32385-11-8

Basic information

• Product Name: Sisomicin
• Synonyms: O-3-deoxy-4C-methyl-3-(methylamino)--L-arabinopiranozyl-(1-6)-O[2,6-diamino-2,3,4,6-tetradeooxy-a-D-glycerohexy-4-enopiranozyl-(1-4)]-2-deoxy-D-streptamycin;O-3-Deoxy-4-C-methyl-3-(methylamino)--L-arabinopyranosyl-(1-6)-O-[2,6-diamino-2,3,4,6-tetradeoxy-a-D-glycero-hex-4-enopyranosyl-(1-4)]-2-deoxy- D-Streptamine;6-O-(4-C-Methyl-3-methylamino-3-deoxy-β-L-arabinopyranosyl)-4-O-(2,6-diamino-2,3,4,6-tetradeoxy-α-D-glycero-4-hexenopyranosyl)-2-deoxy-D-streptamine;Sisomicin;Sisomicin (C1a oxidation peak);O-3-Deoxy-4-C-Methyl-3-(MethylaMino)-β-L-arabinopyranosyl-(1-6)-O-[2,6-diaMino-2,3,4,6-tetradeoxy-α-D-glycero-hex-4-enopyranosyl-(1-4)]-2-deoxy- D-StreptaMine;Antibiotic 6640;Dehydrogentamicin Cla
• CAS NO: 32385-11-8
• Molecular Formula: C₁₉H₃₇N₅O₇
• Molecular Weight: 545.607
• EINECS: 251-018-2
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 32385-11-8.mol
• Article Data: 9

Chemical Properties

• Melting Point: 80-93°C
• Boiling Point: 556.56°C (rough estimate)
• Flash Point: 362.982 °C
• Appearance: /
• Density: 1.2777 (rough estimate)
• Vapor Pressure: 1.79E-30mmHg at 25°C
• Refractive Index: 1.7600 (estimate)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under Inert Atmosphere
• Solubility: Aqueous Acid (Slightly), DMSO (Slightly), Methanol (Slightly), Water (Slightly,
• PKA: 13.29±0.70(Predicted)
• CAS DataBase Reference: Sisomicin(CAS DataBase Reference)
• NIST Chemistry Reference: Sisomicin(32385-11-8)
• EPA Substance Registry System: Sisomicin(32385-11-8)

Safety Data

• Hazardous Substances Data: 32385-11-8(Hazardous Substances Data)

Usage

Description

Sisomicin, also known as Siseptin, is a gentamicin-like aminoglycoside antibiotic produced by Micromonospora inyoensis. It exhibits a broad-spectrum antibiotic activity and is very similar to gentamicin in its antimicrobial spectrum and other properties. Sisomicin is an off-white solid and has been commercially available in Europe as a sulfate under the brand name Siseptin (Schering).

Uses

Used in Pharmaceutical Industry:
Sisomicin is used as an antibacterial agent for its broad-spectrum antibiotic activity. It is particularly effective against Enterobacteriaceae and shows higher activity against Pseudomonas aeruginosa compared to gentamicin, although not as active as tobramycin. The drug is used to treat various infections, such as urinary tract infections and Gram-negative bacillary septicemias.
Used in Medical Treatments:
Sisomicin is used as a therapeutic agent for combating bacterial infections caused by susceptible organisms. It binds to ribosomes, inhibiting protein synthesis and leading to the death of bacteria. However, there is almost complete cross-resistance between gentamicin and sisomicin with most Gram-negative bacilli due to the action of plasmid-coded modifying enzymes.
Despite its similarities to gentamicin, sisomicin does not offer significant advantages over gentamicin and has had limited clinical trials. Its dosage, administration methods, and pharmacokinetics are similar to those of gentamicin, and the toxicity of the two drugs is also likely to be about the same.

Originator

Pathomyci n,Byk-Essex,W. Germany,1976

Manufacturing Process

Tank fermentation of Micromonospora inyoensis - Germination stage 1: Under aseptic conditions, add a lyophilized culture (or cells obtained from a slant culture) of M. inyoensis to a 300 ml shake flask containing 100 ml of the following sterile medium: Beef extract 3 g Tryptone 5 g Yeast extract 5 g Dextrose 1 g Starch 24 g Calcium carbonate 2 g Tap water 1,000 ml Incubate the flask and its contents for 5 days at 35°C on a rotary shaker (280 rpm, 2'' stroke).Germination stage 2: Aseptically transfer 25 ml of the fermentation medium of Germination stage 1 to a 2-l shake flask containing 500 ml of the above described sterile germination medium. Incubate the flask and its contents for 3 days at 28{]C on a rotary shaker (280 rpm, 2'' stroke).Fermentation stage: Aseptically transfer 500 ml of the medium obtained from Germination stage 2 to a 14-l fermentation tank containing 9.5 l of the following sterile medium: Dextrin 50 g Dextrose 5 g Soybean meal 35 g Calcium carbonate 7 g Cobalt chloride 10-6M Tap water 1,000 ml Antifoam (GE 60) 10 ml Prior to sterilizing the above described medium, adjust the pH to 8. Aerobically ferment for 66 to 90 hours while stirring at 250 rpm with air input at 4.5 l/l/min and 25 psi. The potency of the antibiotic produced at the end of this period reaches a peak of 150 to 225 mcm/ml and remains relatively constant. The pH of the fermentation medium changes slightly during the antibiotic production, varying in the range of 6.8 to 7.3.Isolation of Antibiotic 66-40 - The whole broth is adjusted to pH 2 with 6N sulfuric acid. (For the purpose of this example, quantities are given in terms of 170 l of fermentation broth obtained by pooling acidified broth from 17 batches.) The acidified broth is stirred for about 15 minutes and then filtered. Wash the mycelium with water and combine the washings with the filtrate. Adjust the pH of the filtrate to 7 with 6N ammonium hydroxide.To the neutralized filtrate, add sufficient oxalic acid to precipitate calcium and filter. Reneutralize the filtrate with ammonium hydroxide. Charge the filtrate onto a cationic exchange adsorption column containing 1,500 to 2,000 g of IRC-50 Amberlite in its ammonium form. Discard the eluate, wash the resin with water, and elute with 2N ammonium hydroxide. Collect 400 ml fractions and monitor by disc testing with S. aureus ATCC-6538P. Combine active fractions and evaporate to dryness under vacuum obtaining about 28 g of crude Antibiotic 6640 having an activity of about 500 mcm/g.Purification of Antibiotic 66-40 - Dissolve 28 g of crude Antibiotic 6640 in 100 ml of distilled water and charge to an anion exchange adsorption column (Dowex 1 x 2) in the hydroxyl form. Slurry 2,000 g of the resin in water into a column 2,5" in diameter and 36" high. Elute the column with distilled water at a rate of about 23 ml/min collecting 100 ml fractions and monitor with a conductivity meter and by disc testing against Staphylococcus aureus.The disc testing provides a gross separation of antibiotic-containing eluate fractions from those devoid of antibiotic. To insure that the fractions are properly combined, a portion of each fraction is paper chromatographed using the lower phase of a chloroform:methanol:17% ammonium hydroxide system (2:1:1). Each paper is sprayed with ninhydrin and the eluates containing like material are combined and lyophilized yielding about 5.7 g of Antibiotic 66-40 assaying about 900 mcm/mg.

Therapeutic Function

Antibiotic

Antimicrobial activity

A fermentation product of Micromonospora inyoensis. A dehydro derivative of gentamicin C1a, supplied as the sulfate salt. It is virtually identical to gentamicin in activity and pharmacokinetic behavior. An intramuscular dose of 1–1.5 mg/kg achieves a peak plasma concentration of 1.5–9.0 mg/L after 0.5–1 h. It is widely distributed in body water, but concentrations in CSF are low, even in the presence of inflammation. The plasma half-life is 2.5 h and protein binding is <10%. It is eliminated almost completely over 24 h in the glomerular filtrate. Excretion decreases proportionately with renal impairment and because of the virtual identity of the behavior of the two compounds, a gentamicin nomogram can be used to adjust dosage. About 40% of the dose is eliminated during a 6-h dialysis period, during which the elimination half-life falls to about 8 h. Mild and reversible impairment of renal function occurs in about 5% of patients. Nephrotoxicity is more likely to be seen in those with pre-existing renal disease or treated concurrently with other potentially nephrotoxic drugs. Ototoxicity mainly affecting vestibular function has been found in about 1% of patients. Neuromuscular blockade and other effects common to aminoglycosides including rashes, paresthesiae, eosinophilia and abnormal liver function tests have been described. Its uses are identical to those of gentamicin, which it closely resembles. It is of limited availability.

InChI:InChI=1/C19H37N5O7.H2O4S/c1-19(27)7-28-18(13(26)16(19)24-2)31-15-11(23)5-10(22)14(12(15)25)30-17-9(21)4-3-8(6-20)29-17;1-5(2,3)4/h3,9-18,24-27H,4-7,20-23H2,1-2H3;(H2,1,2,3,4)/t9-,10+,11-,12+,13?,14-,15+,16-,17-,18-,19+;/m1./s1

Upstream product

• 53179-09-2 Sisomicin sulfate 
• 66065-86-9 3,2',6'-tri-N-acetylsisomicin 
• 66065-86-9 N-[(1S,2R,3R,4S)-2-[(2S,3R)-3-Acetylamino-6-(acetylamino-methyl)-3,4-dihydro-2H-pyran-2-yloxy]-5-amino-4-((2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-methylamino-tetrahydro-pyran-2-yloxy)-3-hydroxy-cyclohexyl]-acetamide 
• 66567-31-5 N-[(1S,2R,3S,4S)-2-[(2S,3R)-3-Acetylamino-6-(acetylamino-methyl)-3,4-dihydro-2H-pyran-2-yloxy]-4-((2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-methylamino-tetrahydro-pyran-2-yloxy)-5-ethylamino-3-hydroxy-cyclohexyl]-acetamide 
• 66065-91-6 3,2',6'-tri-N-acetyl-1-deamino-1-oxosisomicin 

Downstream Products

• 60577-52-8 C₆₀H₇₁N₅O₁₈ 
• 69992-04-7 1,3,2',6'-Tetrakis-N-(benzyloxycarbonyl)sisamin 
• 1154758-32-3 6'-trifluoroacetyl-2',3-diPNZ-sisomicin 
• 1154758-54-9 4-nitrobenzyl (((2S,3R)-3-amino-2-(((1R,2S,3S,4R,6S)-4,6-diamino-3-(((2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)tetrahydro-2H-pyran-2-yl)oxy)-2-hydroxycyclohexyl)oxy)-3,4-dihydro-2H-pyran-6-yl)methyl)carbamate 
• 1154758-64-1 6',2'-diPNZ-sisomicin 
• 1154758-63-0 tert-butyl ((2R,3R,4R,5R)-2-(((1S,2S,3R,4S,6R)-3-(((2S,3R)-6-(aminomethyl)-3-((tert-butoxycarbonyl)amino)-3,4-dihydro-2H-pyran-2-yl)oxy)-4-((tert-butoxycarbonyl)amino)-6-((S)-4-((tert-butoxycarbonyl)amino)-2-hydroxybutanamido)-2-hydroxycyclohexyl)oxy)-3,5-dihydroxy-5-methyltetrahydro-2H-pyran-4-yl)(methyl)carbamate 
• 1154758-74-3 6'-tert-butyldimethylsiloxyethyl-2',3,3-tri-(tert-butoxycarbonyl)-1-[N-tert-butoxycarbonyl-4-amino-2(S )-hydroxybutyryl]sisomicin 
• 1154757-24-0 ACHN-490 
• 1225277-47-3 1,3,2',6'-tetraazido-sisomicin 
• 1154758-55-0 4-nitrobenzyl (((2S,3R)-2-(((1R,2R,3S,4R,6S)-4-amino-6-((tert-butoxycarbonyl)amino)-3-(((2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)tetrahydro-2H-pyran-2-yl)oxy)-2-hydroxycyclohexyl)oxy)-3-((tert-butoxycarbonyl)amino)-3,4-dihydro-2H-pyran-6-yl)methyl)carbamate 

Relevant articles and documents

Synthesis method of plazomicin or salt of plazomicin

The invention relates to a synthesis method of plazomicin or salt of the plazomicin. Specifically, the synthesis method uses a compound 6 as a raw material, six steps of exchange reaction, amino protection reaction, PNZ protecting group removal reaction, reductive amination reaction, degradation reaction and amino-protecting group removal reaction are sequentially performed, and finally the plazomicin or the salt of the plazomicin is prepared. The details of specific steps are described in the description. The synthesis method has the advantages of being few in steps, high in reaction selectivity, simple in operation, low in material cost and the like, and is very suitable for industrial application.

TREATMENT OF URINARY TRACT INFECTIONS WITH ANTIBACTERIAL AMINOGLYCOSIDE COMPOUNDS

A method for treating a urinary tract infection in a mammal in need thereof is disclosed, the method comprising administering to the mammal an effective amount of an antibacterial aminoglycoside compound.

Process for the preparation of purified aminoglycoside antibiotics

The invention relates to an improved process for the isolation and purification of aminoglycoside antibiotics of Formula (I) as defined herein combining selective lipophilization of the compound of Formula (I) in the crude product obtained by fermentation with controlled liquid/liquid extraction.