Amikacin Disulfate CAS 39831-55-5
Introduction：Basic information about Amikacin Disulfate CAS 39831-55-5, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Amikacin Disulfate Basic information
| Product Name: | Amikacin Disulfate |
| Synonyms: | AMIKACIN DISULFATE;AMIKACIN DISULFATE SALT;AMIKACIN SULFATE;(s)-ysulfate(1:2)(salt);antibioticbb-k8sulfate;α-d-glucopyranosyl-(1-4))-n(sup 1)-(4-amino-2-hydroxy-1-oxobutyl)-2-deoxy;Amikacin disulphate salt;1-N-[L-(-)-γ-AMino-α-hydroxybutyryl]kanaMycin A Sulfate |
| CAS: | 39831-55-5 |
| MF: | C22H45N5O17S |
| MW: | 683.68 |
| EINECS: | 254-648-6 |
| Product Categories: | Inhibitors;Antibiotics;AMIKIN;Amines;Intermediates & Fine Chemicals;Oligosaccharides;Pharmaceuticals;Active Pharmaceutical Ingredients |
| Mol File: | 39831-55-5.mol |
Amikacin Disulfate Chemical Properties
| Melting point | 220-230 C |
| alpha | D22 +74.75° (water) |
| storage temp. | Inert atmosphere,2-8°C |
| solubility | H2O: 50 mg/mL, clear, colorless |
| form | powder |
| color | white to off-white |
| PH | pH(10g/L, 25℃) : 2.0～4.0 |
| Water Solubility | Soluble in water at 50mg/ml with warming |
| Merck | 13,404 |
| BRN | 6172633 |
| Stability: | Hygroscopic |
| Major Application | pharmaceutical (small molecule) |
| InChIKey | HIBICIOPDUTNRR-ZCBGRSKCNA-N |
| CAS DataBase Reference | 39831-55-5(CAS DataBase Reference) |
| EPA Substance Registry System | Amikacin sulfate (39831-55-5) |
Safety Information
| Hazard Codes | Xi |
| Risk Statements | 36/37/38 |
| Safety Statements | 26-36 |
| WGK Germany | 2 |
| RTECS | WK1961200 |
| F | 3-10 |
| HS Code | 29419000 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Repr. 2 Skin Sens. 1 |
| Toxicity | LD50 oral in rabbit: > 3gm/kg |
| Chemical Properties | White Solid |
| Originator | Amikin,Bristol,US,1976 |
| Uses | Semisynthetic aminoglycoside antibiotic derived from Kanamycin A. Antibacterial. |
| Uses | Analgesic |
| Uses | Amikacin disulfate is used as an aminoglycoside antibiotic derived from Kanamycin A, used for treating infections with multidrug resistant Gram negative bacteria such as Pseudomonas aeruginosa, Acinetobacter, and Enterobacter. It is commonly used in the treatment of drug-resistant mycobacteria. It is used to study organism-directed delivery of antibiotics as well as drug resistance. |
| Definition | ChEBI: An aminoglycoside sulfate salt obtained by combining amikacin with two molar equivalents of sulfuric acid. |
| Manufacturing Process | Preparation of L-(-)-γ-benzyloxycarbonylamino-α-hydroxybutyric acid: L-(-)-γ-amino-α-hydroxybutyric acid (7.4 g, 0.062 mol) was added to a solution of5.2 grams (0.13 mol) of sodium hydroxide in 50 ml of water. To the stirredsolution was added dropwise at 0-5°C over a period of 0.5 hour, 11.7 grams(0.068 mol) of carbobenzoxy chloride and the mixture was stirred for anotherhour at the same temperature. The reaction mixture was washed with 50 mlof ether, adjusted to pH 2 with dilute hydrochloric acid and extracted with four80 ml portions of ether. The ethereal extracts were combined, washed with asmall amount of saturated sodium chloride solution, dried with anhydroussodium sulfate and filtered. The filtrate was evaporated in vacuum and theresulting residue was crystallized from benzene to give 11.6 grams (74%) ofcolorless plates; MP 78.5°C to 79.5°C. Preparation of N-Hydroxysuccinimide Ester of L-(-)-γ-Benzyloxycarbonylamino-α-hydroxybutyric acid: A solution of 10.6 grams (0.042 mol) of L-(-)-γ-benzyloxycarbonylamino-α-hydroxybutyric acid and 4.8 grams (0.042 mol) ofN-hydroxysuccinimide in 200 ml of ethyl acetate was cooled to 0°C and then8.6 grams (0.042 mol) of dicyclohexylcarbodiimide was added. The mixturewas kept overnight in a refrigerator. The dicyclohexylurea which separatedwas filtered off and the filtrate was concentrated to about 50 ml underreduced pressure to give colorless crystals of L-(-)-γ-benzyloxycarbonylamino-α-hydroxybutyric acid which were collected by filtration; 6.4 grams, MP 121-122.5°C. The filtrate was evaporated to dryness in vacuum and the crystallineresidue was washed with 20 ml of a benzene-n-hexane mixture to give anadditional amount of L-(-)-γ-benzyloxycarbonylamino-α-hydroxybutyric acid.The total yield was 13.4 grams (92%). Preparation of 1-[L-(-)-γ-Benzyloxycarbonylamino-α-Hydroxybutyryl]-6'-Carbobenzoxykanamycin A: A solution of 1.6 grams (4.6 mmol) of L-(-)-γ-benzyloxycarbonylamino-α-hydroxybutyric acid in 40 ml of ethylene glycoldimethyl ether (DME) was added dropwise to a stirred solution of 2.6 grams(4.2 mmol) of 6'-monobenzyloxycarbonylkanamycin A in 40 ml of 50%aqueous ethylene glycol dimethyl ether and the mixture was stirred overnight.The reaction mixture was evaporated under reduced pressure to give a brownresidue 1-[L-(-)-γ-benzyloxycarbonylarnino-α-hydroxybutyryl]-6'-carbobenzoxykanamycin A which was used for the next reaction withoutfurther purification. Preparation of 1-[L-(-)-γ-Amino-α-Hydroxybutyryl] Kanamycin A: The crudeproduct 1-[L-(-)-γ-benzyloxycarbonylamino-α-hydroxybutyryl]-6'-carbobenzoxykanamycin A was dissolved in 40 ml of 50% aqueous dioxaneand a small amount of insoluble material was removed by filtration. To thefiltrate was added 0.8 ml of glacial acetic acid and 1 gram of 10% palladiumon-charcoal and the mixture was hydrogenated at room temperature for 24hours in a Parr hydrogenation apparatus. The reaction mixture was filtered toremove the palladium catalyst and the filtrate was evaporated to dryness invacuum. The residue was dissolved in 30 ml of water and chromatographed on a column of CG-50 ion exchange resin (NH4+ type, 50 cm x 1.8 cm). Thecolumn was washed with 200 ml of water and then eluted with 800 ml of 0.1N NH4OH, 500 ml of 0.2 N NH4OH and finally 500 ml of 0.5 N NH4OH. Tenmilliliter fractions were collected and fractions 146 to 154 contained 552 mg(22%. based on carbobenzoxykanamycin A, 6'-monobenzyloxycarbonylkanamycin A) of the product which was designatedBB-K8 lot 2. MP 187°C (dec). Relative potency against B. subtilis (agar plate)= 560 mcg/mg (standard: kanamycin A free base). A solution of 250 mg of BB-K8 lot 2 in 10 ml of water was subjected tochromatography on a column of CG-50 (NH4+ type, 30 cm x 0.9 cm). Thecolumn was washed with 50 ml of water and then eluted with 0.2 N NH4OH.Ten milliliter fractions were collected. Fractions 50 to 63 were combined andevaporated to dryness under reduced pressure to give 98 mg of the pureproduct base. Preparation of the Monosulfate Salt of 1-[L-(-)-γ-Amino-α-Hydroxybutyryl]Kanamycin A: One mol of 1-[L-(-)-γ-amino-α-hydroxybutyryl] kanamycin A isdissolved in 1 to 3 liters of water. The solution is filtered to remove anyundissolved solids. To the chilled and stirred solution is added one mol ofsulfuric acid dissolved in 500 ml of water. The mixture is allowed to stir for 30minutes, following which cold ethanol is added to the mixture till precipitationoccurs. The solids are collected by filtration and are determined to be thedesired monosulfate salt. |
| Brand name | Amikin (Apothecon). |
| Therapeutic Function | Antibacterial |
| Safety Profile | Poison by intravenous route.Moderately toxic by intraperitoneal and subcutaneousroutes. An experimental teratogen. Other experimentalreproductive effects. When heated to decomposition itemits very toxic fumes of NOx and SOx. |
Amikacin Disulfate Preparation Products And Raw materials
| Raw materials | Sulfuric acid-->Acetone-->Sodium hydroxide-->Hydrogen-->Palladium hydroxide-->Benzyl chloroformate-->N-Hydroxysuccinimide-->AMIKACIN |
