epigentamicin C 2a , 5-epigentamicin C 2b , 5-epigentamicin X 2 , 5-epitobramycin, 5-epiverdamicin, 5-epikanamycin A, 5-epikanamycin B, 5-epi-3',4'-dideoxykanamycin B, 5-epi-Antibiotic G-52, 5-epi-Antibiotic 66-40B, 5-epi-Antibiotic 66-40D, 5-epi-Antibiotic G-418, 5-epi-Antibiotic JI-20A, 5-epi-Antibiotic JI-20B; wherein said acyl is ##STR25## with K' being hydrogen or an alkyl substituent selected from the group consisting of alkyl, cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 7 carbon atoms, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only one of said functions can be attached at any one carbon atom; and the acid addition salts thereof.

Claim 22

A compound of claim 19 wherein said 1-N-acyl is 1-N-acetyl.

Claim 23

The process for preparing a 5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine selected from the group consisting of 5-epigentamicin A, 5-epigentamicin B, 5-epigentamicin B 1 , 5-epigentamicin C 1 , 5-epigentamicin C 1a , 5-epigentamicin C 2 , 5-epigentamicin C 2a , 5-epigentamicin C 2b , 5-epigentamicin X 2 , 5-epitobramycin, 5-episisomicin, 5-epiverdamicin, 5-epikanamycin A, 5-epikanamycin B, 5-epi-3',4'-dideoxykanamycin B, 5-epi-Antibiotic G-52, 5-epi-Antibiotic 66-40B, 5-epi-Antibiotic 66-40D, 5-epi-Antibiotic G-418, 5-epi-Antibiotic JI-20A, 5-epi-Antibiotic JI-20B; and the 1-N-K derivatives thereof, wherein K is an alkyl substituent selected from the group consisting of alkyl, alkyl cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 8 carbon atoms, the carbon in said alkyl substituent adjacent to the aminoglycoside nitrogen being unsubstituted, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only one of said functions can be attached at any one carbon atom; which comprises the reaction of the corresponding 5-O-R-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine wherein R is a hydrocarbonsulfonyl or a halogeno derivative thereof, said hydrocarbon having up to 8 carbon atoms, or a nitrobenzenesulfonyl; and wherein all other hydroxyl functions and all amino functions are protected by groups susceptible to reductive cleavage or to basic or mild acid hydrolysis; with dimethylformamide at temperatures in the range of from about 80° C to about 155° C; followed by removal of the protecting groups in the resulting N-protected-O-protected intermediate with aqueous base or, when protecting groups susceptible to reductive cleavage are present, by reaction of said resulting intermediate with hydrogen in the presence of a catalyst or with an alkali metal in liquid ammonia, followed by treatment with aqueous base; thence, when any of said protecting groups are acetals or ketals, reaction of the resulting O-protected intermediate with aqueous acid.

Claim 24

The process for preparing a 5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine selected from the group consisting of 5-epigentamicin A, 5-epigentamicin B, 5-epigentamicin B 1 , 5-epigentamicin C 1 , 5-epigentamicin C 1a , 5-epigentamicin C 2 , 5-epigentamicin C 2a , 5-epigentamicin C 2b , 5-epigentamicin X 2 , 5-epitobramycin, 5-episisomicin, 5-epiverdamicin, 5-epikanamycin A, 5-epikanamycin B, 5-epi-3',4'-dideoxykanamycin B, 5-epi-Antibiotic G-52, 5-epi-Antibiotic 66-40B, 5-epi-Antibiotic 66-40D, 5-epi-Antibiotic G-418, 5-epi-Antibiotic JI-20A, 5-epi-Antibiotic JI-20B; and the 1-N-K derivatives thereof, wherein K is an alkyl substituent selected from the group consisting of alkyl, alkyl cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 8 carbon atoms, the carbon in said alkyl substituent adjacent to the aminoglycoside nitrogen being unsubstituted, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only one of said functions can be attached at any one carbon atom; which comprises the reaction of the corresponding 5-O-R-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine wherein R is a hydrocarbonsulfonyl or a halogeno derivative thereof, said hydrocarbon having up to 8 carbon atoms, or a nitrobenzenesulfonyl; and wherein all other hydroxyl functions and all amino functions are protected by groups susceptible to reductive cleavage or to basic or mild acid hydrolysis; with dimethylformamide at temperatures in the range of from about 80° C to about 155° C; followed by removal of the protecting groups in the resulting N-protected-O-protected intermediate with aqueous base or, when protecting groups susceptible to reductive cleavage are present, by reaction of said resulting intermediate with hydrogen in the presence of a catalyst or with an alkali metal in liquid ammonia, followed by treatment with aqueous base; thence, when any of said protecting groups are acetals or ketals, reaction of the resulting O-protected intermediate with aqueous acid.

Claim 25

The process of claim 21 wherein R is methanesulfonyl.

Claim 26

The process of claim 21 when carried out in the presence of a tetraalkylammonium alkanoate.

Claim 27

The process of claim 21 when carried out in the presence of tetra-n-butylammonium acetate.

Claim 28

The process for preparing a 5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine selected from the group consisting of 5-epigentamicin A, 5-epigentamicin B, 5-epigentamicin B 1 , 5-epigentamicin C 1 , 5-epigentamicin C 1a , 5-epigentamicin C 2 , 5-epigentamicin C 2a , 5-epigentamicin C 2b , 5-epigentamicin X 2 , 5-epitobramycin, 5-epiverdamicin, 5-episisomicin, 5-epikanamycin A, 5-epi-3',4'-dideoxykanamycin B, 5-epi-Antibiotic G-52, 5-epi-Antibiotic 66-40B, 5-epi-Antibiotic 66-40D, 5-epi-Antibiotic G-418, 5-epi-Antibiotic JI-20A, 5-epi-Antibiotic JI-20B; and the 1-N-K-derivatives of the foregoing, wherein K is an alkyl substituent selected from the group consisting of alkyl, alkyl cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 8 carbon atoms, the carbon in said alkyl substituent ajacent to the aminoglycoside nitrogen being unsubstituted, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only one of said functions can be attached at any one carbon atom; which comprises the reaction of the corresponding 4,6-di-O-(aminoglycosyl)-2-deoxystreptamine wherein the amino functions and hydroxyl functions other than the 5-hydroxyl function are protected by groups susceptible to reductive cleavage or to basic or mild acid hydrolysis, with an oxidizing agent selected from the group consisting of ruthenium tetroxide, chromic acid in acetone, or chromium trioxide-pyridine complex in methylene chloride; the reaction of the resulting N-protected-O-protected-5-dehydro-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine with an alkali metal borohydride; followed by removal of the protecting groups by treatment of the thereby produced N-protected-O-protected-5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine with aqueous base or, when protecting groups susceptible to reductive cleavage are present, by treatment with a reducing agent selected from the group consisting of hydrogen in the presence of a catalyst and an alkali metal in liquid ammonia, followed by treatment with base; thence, when any of said protecting groups are ketals or acetals, treatment of the resulting O-protected intermediate with aqueous acid.

Claim 29

The process for preparing a 5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine selected from the group consisting of 5-epigentamicin A, 5-epigentamicin B, 5-epigentamicin B 1 , 5-epigentamicin C 1 , 5-epigentamicin C 1a , 5-epigentamicin C 2 , 5-epigentamicin C 2a , 5-epigentamicin C 2b , 5-epigentamicin X 2 , 5-epitobramycin, 5-epiverdamicin, 5-episisomicin, 5-epikanamycin A, 5-epi-3',4'-dideoxykanamycin B, 5-epi-Antibiotic G-52, 5-epi-Antibiotic 66-40B, 5-epi-Antibiotic 66-40D, 5-epi-Antibiotic G-418, 5-epi-Antibiotic JI-20A, 5-epi-Antibiotic JI-20B; and the 1-N-K-derivatives of the foregoing, wherein K is an alkyl substituent selected from the group consisting of alkyl, alkyl cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 8 carbon atoms, the carbon in said alkyl substituent ajacent to the aminoglycoside nitrogen being unsubstituted, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only one of said functions can be attached at any one carbon atom; which comprises the reaction of the corresponding 4,6-di-O-(aminoglycosyl)-2-deoxystreptamine wherein the amino functions and hydroxyl functions other than the 5-hydroxyl function are protected by groups susceptible to reductive cleavage or to basic or mild acid hydrolysis, with an oxidizing agent selected from the group consisting of ruthenium tetroxide, chromic acid in acetone, or chromium trioxide-pyridine complex in methylene chloride; the reaction of the resulting N-protected-O-protected-5-dehydro-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine with an alkali metal borohydride; followed by removal of the protecting groups by treatment of the thereby produced N-protected-O-protected-5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine with aqueous base or, when protecting groups susceptible to reductive cleavage are present, by treatment with a reducing agent selected from the group consisting of hydrogen in the presence of a catalyst and an alkali metal in liquid ammonia, followed by treatment with base; thence, when any of said protecting groups are ketals or acetals, treatment of the resulting O-protected intermediate with aqueous acid.

Claim 30

The process of claim 25 wherein said alkali metal borohydride is lithium tri-secondary butyl borohydride.

Claim 31

A 5-dehydro-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine selected from the group consisting of: 1,3,2',3"-tetra-N-Y-3',2",4"-tri-O-Z-4',6'-O-W-5-dehydrogentamicin A, 1,3-di-N-Y-2',3'-O-W-6',4'; 3", 4"-di-N,O-carbonyl-2"-O-Z-5-dehydrogentamicin B, 1,3-di-N-Y-2',3'-O-W-6',4';3",4"-di-N,O-carbonyl-2"-O-Z-5-dehydrogentamicin B 1 , 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 1 , 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 1a , 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 2 ,

Claim 32

A 5-dehydro-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine selected from the group consisting of: 1,3,2',3"-tetra-N-Y-3',2",4"-tri-O-Z-4',6'-O-W-5-dehydrogentamicin A, 1,3-di-N-Y-2',3'-O-W-6',4'; 3", 4"-di-N,O-carbonyl-2"-O-Z-5-dehydrogentamicin B, 1,3-di-N-Y-2',3'-O-W-6',4';3",4"-di-N,O-carbonyl-2"-O-Z-5-dehydrogentamicin B 1 , 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 1 , 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 1a , 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 2 ,

Claim 33

3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 2a , 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 2b , 1,3,2'-tri-N-Y-3',2"-di-O-Z-4', 6'-O-W-3",4"-N,O-carbonyl-5-dehydrogentamicin X 2 , 1,3,2',6'-3"-penta-N-Y-4',2"-di-O-Z-4",6"-O-W-5-dehydrotobramycin, 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydroverdamicin, 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrosisomicin, 1,3,6',3"-tetra-N-Y-2',2"-di-O-Z-3',4'; 4",6"-di-O-W-5-dehydrokanamycin A, 1,3,6',3"-tetra-N-Y-4',2"-di-O-Z-2',3';4",6"-di-O-W-5-dehydrokanamycin A, 1,3,2',6',3"-penta-N-Y-3',4';4",6"-di-O-W-2"-O-Z-5-dehydrokanamycin B, 1,3,2',6',3"-penta-N-Y-2"-O-Z-4", 6"-O-W-3',4'-dideoxy-5-dehydrokanamicin B, 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydro-Antibiotic G-52, 1,3,2',6',3"-penta-N-Y-2",4"-di-O-Z-5-dehydro-Antibiotic 66-40B, 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydro-Antibiotic 66-40D, 1,3,2'-tri-N-Y-3',2"-di-O-Z-4",6'-O-W-3",4"-N,O-carbonyl-5-dehydro-Antibiotic G-418,

Claim 34

3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 2a , 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrogentamicin C 2b , 1,3,2'-tri-N-Y-3',2"-di-O-Z-4', 6'-O-W-3",4"-N,O-carbonyl-5-dehydrogentamicin X 2 , 1,3,2',6'-3"-penta-N-Y-4',2"-di-O-Z-4",6"-O-W-5-dehydrotobramycin, 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydroverdamicin, 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydrosisomicin, 1,3,6',3"-tetra-N-Y-2',2"-di-O-Z-3',4'; 4",6"-di-O-W-5-dehydrokanamycin A, 1,3,6',3"-tetra-N-Y-4',2"-di-O-Z-2',3';4",6"-di-O-W-5-dehydrokanamycin A, 1,3,2',6',3"-penta-N-Y-3',4';4",6"-di-O-W-2"-O-Z-5-dehydrokanamycin B, 1,3,2',6',3"-penta-N-Y-2"-O-Z-4", 6"-O-W-3',4'-dideoxy-5-dehydrokanamicin B, 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydro-Antibiotic G-52, 1,3,2',6',3"-penta-N-Y-2",4"-di-O-Z-5-dehydro-Antibiotic 66-40B, 1,3,2',6'-tetra-N-Y-2"-O-Z-3",4"-N,O-carbonyl-5-dehydro-Antibiotic 66-40D, 1,3,2'-tri-N-Y-3',2"-di-O-Z-4",6'-O-W-3",4"-N,O-carbonyl-5-dehydro-Antibiotic G-418,

Claim 35

3,2',6'-tetra-N-Y-3',4'-O-W-2"-O-Z-3",4"-N,O-carbonyl-5-dehydro-Antibiotic JI-20A, and 1,3,2',6'-tetra-N-Y-3',4'-O-W-2"-O-Z-3",4"-N,O-carbonyl-5-dehydro-Antibiotic JI-20B, wherein W is a member selected from the group consisting of alkylidene, cycloalkylidene and arylakylidene; Y is a member selected from the group consisting of benzyloxycarbonyl, alkoxybenyzloxycarbonyl, alkoxycarbonyl, and provided said 5-dehydro-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine is devoid of N,O-carbonyl protecting groups, lower alkanoyl; Z is hydrocarboncarbonyl, said hydrocarbon having up to 8 carbon atoms; and the 1-N-K" derivatives of the foregoing wherein K" is an alkyl substituent selected from the group consisting of alkyl, alkyl cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 8 carbon atoms, the carbon in said alkyl substituent adjacent to the aminoglycoside nitrogen being unsubstituted, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only one of said functions can be attached at any one carbon atom; any amino function being substituted by said group, Y, and any hydroxyl being converted to an ester OZ or, when said hydroxyl group is alpha or beta to an amino protecting group Y, the hydroxyl group together with said protecting group Y is converted to an oxazolidinone or a tetrahydro-1,3-oxazin-2-one, respectively, Y and Z being as hereinabove defined.

Claim 36

3,2',6'-tetra-N-Y-3',4'-O-W-2"-O-Z-3",4"-N,O-carbonyl-5-dehydro-Antibiotic JI-20A, and 1,3,2',6'-tetra-N-Y-3',4'-O-W-2"-O-Z-3",4"-N,O-carbonyl-5-dehydro-Antibiotic JI-20B, wherein W is a member selected from the group consisting of alkylidene, cycloalkylidene and arylakylidene; Y is a member selected from the group consisting of benzyloxycarbonyl, alkoxybenyzloxycarbonyl, alkoxycarbonyl, and provided said 5-dehydro-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine is devoid of N,O-carbonyl protecting groups, lower alkanoyl; Z is hydrocarboncarbonyl, said hydrocarbon having up to 8 carbon atoms; and the 1-N-K" derivatives of the foregoing wherein K" is an alkyl substituent selected from the group consisting of alkyl, alkyl cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 8 carbon atoms, the carbon in said alkyl substituent adjacent to the aminoglycoside nitrogen being unsubstituted, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only one of said functions can be attached at any one carbon atom; any amino function being substituted by said group, Y, and any hydroxyl being converted to an ester OZ or, when said hydroxyl group is alpha or beta to an amino protecting group Y, the hydroxyl group together with said protecting group Y is converted to an oxazolidinone or a tetrahydro-1,3-oxazin-2-one, respectively, Y and Z being as hereinabove defined.

Claim 37

A compound of claim 27 wherein Y is benzyloxycarbonyl and Z is benzoyl.

Claim 38

A compound of claim 27 which is 1,3,2',6'-tetra-N-benzyloxycarbonyl-2"-O-benzoyl-3",4"-N,O-carbonyl-5-dehydrogentamicin C 1a .

Claim 41

A pharmaceutical composition comprising an inert carrier and, an antibacterially effective amount of a compound selected from the group consisting of 5-epigentamicin A, 5-epigentamicin B, 5-epigentamicin B 1 , 5-epigentamicin C 1 , 5-epigentamicin C 1a , 5-epigentamicin C 2 , 5-epigentamicin C 2a , 5-epigentamicin C 2b , 5-epigentamicin X 2 , 5-epitobramycin, 5-epiverdamicin, 5-epikanamycin A, 5-epikanamycin B, 5-epi-3',4'-dideoxykanamycin B, 5-epi-Antibiotic G-52, 5-epi-Antibiotic 66-40B, 5-epi-Antibiotic 66-40D, 5-epi-Antibiotic G-418, 5-epi-Antibiotic JI-20A, 5-epi-Antibiotic JI-20B; the 1-N-K-derivatives of the foregoing, wherein K is an alkyl substituent selected from the group consisting of alkyl, alkyl cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 8 carbon atoms, the carbon in said alkyl substituent adjacent to the aminoglycoside nitrogen being unsubstituted, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only of said functions can be attached at any one carbon atom; and the pharmaceutically acceptable acid addition salts thereof.

Claim 42

A pharmaceutical composition comprising an inert carrier and, an antibacterially effective amount of a compound selected from the group consisting of 5-epigentamicin A, 5-epigentamicin B, 5-epigentamicin B 1 , 5-epigentamicin C 1 , 5-epigentamicin C 1a , 5-epigentamicin C 2 , 5-epigentamicin C 2a , 5-epigentamicin C 2b , 5-epigentamicin X 2 , 5-epitobramycin, 5-epiverdamicin, 5-epikanamycin A, 5-epikanamycin B, 5-epi-3',4'-dideoxykanamycin B, 5-epi-Antibiotic G-52, 5-epi-Antibiotic 66-40B, 5-epi-Antibiotic 66-40D, 5-epi-Antibiotic G-418, 5-epi-Antibiotic JI-20A, 5-epi-Antibiotic JI-20B; the 1-N-K-derivatives of the foregoing, wherein K is an alkyl substituent selected from the group consisting of alkyl, alkyl cycloalkyl, alkenyl, aralkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl, and alkylaminohydroxyalkyl, said alkyl substituent having up to 8 carbon atoms, the carbon in said alkyl substituent adjacent to the aminoglycoside nitrogen being unsubstituted, and when said alkyl substituent is substituted by both hydroxyl and amino functions, only of said functions can be attached at any one carbon atom; and the pharmaceutically acceptable acid addition salts thereof.

Claim 43

A compound of claim 19 wherein said 1-N-acyl is 1-N-(S-4-amino-2-hydroxybutyryl).

Claim 44

A compound of claim 19 wherein said 1-N-acyl is 1-N-(S-3-amino-2-hydroxypropionyl).