N-[4-(3-aminopropylamino)butyl]-2,2-dihydroxyacetamide;dihydrochloride

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 10.0 g (45.0 m moles) of 7-guanidinoheptanamide hydrochloride, 13.1 g (45.0 moles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, and 3.2 g (15 m moles) of citric acid in water (100 ml) was evaporated to dryness to give a syrup which contained 1.0 g of water. The resulting syrup was heated at 60° C. for 8 hours. was evaporated to dryness to give a syrup which

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 18 g (80.9 mmoles) of 7-guanidinoheptanamide hydrochloride, 23.6 g (80.9 moles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride obtained in Example 4, and 5.7 g (27 mmoles) of citric acid in water (200 ml) was evaporated to dryness to give a syrup which contained 1.6 g of water. The resulting syrup was heated at 60° C. for 8 hours and purifiled in a procedure similar to that in Example 5 giving 19.0 g (47.3% yield) of white powder of N-[4-(3-aminopropyl)aminobutyl]-2-(7-guanidinoheptanamido)-2-hydroxyethanamide trihydrochloride. was evaporated to dryness to give a syrup which

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 360 mg (1.62 mmoles) of 7-guanidinoheptanamido hydrochloride, 568 mg (1.94 mmoles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride obtained in Example 4, 214 mg (1.62 mmoles) of glutaric acid, and 0.36 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, 5 ml of water was added to to the reaction mixture, then passed through a column (20 mm inner diameter) packed with 150 ml of CM-Sephadex® C-25 (Na-type), and fractionated by the gradient elution with 1.5 liters of water and 1.5 liters of 0.8M aqueous sodium chloride solution. The fractions containing the desired product were combined, then concentrated, and extracted three times with 10 ml of methanol. The methanol layer was passed through a column packed with 150 ml of Sephadex® LH-20, and developed with methanol. The fractions containing the desired product were combined and evaporated to dryness, yielding 317 mg (39% yield) of white powder of N-[4-(3-aminopropyl)aminobutyl]-2-(7-guanidinoheptanamido)-2-hydroxyethanamide trihydrochloride. was added to to the reaction mixture (Na-type), and fractionated by the gradient elution with 1.5 liters of water and 1.5 liters of 0.8M aqueous sodium chloride solution The fractions containing the desired product concentrated extracted three times with 10 ml of methanol The fractions containing the desired product evaporated to dryness

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 360 mg (1.62 mmoles) of 7-guanidinoheptanamido hydrochloride, 568 mg (1.94 mmoles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride obtained in Example 4, 214 mg (1.62 mmoles) of glutaric acid, and 0.36 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, 5 ml of water was added to to the reaction mixture, then passed through a column (20 mm inner diameter) packed with 150 ml of CM-Sephadex® C-25 (Na-type), and fractionated by the gradient elution with 1.5 liters of water and 1.5 liters of 0.8M aqueous sodium chloride solution. The fractions containing the desired product were combined, then concentrated, and extracted three times with 10 ml of methanol. The methanol layer was passed through a column packed with 150 ml of Sephadex® LH-20, and developed with methanol. The fractions containing the desired product were combined and evaporated to dryness, yielding 317 mg (39% yield) of white powder of N-[4-(3-aminopropyl)aminobutyl]-2-(7-guanidinoheptanamido)-2-hydroxyethanamide trihydrochloride. was added to to the reaction mixture (Na-type), and fractionated by the gradient elution with 1.5 liters of water and 1.5 liters of 0.8M aqueous sodium chloride solution The fractions containing the desired product concentrated extracted three times with 10 ml of methanol The fractions containing the desired product evaporated to dryness

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 206.2 mg (0.84 mmole) of 9-guanidino-2-nonenamide hydrochloride, 291.0 mg (1.00 mmole) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, 109.6 mg (0.84 mmole) of glutaric acid and 0.2 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex® C-25 (Na-type) and Sephadex®LH-20 to obtain 135.0 mg (31.1% yield) of a white powder of N-[4-(3-aminopropyl)aminobutyl]-2-(9guanidino-2-nonenamido-2-hydroxyethanamide trihydrochloride. After completion of the reaction the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex®

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 206.2 mg (0.84 mmole) of 9-guanidino-2-nonenamide hydrochloride, 291.0 mg (1.00 mmole) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, 109.6 mg (0.84 mmole) of glutaric acid and 0.2 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex® C-25 (Na-type) and Sephadex®LH-20 to obtain 135.0 mg (31.1% yield) of a white powder of N-[4-(3-aminopropyl)aminobutyl]-2-(9guanidino-2-nonenamido-2-hydroxyethanamide trihydrochloride. After completion of the reaction the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex®

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 202.4 mg (0.86 mmole) of 8-guanidino-2-octenamide hydrochloride, 302.4 mg (1.04 mmoles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, 113.9 mg (0.86 mmole) of glutaric acid and 0.2 ml of water was heated at 60° C. for 24 hours. After completion of the reaction the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex® C-25 (Na-type) and Sephadex® LH-20 to obtain 128.3 mg (29.2% yield) of N-[4-(3-aminopropyl)aminobutyl]-2-(8-guanidino-2-octenamido)-2-hydroxyethanamide trihydrochloride. After completion of the reaction the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex®

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 234.5 mg (1.06 mmoles) of 7-guanidino-2-heptenamide hydrochloride, 372.3 mg (1.27 mmoles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, 140.4 mg (1.06 mmoles) of glutaric acid and 0.2 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex® C-25 (Na-type) and Sephadex® LH-20 to obtain 244.6 mg (46.5% yield) of a white powder of N-[4-(3-aminopropyl)aminobutyl]-2-(7-guanidino-2-heptenamido)-2-hydroxyethanamide trihydrochloride. After completion of the reaction the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex®

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 234.5 mg (1.06 mmoles) of 7-guanidino-2-heptenamide hydrochloride, 372.3 mg (1.27 mmoles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, 140.4 mg (1.06 mmoles) of glutaric acid and 0.2 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex® C-25 (Na-type) and Sephadex® LH-20 to obtain 244.6 mg (46.5% yield) of a white powder of N-[4-(3-aminopropyl)aminobutyl]-2-(7-guanidino-2-heptenamido)-2-hydroxyethanamide trihydrochloride. After completion of the reaction the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex®

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 360 mg (1.62 mmoles) of 7-guanidinoheptanamide hydrochloride, 568 mg (1.94 mmoles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, 214 mg (1.62 mmoles) of glutaric acid and 0.36 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, 5 ml of water was added to the reaction mixture and the resulting mixture was purified in a manner similar to that in Example 1, using CM-Sephadex® C-25 (Na-type) and Sephadex® LH-20 to obtain 317 mg (39% yield) of a white powder of N-[4-(3-aminopropyl)-aminobutyl]-2-(7-guanidinoheptanamido)-2-hydroxyethanamide trihydrochloride. was added to the reaction mixture the resulting mixture was purified in a manner similar to that in Example 1

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 360 mg (1.62 mmoles) of 7-guanidinoheptanamide hydrochloride, 568 mg (1.94 mmoles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, 214 mg (1.62 mmoles) of glutaric acid and 0.36 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, 5 ml of water was added to the reaction mixture and the resulting mixture was purified in a manner similar to that in Example 1, using CM-Sephadex® C-25 (Na-type) and Sephadex® LH-20 to obtain 317 mg (39% yield) of a white powder of N-[4-(3-aminopropyl)-aminobutyl]-2-(7-guanidinoheptanamido)-2-hydroxyethanamide trihydrochloride. was added to the reaction mixture the resulting mixture was purified in a manner similar to that in Example 1

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 446 mg (2.14 mmoles) of 6-guanidinohexanamide hydrochloride, 750 mg (2.57 mmoles) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, 283 mg (2.14 mmoles) of glutaric acid and 0.45 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, 5 ml of water was added to the reaction mixture and the resulting mixture was purified in a manner similar to that in Example 1, using CM-Sephadex® C-25 (Na-type) and Sephadex® LH-20 to obtain 459 mg (44% yield) of a white powder of N-[4-(3-aminopropyl)aminobutyl]-2-(6-guanidinohexanamido)-2-hydroxyethanamide trihydrochloride. was added to the reaction mixture the resulting mixture was purified in a manner similar to that in Example 1