957-68-6 Usage
Synthetic cephalosporins important nucleus
7-aminocephalosporanic acid is abbreviated as 7-ACA, white or almost white crystalline powder, 7-ACA is an important nucleus in synthesis of cephalosporin antibiotics, in the nucleus 7 and 3 chemical transformation can be used to prepare many cephalosporins: cefazolin sodium , cefotaxime sodium, ceftriaxone sodium, cefoperazone sodium, sodium ceftazidime, cefuroxime sodium.
Cephalosporin antibiotics (Cephalosporins) are a cluster of broad-spectrum semisynthetic antibiotics, they all contain the nucleus of 7-aminocephalosporanic acid (7-ACA) , with different groups in the 3 and 7 carbon atoms, forming various cephalosporins with different antibacterial activity and pharmacokinetic characteristics. Cephalosporin antibiotics have broad antibacterial spectrum,strong antibacterial effect, and fewer allergic reactions, and only part of the cross allergic with penicillin and they have varying degrees of stability on the β-lactamase . Cephalosporins have fast development, and many families, they are divided into four generation cephalosporins according to the anti-microbial dynamic "generations" .
They are the same as penicillin, cephalosporins contain β lactam ring , which is necessary to achieve antibacterial efficacy. But penicillins are 6-amino penicillin acid (6-aminopenicillanic acid, 6-APA) derivatives, and cephalosporins nucleus is 7-aminocephalosporanic acid (7-aminocephalosporamic acid, 7-ACA), the latter is from cephalosporin C, it is a fermentation product of Cephalosporium acremonium.
7-aminocephalosporanic acid has a dihydro-thiazine ring (A) and aβ-lactam ring (B), it has a resistant effect on the class of staphylococcus aureus penicillinase. Modifying this nucleus with different side chains can form the entire series of cephalosporin antibiotics. Modifying β-lactam bit 7 (R1), can make antimicrobial efficacy and stability within the β-lactamase change. At 3 bit on-dihydro-thiazine ring substitution (R2), the influence of effect on drug metabolism and pharmacokinetic properties is more staggering than that of antibacterial effect.
Cephamycins are associated with cephalosporin C in chemical structure, the main difference is that they have a 7-α-methoxy group (R3), so that the stability to certain β-lactamase is improved . Cephalosporin is a derivative cephalosporin C which is produced by Streptomyces . Cefotetan is an semi-synthetic derivative of organic mycin G , it is a product of Streptomyces organonensis. Cefmetazole is a semi-synthetic product of 7-aminocephalosporanic acid.
Figure 1 the chemical structure of the 7-aminocephalosporanic acid
β-lactam antibiotics
6-aminopenicillanic acid (6-APA), 7-aminocephalosporanic acid (7-ACA), 3-ammonia Ji Nuoka adriamycin (3-ANA), and 3-amino-acid mono-(3-AMA)are important raw materials of the semi-synthetic β-lactam. In the β-lactam antibiotics mean antibiotics that molecules contain β lactam ring (β-lact-am), including penicillins, cephalosporins, monocyclic beta-lactam antibiotics and the like. Such antibiotics have antibacterial action, the β-lactam portion is similar to D-alanyl-D-alanine terminus of the bacterial cell wall peptidoglycan,they can be combined with endopeptidase activity center, so that the GGT sticky peptidase-catalyzed cross-linking reaction can not be completed, thereby cell wall synthesis is inhibited . As these antibiotics act not only on the cell walls of bacteria, but also interfere with cell wall formation which occurs in the final stages of biosynthesis, so they show unique selectivity on bacteria , there is almost no damage to animal cells which do not have the cell wall ,they are a class of relatively good chemotherapeutic drugs. β-lactam antibiotics are susceptible to β-lactamase destruction which leads to deactivation of them. Some β lactams are β-lactamase (β-lactamase) inhibitors, in combination with the β-lactam antibiotics, the antibiotics can be protected or less destroyed by them , they are important adjuncts to chemotherapy.
The above information is edited by the lookchem of Tian Ye.
Uses
Different sources of media describe the Uses of 957-68-6 differently. You can refer to the following data:
1. Pharmaceutical intermediates. It is the starting material of many semi-synthetic cephalosporin. A variety of semi-synthetic cephalosporin industrial production is through fermentation to obtain cephalosporin C. Then obtain nucleus 7-ACA through chemical cleavage , and then the preparation is fininshed in chemically modified way .
2. It is the starting material for semi-synthetic cephalosporins. Obtained by mild acid hydrolysis of cephalosporin C.
3. Potent inhibitor of bacterial (S. aureus) β-lactamase.
4. 7-Aminocephalosporanic Acid (Cefoperazone EP Impurity E) is the starting material for semi-synthetic cephalosporins. Obtained by mild acid hydrolysis of cephalosporin C.
production method
Starting from the basic raw material of semi-synthetic cephalosporin-cephalosporin C, after esterification with trimethylchlorosilane , and then by phosphorus pentachloride chloride, and Butanol etherifying, and the production is obtained finally through hydrolysis. Yield from cephalosporin C sodium to 7-ACA is about 50%.
Definition
ChEBI: The alpha,beta-unsaturated monocarboxylic acid that is the active nucleus for the synthesis of cephalosporins and intermediates.
General Description
Chemical structure: ?-lactam
Flammability and Explosibility
Notclassified
Check Digit Verification of cas no
The CAS Registry Mumber 957-68-6 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 9,5 and 7 respectively; the second part has 2 digits, 6 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 957-68:
(5*9)+(4*5)+(3*7)+(2*6)+(1*8)=106
106 % 10 = 6
So 957-68-6 is a valid CAS Registry Number.
InChI:InChI=1/C10H12N2O5S/c1-4(13)17-2-5-3-18-9-6(11)8(14)12(9)7(5)10(15)16/h6,9H,2-3,11H2,1H3,(H,15,16)/t6-,9-/m1/s1
957-68-6Relevant articles and documents
Evaluation of different glutaryl acylase mutants to improve the hydolysis of cephalosporin C. in the absence of hydrogen peroxide
Lopez-Gallego, Fernando,Betancor, Lorena,Sio, Charles F.,Reis, Carlos R.,Jimenez, Pol Nadal,Guisan, Jose M.,Quax, Wim J.,Fernandez-Lafuente, Roberto
, p. 343 - 348 (2008)
2-Oxoadipoyl-7-ACA is an intermediate in the conversion of cephalosporin C. (CPC) to 7-aminocephalosporanic acid (7-ACA) when using a new route involving D-amino acid oxidase, catalase and glutaryl acylase. A key point in the reaction design is to avoid the accumulation of hydrogen peroxide in the reaction medium as the yields of 7-ACA decrease in the presence of this compound due to its low stability. Looking for an enzyme with improved activity towards 2-oxoadipoyl-7-ACA, different mutants of glutaryl acylase from Pseudomonas SY-77 with an improved activity towards adipoyl-7-ACA were evaluated. The best results on 2-oxoadipoyl-7-ACA hydrolysis were found with the double mutant Y178F+F375H, which showed a Kcat increase of 6.5-fold and a K m decrease of 3-fold compared to the wild-type (wt) enzyme. When this enzyme was tested in the tri-enzymatic system to convert CPC into 7-ACA, this mutant permitted us to reach more than an 80% yield of 7-ACA using a 3-fold mass excess compared to DAAO; while the wt enzyme gave only a 40% yield. Therefore, the application of this new mutant to the one-pot conversion of CPC to 7-ACA gives very good result in terms of efficiency, yield and rate of the process.
On the substrate preference of glutaryl acylases
Rosini, Elena,Monelli, Claudia Stella,Pollegioni, Loredano,Riva, Sergio,Monti, Daniela
experimental part, p. 52 - 58 (2012/04/11)
The substrate preferences of three acylases - two wild-type enzymes and an evolved variant obtained by directed evolution - which are prototypical enzymes for glutaryl-7-ACA acylase and cephalosporin C acylase subfamilies, have been investigated. A preliminary screening of enzymes' performances on a large set of substrates has been carried out by a colorimetric assay performed in 96-well plates and by a pH-Stat monitoring the hydrolytic activities. Subsequently, kinetic data for selected substrates have been determined, thus elucidating the substrate preference of members of glutaryl-7-ACA acylase vs. cephalosporin C acylase subfamilies. These achievements pave the way to the ability of choosing the best enzyme for the hydrolysis of different compounds of industrial importance.
Influence of substrate structure on PGA-catalyzed acylations. Evaluation of different approaches for the enzymatic synthesis of cefonicid
Terreni, Marco,Tchamkam, Joseph Gapesie,Sarnataro, Umberto,Rocchietti, Silvia,Fernandez-Lafuente, Roberto,Guisan, Jose M.
, p. 121 - 128 (2007/10/03)
The influence of the substrate structure on the catalytic properties of penicillin G acylase (PGA) from Escherichia coli in kinetically controlled acylations has been studied. In particular, the affinity of different β-lactam nuclei towards the active site has been evaluated considering the ratio between the rate of synthesis (vs) and the rate of hydrolysis of the acylating ester (vhl). 7-Aminocephalosporanic acid (7-ACA) and 7-amino-3-(1-sulfomethyl-1,2,3,4-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (7-SACA) showed a good affinity for the active centre of PGA. The enzymatic acylation of these nuclei with R-methyl mandelate has been studied in order to evaluate different approaches for the enzymatic synthesis of cefonicid. The best results have been obtained in the acylation of 7-SACA. Cefonicid (8) was recovered from the reaction mixture as the disodium salt in 65% yield and about 95% of purity. Furthermore, through acylation of 7-ACA, a "one-pot" chemo-enzymatic synthesis was carried out starting from cephalosporin C using three enzymes in sequence: D-amino acid oxidase (DAO), glutaryl acylase (GA) and PGA. Cefonicid disodium salt was obtained in three steps, avoiding any intermediate purification, in 35% overall yield and about 94% purity. This approach presents several advantages compared with the classical chemical processes.
