Structure of the penicillins

Geariy these enzymes are not highly specific, since they do not distinguish between the ring structures of the penicillins and those of the cephalosporins. 

W Bruns, J Hoppe, H Tsai, HJ Bruning, F Maywald, J Collins, H Mayer. Structure of the penicillin acylase gene from Escherichia coir, a periplasmic enzyme that undergoes multiple proteolytic processing. J Mol Appl Genet 3 36-44, 1985. 

As with the penicillins, hypersensitivity reactions are the most common systemic adverse events caused by cephalosporins. Maculopapular rash, urticaria, fever, bron-chospasm,and anaphylaxis have been associated with the use of cephalosporins.Because the molecular structure of the penicillins and the first-generation cephalosporins are similar, there is a risk in patients who are aUergic to penicillin to manifest aUergic cross-reactions when prescribed any of this gronp of cephalosporins. In contrast, the risk of cross-reactivity between the penicUUns and the second-, third-, and fonrth-generation cephalosporins has been overestimated, and patients with a previons aUergic... 

Table 10-2. shows the general structure of the penicillins Jill lelates the structure of the more familiar ones to their laioun designations. 

The structure of the penicillins (3.1) was established in the days before spectroscopic methods were routinely applied to structure determination. The degradative evidence for the structure of the penicillins is best understood if it is realized that the central carbon (C-5) of the thiazolidine ring in the core of the structure is a masked aldehyde and, secondly, that the p-lactam is a strained four-membered ring in which the lactam does not behave as a typical amide. The shape of the ring precludes the normal amide resonance and hence hydrolysis of the lactam takes place more easily than would be expected for an amide. This hydrolysis then places a carboxylic acid in the p-position to the masked aldehyde so that decarboxylation of a p-keto acid can occur. 

The chemical structure of the penicillins remained in doubt throughout the war years despite considerable efforts and much speculation by a group led by Karl Folkers at Merck, and the Oxford group comprising Robert Robinson, Chain, Abraham and others. One of the major problems was that the initial microanalysis had not revealed the presence of a sulfur atom, and it was not until penicillamine was revealed in 1943 as the major acid degradation products of all the known penicillins that realistic structures could be... 

Chain, E. B. The Chemical Structure of the Penicillins. Nobel Lecture, March 20, 1945. Available online at http //nobelprize.org/medicine/laureates/1945/chain lecture, pdf (accessed on October 23, 2005). 

How would you establish the structure of the Penicillins as per the following steps ... 

Some idea of the difficulties in determining the structure of the penicillins is illustrated by the conversion of benzylpenicillin in acid solution, first to benzyl-penillic acid and then to benzylpenilloic acid. 

Penicillenic acids are readily formed in aqueous solutions of penicillins by an intramolecular rearrangement, as described in Sect. C.I.l.a, and they are present in small amounts in almost all penicillin preparations (e.g., Meulenhoff 1965 Seitzinger 1973 Brandt et al. 1974). The rate of formation of penicillenic acid increases strongly with decreasing pH of the penicillin solutions and it shows a high dependence on the inductive effect of the side chain structure of the penicillins (Schwartz and Wu 1966). The compounds are highly reactive with proteins and... 

Elucidation of the structure of the penicillin nucleus involved extensive degradation studies and X-ray analysis. Reaction of a penicillin under hydrolytic conditions followed by further degradation with mercuric chloride was shown to give D-penicillamine (46) and the penilloaldehyde (47). From this evidence it was concluded that the primary hydrolysis... 

However, the structure of the penicillin (and other P-lactams) resembles the D-alanyl-D-alanine moiety (Fig. 22.4) and can therefore react with the transpeptidase enzyme to form a covalent ester bond. 

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