Sulbactam

Sulbactam(Betamaze) is an irreversible β-lactamase inhibitor.Target: β-lactamase; AntibacterialSulbactam is a mechanism-based inhibitor of beta-lactamase enzymes used in clinical practice. sulbactam was the antimicrobial agent responsible for the killing of these organisms [1]. sulbactam may prove effective for non-life-threatening A. baumannii infections. Its role in the treatment of severe infections is unknown. However, the current formulation of sulbactam alone may allow its use at h

Sulbactam is a member of penicillanic acids.|Sulbactam is a β-lactamase inhibitor given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys antibiotic activity.|Sulbactam is a beta Lactamase Inhibitor. The mechanism of action of sulbactam is as a beta Lactamase Inhibitor.|Sulbactam is a semi-synthetic beta-lactamase inhibitor. The beta-lactam ring of sulbactam irreversibly binds to beta-lactamase at or near its active site, thereby blocking enzyme activity and preventing metabolism of other beta-lactam antibiotics by the enzyme. Combining this agent with a beta-lactamase susceptible antibiotic, such as penicillins or a cephalosporin, to treat infections caused by beta-lactamase producing organisms, results in a decreased turnover rate of the beta-lactamase sensitive antibiotic and enhances its antibacterial activity.|A beta-lactamase inhibitor with very weak antibacterial action. The compound prevents antibiotic destruction of beta-lactam antibiotics by inhibiting beta-lactamases, thus extending their spectrum activity. Combinations of sulbactam with beta-lactam antibiotics have been used successfully for the therapy of infections caused by organisms resistant to the antibiotic alone.

Method 1: 6.51g (41mmo1) potassium permanganate is dissolved in 130ml water and 4.95ml glacial acetic acid, and cooled to about 5°C. A solution of 4.58 g (21 mmol) of sodium penicillin dissolved in 50rnl of water at about 5°C was added, and stirred at 5°C for 20 min. Remove the cold bath, add solid sodium bisulfite until the color of potassium permanganate disappears, and then filter. To the filtrate was added half of its volume of saturated sodium chloride aqueous solution to adjust the pH to 1.7. The acidic aqueous solution was extracted with ethyl acetate. The extract was dried and concentrated under reduced pressure to obtain 3.47 g of sulbactam. The acidic aqueous solution after extraction was saturated with sodium chloride and extracted with ethyl acetate. The extract was dried and concentrated to obtain 0.28 g of sulbactam. A total of 3.75g sulbactam was obtained with a yield of 78%. Method 2: Use 6-APA as raw material. Mix sodium bromide and sulfuric acid (hydrobromic acid can also be used), add 67APA at 0°C with stirring. After 6-APA is completely dissolved, add an aqueous solution of sodium nitrite dropwise. After the completion of the reaction, the reaction is below 4°C. The aqueous layer was separated and extracted twice with dichloromethane. The extract was used to extract oil again, and then washed with water. Add equal amount of water to neutralize to neutral. The aqueous solution containing 6-bromopenicillanic acid was separated and used directly in the next reaction. Potassium permanganate, water and glacial acetic acid are mixed, and the aqueous solution of 6-bromopenicillanic acid obtained in the previous reaction is added under stirring at 0°C. React below 5°C for 1h. Add sodium bisulfite to decolorize, then add chloroform, adjust to pH=2 with sulfuric acid. The chloroform layer was separated, and the aqueous layer was extracted with chloroform. The chloroform layers were combined, washed with water and dried. Chloroform was distilled off under reduced pressure, that is, crystals were precipitated, collected by filtration, washed with chloroform, and dried to obtain 6-bromopenicillane sulfonic acid. 6-Bromopenicillin sulfone acid is mixed with water, adjusted to neutrality with sodium hydroxide, 10% palladium-carbon and disodium hydrogen phosphate are added for hydrogenolysis. Filter, add ethyl acetate to the filtrate, and adjust to pH=2 with sulfuric acid. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water, dried and concentrated under reduced pressure to obtain yellowish crystals, which were washed with ethyl acetate and dried in vacuo to obtain sulbactam, which can be recrystallized from ethyl acetate-petroleum ether. Method 3: Add bromine, sulfuric acid and sodium nitrite to methylene chloride at 5°C. Then add 6-APA in batches at 4 to 10°C. After stirring at 5°C, sodium bisulfite solution was added dropwise at 5~15°C until the bromine color disappeared, forming a pale yellow solution. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The organic layers were combined and washed with brine to obtain a dibromide in dichloromethane, which was used directly in the next reaction. Water was added to the dichloromethane solution of the above dibromide, and sodium hydroxide solution was added dropwise until Ph=7.0. Separate the water layer and extract the organic layer with water. The extract and the water layer were combined, and potassium permanganate solution was added dropwise to the water layer at -5°C with stirring. Add ethyl acetate and adjust to pH=1.23 with hydrochloric acid. Below 10°C, the sodium bisulfite solution was added dropwise to the formed two-phase solution, and the pH value was maintained at 1.25 to 1.35 with hydrochloric acid. The aqueous layer was saturated with sodium chloride and separated, and extracted with ethyl acetate. After the extract and the organic layer were combined, washed with brine, dried, and filtered to obtain an ethyl acetate solution containing the oxidation product, which was directly used in the next reaction. The above ethyl acetate solution, saturated sodium bicarbonate solution and 5% palladium-carbon were hydrogenated under a hydrogen pressure of about 0.35 MPa. Filter, cool to about 5°C, and adjust pH to 1.2 with hydrochloric acid. After the aqueous layer was saturated with sodium chloride, it was extracted with ethyl acetate. The extract and the organic layer were combined, dried, and concentrated under reduced pressure to obtain crude sulbactam in 57.5% yield. Method 4: Take penicillin G as raw material, oxidize m-chloroperoxybenzoic acid to sulfone, and then hydrolyze to obtain sulbactam.

A β-lactamase inhibitor.

Molecular Weight:233.24
XLogP3:-1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:233.03579362
Monoisotopic Mass:233.03579362
Topological Polar Surface Area:100
Heavy Atom Count:15
Complexity:446
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes