6-Aminopenicillinic acid

In some cases particular processes are espeeially important because of the value of the products produced and also the amounts of enzyme used, i.e. from both the enzyme producer and user standpoints. Therefore the examples on fructose syrups and 6-aminopenicillinic acid have been expanded to include much information on the business and technical strategies employed, and detailed proeess economic aspects respectively. Many other examples of biocatalysis-based commercial processes and products also exist with many others undergoing development. These other products also exhibit the same important technical and commercial features that are identified for the case studies in this chapter. 

In a multiphase membrane reactor, the conversion of benzylpenicillin to 6-aminopenidllinic acid is performed. The type of microstructured reactor used is a fermentation reactor which contains the enzyme penicillin acylase immobilized on the wall of a hollow-fiber tube. The hollow-fiber tube extracts 6-aminopenicillinic acid at the same time selectively. Benzylpenicillin is converted at the outer wall of the hollow fiber into the desired product, which passes into the sweep stream inside the fiber where it can be purified, e.g. by ion exchange. The non-converted benzylpenicillin is recycled back through the reactor [84],... 

Hydroiysis Peniciiiins Hydrolysis reactions in an acidic medium. Mixtures of penicillins and 6-aminopenicillinic acid can be resolved. 

Aminopenicillinic acid (6-APA) is made from Penicillin G. The current fermentation approach gives a relatively pure aqueous solution containing a high concentration of Penicillin G. Solvent extraction is used to recover the product. However, ion exchange resins could be used to recover the product as well. The chemical method involves a very low temperature operation ( 40°G) and the use of several solvents (see Fig. 9.12). The waste stream will contain chlorinated solvents and organics. The biotechnology process is operated at room temperature and does not produce waste. The immobilization of the enzyme is still a research area. 

This exercise can also be done on Whatman LKCigF, 20 X 20-cm preadsorbent plates (Whatman TLC Technical Series, Volume 3). The six individual penicillins are prepared as 1-mg/ml solutions in methanol, and 5 pi of each sample is applied to separate origins on the plate. The mobile phase is methanol-H20-1% NaHC03 (45 55 0.8), and the plate is developed for a distance of 10 cm from the origin in a glass tank that has been preequiUbrated with the mobile phase for 10 min. Time of development is about 70 min. The spots are detected with iodine vapor and the approximate Rf values of the separated penicillins are as follow cloxacillin, 0.18 oxacillin, 0.22 penicillin G, 0.34 methicillin, 0.41 ampicillin, 0.66 and 6-aminopenicillinic acid, 0.82. 

Reaction mixture 6-aminopenicillin acid + carboxylic acid... 

For the extraction and subsequent derivatization of penicillin G from a fermentation broth, Scheper et al. (48) utilized an ELM system containing the enzyme pencillin acylase in the internal phase to convert the extracted penicillin G to the products 6-aminopenicillinic acid and phenylacetic acid. Recently, Lee and Lee (49) and Mok et al. (50) successfully performed the ELM extraction of this penicillin with sodium carbonate in the internal phase. Mok et al. (50) gave an ELM system for this extraction, which is shown in Table X. They obtained extraction eflBciencies between 80% and 95% for emulsion/feed ratios ranging from 0.167 to 0.2 and an internal phase concentration of greater than 9 times the initial concentration in the external feed phase. In addition, extraction of peptides was investigated recently (51). 

Aminopenicillins amoxicillin a-mox-i-sil -in amoxicillin and clavulanate acid a-mox-i-sil -in/ klah-view-lan -ate Amoxil, Trimox, Wymox, generic Augmentin Same as penicillin G Same as penicillin G... 

A thorough discussion of the mechanisms of absorption is provided in Chapter 4. Water-soluble vitamins (B2, B12, and C) and other nutrients (e.g., monosaccharides, amino acids) are absorbed by specialized mechanisms. With the exception of a number of antimetabolites used in cancer chemotherapy, L-dopa, and certain antibiotics (e.g., aminopenicillins, aminoceph-alosporins), virtually all drugs are absorbed in humans by a passive diffusion mechanism. Passive diffusion indicates that the transfer of a compound from an aqueous phase through a membrane may be described by physicochemical laws and by the properties of the membrane. The membrane itself is passive in that it does not partake in the transfer process but acts as a simple barrier to diffusion. The driving force for diffusion across the membrane is the concentration gradient (more correctly, the activity gradient) of the compound across that membrane. This mechanism of... 

In a recent study, the bacterial populations contaminating the upper gut in SIBO patients and their antibiotic susceptibility were determined. Amoxicillin-clavulanic acid and cefoxitin were effective against >90% of anaerobic strains, while aminopenicillins, cephalosporins and cotrimoxazole were effective against the microaerophilic population. Erythromycin, clindamycin and rifampicin were ineffective. Data on metronidazole and fluoroquinolones are not available [32]. 

Tolerances for these compounds are generally O-.Ol ppm except for penicillin G in cattle (.05 ppm) and cephapirin in edible tissue (0.1 ppm) and milk (.02 ppm) (70). Many chromatographic methods have been described for determination of these compounds in clinical applications, but these methods are not sufficiently sensitive for residue analysis. The summary of methods in Table II includes one GLC (71), five TLC (72-76), and five HPLC methods (77-81). Four of the TLC methods use detection by bioautography. Three HPLC methods have been described for milk (77-79) and two for tissue (80,81). The HPLC methods described by Moats C7 ,80) and by Munns et al (77) are satisfactory for any penicillin with a neutral side-chain and this may be true with the procedure of Terada, et al. (81). The procedure of Terada and Sakabe (79) is also satisfactory for the aminopenicillin, amplclllin. The method of Munns et al (77) can also be used to detect the corresponding penicilloic acid metabolites. 

Clavulanic acid and sulbactam An addition of beta-lactamase inhibitors, such as clavu-lanic acid (32.1.1.35) and sulbactam (32.1.1.36) to penicillins or to aminopenicillins of a broad spectrum of action significantly expands their antimicrobial spectrum. 

In combination with beta-lactamase inhibitors, like e.g. clavulanic acid, the aminopenicillins can be effective also against beta-lactamase-producing organisms. 

Apart from the syntheses of peptides, the Nps group has found useful application in the preparation of aminopenicillins,t l of O-sulfated (3-lactam hydroxamic acids,t and of the (3-lactone antibiotic (-f)-obafluorin.t l... 

The mechanism of absorption must always be evaluated when a sustained-release dosage form is considered. A drug that is passively absorbed throughout the GI tracts is an ideal candidate for sustained release. Drugs such as riboflavin, folic acid, aminopenicillins, amino-p-lactams and nucleoside analogs, which have windows of absorption due to site-specific and/or active transport processes, may have incomplete bioavailability when formulated in oral, sustained-release dosage forms. 

The use of azido acids for the introduction of aminoacyl groups eliminates the need of protecting the amino group during the acylation. The azidoacyl derivatives obtained are reduced directly to the aminoacyl ones. This method was used in the preparation of aminopenicillins (19) from azidoacyl chlorides and 6-aminopenicillanic acid, Azido-... 

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