Aztreonam E-Isomer

Base Information

• Chemical Name: Aztreonam E-Isomer
• CAS No.: 78110-38-0
• Molecular Formula: C13H17N5O8S2
• Molecular Weight: 435.439
• Hs Code.: 29419000
• European Community (EC) Number: 278-839-9
• NSC Number: 758913
• UNII: 5Q55M3D9UA
• DSSTox Substance ID: DTXSID20244045
• Nikkaji Number: J20.598B,J306.677K
• Wikipedia: Aztreonam
• Wikidata: Q418546
• NCI Thesaurus Code: C28845
• RXCUI: 1272
• ChEMBL ID: CHEMBL410081
• Mol file: 78110-38-0.mol

Synonyms:Az threonam;Az-threonam;Azactam;Azthreonam;Aztreonam;SQ 26,776;SQ-26,776;SQ26,776;Urobactam

Chemical Property of Aztreonam E-Isomer

Chemical Property:

• Appearance/Colour: White crystalline powder
• Melting Point: 227 °C
• Refractive Index: 1.6460 (estimate)
• PKA: pKa -0.7(H2O t=RT Iunde?ned) (Uncertain);2.75(H3O t=RT Iunde?ned) (Uncertain);3.91(H4O t=RT Iunde?ned) (Uncertain)
• PSA: 238.20000
• Density: 1.83 g/cm³
• LogP: 0.81830
• Storage Temp.: Store at 0-5°C
• Solubility.: DMSO (Slightly), Water (Slightly, Heated, Sonicated)
• Water Solubility.: Soluble in DMF/water (1:1) at 50 mg/ml
• XLogP3: 0.3
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 7
• Exact Mass: 435.05185486
• Heavy Atom Count: 28
• Complexity: 808

Purity/Quality:

99%MIN ^*data from raw suppliers

Aztreonam ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 22-24/25-36-26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiinfective Agents
• Canonical SMILES: CC1C(C(=O)N1S(=O)(=O)O)NC(=O)C(=NOC(C)(C)C(=O)O)C2=CSC(=N2)N
• Isomeric SMILES: C[C@H]1[C@@H](C(=O)N1S(=O)(=O)O)NC(=O)/C(=N/OC(C)(C)C(=O)O)/C2=CSC(=N2)N
• Recent ClinicalTrials: Ceftobiprole in the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infections
• Recent EU Clinical Trials: A Phase 3, Multi-Center, Randomized, Single-Blind Study to Assess the Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy in Adults With Complicated Urinary Tract Infection, Acute Uncomplicated Pyelonephritis, Hospital-Acquired Bacterial Pneumonia, Ventilator-Associated Bacterial Pneumonia, and Complicated Intra-Abdominal Infection due to Carbapenem-Resistant Enterobacterales
• indications: It is mainly used for the treatment of infections caused by susceptible strains which include the respiratory system, urinary, reproductive system infections (including acute gonorrhea), intra-abdominal infections, skin and soft tissue infections, before surgery preventing infections, other serious infections, such as sepsis.
• Uses: It is Mainly used for the infections caused by sensitive gram-negative bacteria , including pneumonia, pleurisy, abdominal infections, biliary tract infections, bone and joint infections, skin and soft tissue inflammation, especially for urinary tract infections, but also for sepsis. Because this product has good resistance to enzyme performance, therefore, when a microorganism is not sensitive to penicillins, cephalosporins, aminoglycosides and other drugs ,the product should often be effective. The first totally synthetic monocyclic β-lactam antibiotic. antiserotonin Aztreonam is a synthetic β-lactam antibiotic of the monobactam class. It is effective against Gram-negative bacteria but inactive against Gram-positive bacteria. Its mechanism of action involves the inhibition of mucopeptide synthesis in the bacterial cell wall, thereby blocking peptidoglycan crosslinking. Aztreonam is resistant to hydrolysis by some β-lactamases, but is inactivated by extended-spectrum β-lactamases. The first totally synthetic monocyclic ?lactam antibiotic
• production method: Threonine for raw materials,chloride resulting from the chlorination forms an amide through ammonolysis, protect α-amino with benzyl chloroformate,esterifyβ-hydroxy with methanesulfonyl chloride , the amide group is sulfonated with sulfuric acid tetrabutylammonium , then it is cyclized to generate azetidine derivative in the potassium bicarbonate, then after hydrogen and Deprotection, produce 3-amino-2-methyl-4-oxo-1-sulfo-N oxetane. Afetr dehydration amidation of side chains Azetidine derivative and thiazole derivatives obtained in the above, hydrolyse to deprotect and to obtain aztreonam.
• Description: Aztreonam is the first member of the monobactam class of antibiotics to be introduced into the world market. It possesses high β-lactamase stability and moderately good activity against gram negative aerobes such as E. coli, S. marcescens, -9 Proteus Providencia, Salmonella, g. influenzae, E. gonorrhea, and &. pneumonia. While somewhat less potent against Pseudomonas aeruginosa, it is nonetheless one of the better β-lactams against this species. It has poor activity against gram positive organisms.
• Therapeutic Function: Antibiotic
• Clinical Use: Urinary tract infections, including pyelonephritis and cystitis Lower respiratory tract infections, including pneumonia and bronchitis caused by Gram-negative bacilli Septicemia Skin and skin structure infections, including postoperative wounds, ulcers and burns Intra-abdominal infections, including peritonitis Gynecological infections, including endometritis and pelvic cellulitis
• Drug interactions: Potentially hazardous interactions with other drugs Possibly enhanced anticoagulant effect of coumarins.

Technology Process of Aztreonam E-Isomer

There total 31 articles about Aztreonam E-Isomer which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 86.9%

(3S-trans)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid (80082-65-1) + (Z)-2-<<<1-(2-amino-4-thiazolyl)-2-<(2-benzothiazolyl)thio>-2-oxoethylidene>amino>oxy>-2-methyl propanoic acid 1,1-dimethylethyl ester (89604-92-2,158183-05-2) → azthreonam (78110-38-0,80951-91-3,149496-40-2,99341-02-3,85506-30-5)

Guidance literature:

(3S-trans)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid; (Z)-2-<<<1-(2-amino-4-thiazolyl)-2-<(2-benzothiazolyl)thio>-2-oxoethylidene>amino>oxy>-2-methyl propanoic acid 1,1-dimethylethyl ester; With pyridine; In acetonitrile; at -5 ℃; for 4h;

With nitric acid; at 35 ℃; for 2h; pH=1; Solvent; Reagent/catalyst; Temperature;

Reference yield: 81.0%

(Z)-2-[[[1-(2-amino-4-thiazolyl)-2-(3-oxido-1H-benzotriazol-1-yl)-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid methanesulfonate (1:1) salt (139714-28-6) + (3S-trans)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid (80082-65-1) → azthreonam (78110-38-0,80951-91-3,149496-40-2,99341-02-3,85506-30-5)

Guidance literature:

(Z)-2-[[[1-(2-amino-4-thiazolyl)-2-(3-oxido-1H-benzotriazol-1-yl)-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid methanesulfonate (1:1) salt; (3S-trans)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid; With triethylamine; In ethanol; water; at -6 - -3 ℃; for 3h;

With hydrogenchloride; In ethanol; water; at -3 - 0 ℃;

DOI:10.1021/op025572d

Reference yield: 72.0%

[3S-[3α(Z),4β]]-3-[[(2-amino-4-thiazolyl)[(1-t-butoxycarbonyl-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid (330944-50-8) → azthreonam (78110-38-0,80951-91-3,149496-40-2,99341-02-3,85506-30-5)

Guidance literature:

With hydrogenchloride; water; at 0 - 65 ℃; for 4.75h;

upstream raw materials:

3-<<(2-amino-4-thiazolyl)-<<1-(diphenylmethoxycarbonyl)-1-methyl ethoxy>-imino>-acetyl>-amino>-4-methyl-2-oxoazetidi-ne-1-sulfonic acid

[3S-[3α(Z),4β]]-3-[[(2-amino-4-thiazolyl)[(1-t-butoxycarbonyl-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid

aztreonam

water

Downstream raw materials:

aztreonam

Refernces

Practical synthetic approaches to intermediates for the preparations of the novel O-sulfonated-N-hydroxy-2-azetidinone antibiotics

10.1016/S0040-4020(01)92150-7

The research focuses on the practical synthesis of intermediates for the preparation of novel 0-sulfonated-N-hydroxy-2-azetidinone antibiotics, which are a class of monocyclic β-lactam antibiotics. The purpose of the study was to develop a simplified and commercially viable synthetic approach to key intermediates for the preparation of these antibiotics, including nocardicins, monobactams, and the new 0-sulfonated N-hydroxy-2-azetidinone antibiotics. The researchers achieved this by hydroxaminolysis of N-protected serine esters to produce hydroxamic acids, followed by acylation and cyclization to yield β-lactams. The process also involved solvolytic deacylation to obtain the parent N-hydroxy-2-azetidinones, which could be further converted to N-unsubstituted 2-azetidinones or the novel 0-sulfonated antibiotics. The chemicals used in the process included N-protected serine esters, hydroxylamine, acyl groups, and various reagents for cyclization and purification steps, such as pyridine-SO3 for the final step to produce the 0-sulfonated N-hydroxy-2-azetidinones. The conclusions of the research indicated that the developed synthetic approach was practical, did not require expensive reagents, and minimized the use of chromatography, making it a potentially commercially viable method for producing these antibiotics.