6-Aminopenicillanic acid Ampicillin

Aminopenicillanic acid, ampicillin and carbenicillin are readily distinguished separation of the other penidllins tested is only marginal Ref... 

Aminopenicillanic acid Amoxicillin Ampicillin Azidocillin Aziocillin... 

Aminopenicillanic acid (6APA), 437 Aminopi/rinG, 262 Aminorex, 265 Amiquinsin, 363 Amoproxan, 91 Amoxapine, 428 Amphecloral, 48 Amphetamine, 47 Amphetaminil, 48 Ampicillin, 437, 438 Ampyzine, 298 Amquinate, 370 Anagram, 235... 

The second most important group of immobilized enzymes is still the penicillin G and V acylases. These are used in the pharmaceutical industry to make the intermediate 6-aminopenicillanic acid [551-16-6] (6-APA), which in turn is used to manufacture semisynthetic penicillins, in particular ampicillin [69-53-4] and amoxicillin [26787-78-0]. This is a remarkable example of how a complex chemical synthesis can be replaced with a simple enzymatic one ... 

The natural penicillins, primarily G and V, have a relatively narrow spectrum. They act mostly on gram-positive organisms. The fact that proper selection of precursors could lead to new variations in the penicillin side chain offered the first source of synthetic penicillins. Penicillin V, derived from a phenoxy-acetic acid precursor, attracted clinical use because of its greater acid tolerance, which made it more useful in oral administration. Also, the widespread use of penicillin eventually led to a clinical problem of penicillin-resistant staphylococci and streptococci. Resistance for the most part involved the penicillin-destroying enzyme, penicillinase, which attacked the beta-lactam structure of the 6-aminopenicillanic acid nucleus (6-APA). Semisynthetic penicillins such as ampicillin and carbenicillin have a broader spectrum. Some, such as methicillin, orafi-cillin, and oxacillin, are resistant to penicillinase. In 1984, Beecham introduced Augmentin, which was the first combination formulation of a penicillin (amoxicillin) and a penicillinase inhibitor (clavulanic acid). Worldwide production of semisynthetic penicillins is currently around 10,000 tons/year, the major producers are Smith Kline Beecham, DSM, Pfizer, and Toyo Jozo. 

Penicillin G as well as approx. 4 kt a-1 of penicillin V are enzymatically hydrolyzed into the -lactam nucleus 6-aminopenicillanic acid (6-APA), which is the building block for the semisynthetic penicillin antibiotics ampicillin and amoxycillin [121] (see Fig. 8.23). Part of the penicillin G is converted into 7-aminodesa-cetoxycephalosporanic acid (7-ADCA, 3 kt a-1), which is the intermediate for the semisynthetic cephalosporins cephalexin and cefadroxil [122]. 7-ADCA has traditionally been produced from penicillin G via a chemical ring expansion but an all-bio process has recently been started up by DSM. 

The major penicillin produced by P. chrysogenum in submerged culture was benzylpenicillin (PenG) (Figure 4), which was rather unstable under acid conditions and also deactivated by P-lactamases. However, the discovery of 6-aminopenicillanic acid (6-APA) also produced by P. chrysogenum, led to the preparation of new semisynthetic derivatives with improved stability e.g. methicillin, ampicillin and amoxycillin (Figure... 

Before it had been discovered that many penicillins could be made from appropi-ate tripeptides using IPNS, a semi-synthetic method was used to convert penicillin G (8.29) into 6-aminopenicillanic acid using a bacterial acylase followed by acylation of the free amino group. Examples of pharmaceutically important penicillins produced by this route include methicillin (8.41), ampicillin (8.42) and amoxycillin (8.43). There is a more important method of enzymically degrading penicillins than... 

Application of structurally similar lactams that are bactericidal and that are not hydrolysed by y0-lactamase [106]. A few semisynthetic penicillins fulfil these requirements. For instance, 6-amino-2,2-dimethyl-7-oxopenam-3-carboxylic acid (also known as 6-aminopenicillanic acid) can be prepared from a natural penicillin. This is then converted into a penicillin by acylation with another residue R. One of the most effective compounds of this type is ampicillin. 

Gonsalves LR, Femandez-Lafuente R, Guisan IM et al. (2002) The role of 6-aminopenicillanic acid on the kinetics of amoxiciUin enzymatic synthesis catalyzed by peniciUin G acylase immobilized onto glyoxyl agarose. Enzyme Microb Technol 31 464-471 Gorziglia G, Altamirano C, Conejeros R et al. (2002). Determination of kinetic parameters in the synthesis of ampicillin with immobilized penicillin acylase. Annals of the XV Chilean Congress of Chemical Engineering, Punta Arenas, October 2002, pp 107-112. 

Aminopenicillanic acid is treated to obtain the so-called. semisynthetic penicillins, of which the most well known are ampicillin and amoxycillin (see below). 

Davies RJ, Hendrick DJ, Pepys J (1974) Asthma due to inhaled chemical agents ampicillin, benzylpenicillin, 6-aminopenicillanic acid and related substances. Clin Allergy 4 227 Davis A, Sieglman SJ, Hewitt WH (1964) Neutropenia reaction to cephalothin therapy. An-timicrob Agents Chemother 1963 272... 

Aminopenicillanic acid Penicillin G Penicillin V Ampicillin Penicillin N... 

The most important penicillin derivative in terms of quantity is ampicillin, which is obtained by the reaction of 6-aminopenicillanic acid with the protected amine-group of D-phenylglycine (Dane process). 

Aminopenicillanic acid (6 APS) is an important precursor for the organic synthesis of new P. The compound itself has no antibiotic activity it is isolated as a fermentation product from cultures of Pen-cillium chrysogenum, or prepared by the enzymatic hydrolysis of benzylpenicillin. Thousands of new P. have been prepared by the acylation of 6 APS, but only a few of these are therapeutically useful, e.g Penicillin V is relatively stable to acid and is not hydrolysed in the stomach, so that it may be administered in tablet form Ampicillin (the aminophenyl-acetyl derivative of 6 APS), has a wider spectrum of activity than most other R, including activity against various Gram-negative bacteria (Typhus, E. coli, etc.). 

Patil and Day described the irreversible inactivation of /8-Iactamase from B. cereus 569/H with diazotization products of 6-aminopenicillanic acid and ampicillin. Preliminary experiments and jS-lactamasers and the diazotization products from many penicillins and cephalosporins showed no inactivation. 

The direct oxidation of 6-aminopenicillanic acid (5) or ampicillin (6) to their sulfoxides (7 and 8, respectively) could be accomplished either using peracetic acid on their p-toluenesulfonate salts (Micetich, 1976a) or with ozone (Spry, 1972). However, in the latter case, a mixture of the sulfoxide stereoisomers of 6-APA S R 4 1) (7 and 9) was obtained. 

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