Penidllin

Another synthesis avoids the isolation of 6-APA and starts directly with penidllin G. Reaction with chloromethyl pivalate gives its pivaloyloxymethyl ester. This reacts with PCI5 to an imidoyl chloride which may be solvolyzed with propanol. The add chloride of (R)-... 

The P. notatum took up the P-phenyl ethylamine, converted it to p-phenylacetate, which was subsequently attached to the 6-amino group of penirillanic add to give benzyl penicillin (penidllin G). We can represent this process by ... 

Previous penidllins had aliphatic groups attached to the 6-amino p>enidllanic add moiety. Penicillin G has many advantages over the aliphatic derivatives, eg it is more easily crystallised and it is more stable. 

The obvious way is to indude p-phenylacetic add or p-phenylethylamine in cultures. Indeed, when (J-phenylacetic add was added to cultures grown in CSL, the yields of penidllin were enhanced further. Typical yields were 100-150 ig ml 1. 

In pwindple, by adding derivatives of acetic add to culture media, we might be able to produce a wide range of penidllins- This strategy was adopted, eg indusion of phenoxyacetic add led to the production of penidllin V ... 

Figure 6.14 Enzymatic side chain cleavage of penicillins. 6-Aminopenicillanic acid, a valuable intermediate for the production of various semi-synthetic penicillins, can be obtained through enzyme-mediated hydrolysis of the phenylacety group of penicillin G or the phenoxyacetyl group of penicillin V. The active site of the enzyme recognises the aromatic side chain and the amide linkage, rather than the penidllin nucleus. Chemical entitles other than penicillins are therefore often good substrates, as long as they contain the aromatic acetamide moiety.

It was almost immediately recognised that the deacylated product, 7-aminocephalosporanic add (7-ACA, Figure 6.16), would be of similar importance as was 6-APA in the development of new penidllins. However, 7-ACA, the cephalosporin equivalent of 6-APA, could not be found in fermentations of Cephalosporin acremonium. In Figure 6.15 we have shown that penicillin acylase hydrolyses the acyl residue from natural cephalosporins. Up to a point this is true. These acylases will, however, only work with a limited range of acyl residues. It now seems that nature does not provide for acylases or transacylases that have the capacity to remove or change the D-a-aminoadipyl side chain of cephalosporin C efficiently in a single step. Widespread search for such an enzyme still remains unsuccessful. 

Natural penidllins-penidllin Gand penidllin V Penidllinase-resistant penidllin—cioxadllin, didoxadllin, nafdllin Aminopenidllins-ampidllin, amoxidllin, bacampidllin Extended-spectrum penidllins—mezlodllin, piperacillin, ticardllin... 

Risk for Impaired Skin Integrity related to adverse reaction to penidllin... 

Vancomycin therapy recommended only for patients unable to tolerate penidllin or ceftriaxone therapy... 

R. B. Woodward, The Chemistry of Penidllin , Princeton University Press, Princeton, 1948. 

Penicillin G Benzathine 55 Penicillin G Potassium 55 Penicillin G Procaine 55 Penidllin V 55 Pentam 55 Pentamidine 55 Pentasa 47 Pentazodne 82 Pentids 55 Pentosan 55 Pentoxifylline 55 Pepcid... 

The indications for penidllin-3-lactamase inhibitor combinations are empirical therapy for infections caused by a wide range of potential pathogens in both immunocompromised and immunocompetent patients and treatment of mixed aerobic and anaerobic infections, such as intra-abdominal infections. Doses are the same as those used for the single agents except that the recommended dosage of piperacillin in the piperacillin-tazobactam combination is 3 g every 6 hours. Adjustments for renal insufficiency are made based on the penicillin component. 

PhAc APA Penidllin G 80 ZnS04 used as counter-ion to favor produd predpitation. ... 

J) Degradation of readily available penidllin derivatives (cf. Sedion 5.09.3.3.4). 

Drugs/Hormones Chloramphenicol, penidllin, sulfamethazine, growth hormones... 

E. De Vroom, The central role of penidllin acylase in antibiotics production, Chimica Oggi 1999, 17, 65-68. 

J. N. Levy, and M. Stukus, Side chain selectivity and kinetics of penidllin G amidase in acylating a cis-racemic / -lactam intermediate in the synthesis of Loracarbef, New J. Chem. 1994, 38, 425 434. 

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