(2R,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-2-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-3-hydroxycyclohexyl]oxyoxane-3,4-diol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2 g of the ribostamycin trifluoroacetate prepared in the same manner as in Example 1 was taken and dissolved in 35 ml of a liquid mixture of tetrahydrofuran and dimethylformamide (10:1 by volume). This solution was admixed with a solution of 1.74 g of (S)-α-hydroxy-δ-N-phthalimido-n-valeric acid in 16 ml of tetrahydrofuran. A solution of 3.62 g of dicyclohexylcarbodiimide in 16 ml of tetrahydrofuran was added thereto under ice-cooling. The mixture was agitated for 30 minutes under ice-cooling and agitated at ambient temperature for 1 hour 25 minutes to effect the esterification of the hydroxyl groups of the ribostamycin with the substituted valeric acid. The reaction mixture was admixed with 0.8 ml of glacial acetic acid and allowed to stand at ambient temperature overnight to decompose the excess of dicyclohexylcarbodiimide. The dicylcohexylurea by-produced which precipitated was removed by filtration. The filtrate was concentrated to give a solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-δ-N-phthalimido-n-valeryl)-ribostamycins. under ice-cooling cooling agitated at ambient temperature for 1 hour 25 minutes to stand at ambient temperature overnight

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 30 g. of ribostamycin (the free base form) was added to 127 ml. of trifluoroacetic acid under ice-cooling and stirring, and the mixture was allowed to stand at ambient temperature overnight. The resulting solution of amber color was admixed with 400 ml of ethyl ether, and the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration. A 20 g. portion of this ribostamycin trifluoroacetate was taken and then dissolved in 250 ml of tetrahydrofuran together with 16.4 g. of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice. A solution of 36.4 g of dicylcohexylcarbodiimide in 146 ml of tetrahydrofuran was prepared and cooled with ice. Both the solutions was combined together under ice-cooling and stirring. The combined solutions were agitated at ambient temperature for 2-3 hours and admixed with 8 ml of glacial acetic acid to decompose the excess of dicyclohexylcarbodiimide. 3286 mg of dicyclohexylurea produced was deposited and filtered off. The filtrate was concentrated to dryness, giving 43 g of a pale yellow colored solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-γ-N-phthalimido-n-butyryl)-ribostamycins. the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration dissolved in 250 ml of tetrahydrofuran together with 16.4 g of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice cooled with ice cooling stirring The combined solutions were agitated at ambient temperature for 2-3 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 30 g. of ribostamycin (the free base form) was added to 127 ml. of trifluoroacetic acid under ice-cooling and stirring, and the mixture was allowed to stand at ambient temperature overnight. The resulting solution of amber color was admixed with 400 ml of ethyl ether, and the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration. A 20 g. portion of this ribostamycin trifluoroacetate was taken and then dissolved in 250 ml of tetrahydrofuran together with 16.4 g. of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice. A solution of 36.4 g of dicylcohexylcarbodiimide in 146 ml of tetrahydrofuran was prepared and cooled with ice. Both the solutions was combined together under ice-cooling and stirring. The combined solutions were agitated at ambient temperature for 2-3 hours and admixed with 8 ml of glacial acetic acid to decompose the excess of dicyclohexylcarbodiimide. 3286 mg of dicyclohexylurea produced was deposited and filtered off. The filtrate was concentrated to dryness, giving 43 g of a pale yellow colored solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-γ-N-phthalimido-n-butyryl)-ribostamycins. the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration dissolved in 250 ml of tetrahydrofuran together with 16.4 g of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice cooled with ice cooling stirring The combined solutions were agitated at ambient temperature for 2-3 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2 g of the ribostamycin trifluoroacetate prepared in the same manner as in Example 1 was taken and dissolved in 35 ml of a liquid mixture of tetrahydrofuran and dimethylformamide (10:1 by volume). This solution was admixed with a solution of 1.74 g of (S)-α-hydroxy-δ-N-phthalimido-n-valeric acid in 16 ml tetrahydrofuran. A solution of 3.62 g. of dicyclohexylcarbodiimide in 16 ml of tetrahydrofuran was added thereto under ice-cooling. The mixture was agitated for 30 minutes under ice-cooling and agitated at ambient temperature for 1 hour 25 minutes to effect the esterification of the hydroxyl groups of the ribostamycin with the substituted valeric acid. The reaction mixture was admixed with 0.8 ml of glacial acetic acid and allowed to stand at ambient temperature overnight to decompose the excess of dicyclohexylcarbodiimide. The dicylcohexylurea by-produced which precipitated was removed by filtration. The filtrate was concentrated to give a solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-δ-N-phthalimido-n-valeryl)-ribostamycins. under ice-cooling cooling agitated at ambient temperature for 1 hour 25 minutes to stand at ambient temperature overnight

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2 g of the ribostamycin trifluoroacetate prepared in the same manner as in Example 1 was taken and dissolved in 35 ml of a liquid mixture of tetrahydrofuran and dimethylformamide (10:1 by volume). This solution was admixed with a solution of 1.74 g of (S)-α-hydroxy-δ-N-phthalimido-n-valeric acid in 16 ml tetrahydrofuran. A solution of 3.62 g. of dicyclohexylcarbodiimide in 16 ml of tetrahydrofuran was added thereto under ice-cooling. The mixture was agitated for 30 minutes under ice-cooling and agitated at ambient temperature for 1 hour 25 minutes to effect the esterification of the hydroxyl groups of the ribostamycin with the substituted valeric acid. The reaction mixture was admixed with 0.8 ml of glacial acetic acid and allowed to stand at ambient temperature overnight to decompose the excess of dicyclohexylcarbodiimide. The dicylcohexylurea by-produced which precipitated was removed by filtration. The filtrate was concentrated to give a solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-δ-N-phthalimido-n-valeryl)-ribostamycins. under ice-cooling cooling agitated at ambient temperature for 1 hour 25 minutes to stand at ambient temperature overnight

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 30 g. of ribostamycin (the free base form) was added to 127 ml. of trifluoroacetic acid under ice-cooling and stirring, and the mixture was allowed to stand at ambient temperature overnight. The resulting solution of amber color was admixed with 400 ml of ethyl ether, and the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration. A 20 g. portion of this ribostamycin trifluoroacetate was taken and then dissolved in 250 ml of tetrahydrofuran together with 16.4 g. of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice. A solution of 36.4 g of dicylcohexylcarbodiimide in 146 ml of tetrahydrofuran was prepared and cooled with ice. Both the solutions was combined together under ice-cooling and stirring. The combined solutions were agitated at ambient temperature for 2-3 hours and admixed with 8 ml of glacial acetic acid to decompose the excess of dicyclohexylcarbodiimide. 3286 mg of dicyclohexylurea produced was deposited and filtered off. The filtrate was concentrated to dryness, giving 43 g of a pale yellow colored solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-γ-N-phthalimido-n-butyryl)-ribostamycins. the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration dissolved in 250 ml of tetrahydrofuran together with 16.4 g of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice cooled with ice cooling stirring The combined solutions were agitated at ambient temperature for 2-3 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2 g of the ribostamycin trifluoroacetate prepared in the same manner as in Example 1 was taken and dissolved in 35 ml of a liquid mixture of tetrahydrofuran and dimethylformamide (10:1 by volume). This solution was admixed with a solution of 1.74 g of (S)-α-hydroxy-δ-N-phthalimido-n-valeric acid in 16 ml of tetrahydrofuran. A solution of 3.62 g of dicyclohexylcarbodiimide in 16 ml of tetrahydrofuran was added thereto under ice-cooling. The mixture was agitated for 30 minutes under ice-cooling and agitated at ambient temperature for 1 hour 25 minutes to effect the esterification of the hydroxyl groups of the ribostamycin with the substituted valeric acid. The reaction mixture was admixed with 0.8 ml of glacial acetic acid and allowed to stand at ambient temperature overnight to decompose the excess of dicyclohexylcarbodiimide. The dicylcohexylurea by-produced which precipitated was removed by filtration. The filtrate was concentrated to give a solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-δ-N-phthalimido-n-valeryl)-ribostamycins. under ice-cooling cooling agitated at ambient temperature for 1 hour 25 minutes to stand at ambient temperature overnight

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 30 g. of ribostamycin (the free base form) was added to 127 ml. of trifluoroacetic acid under ice-cooling and stirring, and the mixture was allowed to stand at ambient temperature overnight. The resulting solution of amber color was admixed with 400 ml of ethyl ether, and the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration. A 20 g. portion of this ribostamycin trifluoroacetate was taken and then dissolved in 250 ml of tetrahydrofuran together with 16.4 g. of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice. A solution of 36.4 g of dicylcohexylcarbodiimide in 146 ml of tetrahydrofuran was prepared and cooled with ice. Both the solutions was combined together under ice-cooling and stirring. The combined solutions were agitated at ambient temperature for 2-3 hours and admixed with 8 ml of glacial acetic acid to decompose the excess of dicyclohexylcarbodiimide. 3286 mg of dicyclohexylurea produced was deposited and filtered off. The filtrate was concentrated to dryness, giving 43 g of a pale yellow colored solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-γ-N-phthalimido-n-butyryl)-ribostamycins. the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration dissolved in 250 ml of tetrahydrofuran together with 16.4 g of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice cooled with ice cooling stirring The combined solutions were agitated at ambient temperature for 2-3 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2 g of the ribostamycin trifluoroacetate prepared in the same manner as in Example 1 was taken and dissolved in 35 ml of a liquid mixture of tetrahydrofuran and dimethylformamide (10:1 by volume). This solution was admixed with a solution of 1.74 g of (S)-α-hydroxy-δ-N-phthalimido-n-valeric acid in 16 ml tetrahydrofuran. A solution of 3.62 g. of dicyclohexylcarbodiimide in 16 ml of tetrahydrofuran was added thereto under ice-cooling. The mixture was agitated for 30 minutes under ice-cooling and agitated at ambient temperature for 1 hour 25 minutes to effect the esterification of the hydroxyl groups of the ribostamycin with the substituted valeric acid. The reaction mixture was admixed with 0.8 ml of glacial acetic acid and allowed to stand at ambient temperature overnight to decompose the excess of dicyclohexylcarbodiimide. The dicylcohexylurea by-produced which precipitated was removed by filtration. The filtrate was concentrated to give a solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-δ-N-phthalimido-n-valeryl)-ribostamycins. under ice-cooling cooling agitated at ambient temperature for 1 hour 25 minutes to stand at ambient temperature overnight

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 30 g. of ribostamycin (the free base form) was added to 127 ml. of trifluoroacetic acid under ice-cooling and stirring, and the mixture was allowed to stand at ambient temperature overnight. The resulting solution of amber color was admixed with 400 ml of ethyl ether, and the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration. A 20 g. portion of this ribostamycin trifluoroacetate was taken and then dissolved in 250 ml of tetrahydrofuran together with 16.4 g. of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice. A solution of 36.4 g of dicylcohexylcarbodiimide in 146 ml of tetrahydrofuran was prepared and cooled with ice. Both the solutions was combined together under ice-cooling and stirring. The combined solutions were agitated at ambient temperature for 2-3 hours and admixed with 8 ml of glacial acetic acid to decompose the excess of dicyclohexylcarbodiimide. 3286 mg of dicyclohexylurea produced was deposited and filtered off. The filtrate was concentrated to dryness, giving 43 g of a pale yellow colored solid comprising mixed trifluoroacetic acid salts of O-((S)-α-hydroxy-γ-N-phthalimido-n-butyryl)-ribostamycins. the admixture was cooled to precipitate 69 g of a salt of ribostamycin with trifluoroacetic acid which was then removed by filtration dissolved in 250 ml of tetrahydrofuran together with 16.4 g of (S)-α-hydroxy-γ-N-phthalimido-n-butyric acid of the formula ##STR25## The solution was cooled with ice cooled with ice cooling stirring The combined solutions were agitated at ambient temperature for 2-3 hours