Benzylpenicillin penicillin production

PhCHa benzylpenicillin = penicillin G (usual fermentation product)... 

Penicillin was the first antibiotic to find practical use in medicine. Commercial production began in the early 1940s and benzylpenicillin (penicillin G), one of several natural penicillins that differ in the R group boxed in the structure above, became one of the most important of all drugs. Most effective against gram-positive bacteria, at higher con-... 

Many of the medical products reviewed here find multiple applications. Thus procaine compounded with benzylpenicillin, penicillin G is an antimicrobial veterinary drug, approved in the US as a postexposure prophylaxis following inhalation of anthrax, providing that the strains do not have penicillin resistance. 

Semisynthetic. In 1959, scientists at Beecham Researeh Laboratories sueceeded in isolating the penicillin nucleus, 6-aminopenicillanie aeid (6-APA Fig. 5.1 A R represents H). During the commercial production of benzylpenicillin, phenylacetic (phenylethanoic) acid (C6H5.CH2.COOH) is added to the medium in whieh the Penicillium mould is growing (see Chapter 7). This substance is a precursor of the side... 

The manufacture of benzylpenicillin (penieillin G, originally just penicillin ) is chosen as a model for the antibiotic production process. It is the most renowned of antibioties and is the first to have been manufactured in bulk. It is still universally prescribed and is also in demand as input material for semisynthetic antibiotics (Chapter 5). Developments associated with the penicillin fermentation process have been a significant factor in the development of modem bioteehnology. It was a further 30 years, i.e. not until the 1970s, before there were signifieant new advances in industrial fermentations. 

No single product can exemplify all the important features of antibiotie manufaeture. Benzylpenicillin is a /Mactam. Brief aeeounts are given of the manufaeture of two other /3-lactams, penicillin V (phenoxymethylpenicillin) and cephalosporin C, to illustrate further key points. 

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],... 

Adverse CNS effects occur when the procaine portion of the procaine benzylpenicillin (procaine penicillin) formulation is given intravascularly. The signs of toxicity include hyperexcitability, muscle tremors, ataxia, apnea and cardiac arrest. There is no specific treatment for procaine toxicity one can only attempt to prevent the horse from injuring itself and others imtil the effects of the procaine wear off. The CNS reaction can be prevented by pretreatment with diazepam. The solubility of the procaine fraction of procaine benzylpenicillin (procaine penicillin) formulations increases with increasing ambient temperature, so these products should be stored in a cool place to reduce the risk of reactions. Procaine is a common cause of positive drug tests in racehorses and other performance horses. Procaine benzylpenicillin (procaine penicillin) should be avoided in these animals. 

It is possible to convert penicillin V or benzylpenicillin to a cephalosporin by chemical ring expansion. The first-generation cephalosporin cephalexin, for example, can be made in this way. Most cephalosporins used in clinical practice, however, are semi-synthetics produced from the fermentation product cephalosporin C. 

In attempts to synthesize the oxazolone-thiazolidine of formula 2, by condensing the dimethylcysteine with the appropriate oxazolone, it was noted that the reaction products always showed a very low antibiotic activity though they had properties similar to penicillin. However, at first all attempts to concentrate the activity by various fractionation procedures, including chromatography, failed and it was doubted in many circles whether or not the activity could really be due to penicillin. This uncertainty was resolved by du Vigneaud and co-workers (S) who employed the method of countercurrent distribution (see Chapter I), and were able to isolate a crystalline sodium salt from the mixture. This salt had full antibiotic activity and was identical in every respect with naturally-occurring benzylpenicillin. The synthetic acid was present in the reaction mixture at a concentration of only about 0.1%. 

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