Benzylpenicillin structure

Confirmation of the structure of benzylpenicillin by X-ray diffraction studies (B-49MI51101). 

The nomenclature of penicillins requires special comment. Compound (2) can be named as follows (a) penicillin G (b) benzylpenicillin (note that the term penicillin may refer to the compound class (1), to the structural fragment (3) or, especially in the medical literature, to compound (2) itself) (c) 6/3-phenylacetamidopenicillanic acid (d) 2,2-dimethyl-6/3-phenylacetamidopenam-3a -carboxylic acid (e) (2S,5i ,6i )-3,3-di-methyl-7-oxo-6-(2-phenylacetamido)-4-thia-l-azabicyclo[3.2.0]heptane-2-carboxylic acid and (f) [2S-(2a,5a,6/3)]-3,3-dimethyl-7-oxo-6-[(phenylacetyl)amino]-4-thia-l-azabicyclo-[3.2.0]heptane-2-carboxylic acid. The numbered system shown in (2) is the one most commonly used in the penicillin literature and will be used in this chapter note that different number is used when (2) is named according to (e) and (f) above. 

The early investigations of the reactions of the penicillin class of compounds were largely of a degradative nature, and were primarily associated with structure elucidation. These have been discussed in detail (B-49MI51102) and some of the principal transformations are outlined in Schemes 2, 3 and 4 using benzylpenicillin as an example. Some of these reactions will be discussed in greater detail later in this section. 

Sjsj2 reaction and, 377-378 Benzylic radical, resonance in, 578 spin-density surface of, 578 Benzylpenicillin, discovery of, 824 structure of, 1 Benzyne, 575... 

The building blocks for the biosynthesis of benzylpenicillin are three amino acids, a-aminoadipic acid, cysteine and valine, and PAA. The amino acids condense to a tripeptide, ring closure of which gives the penicillin ring structure with an cu-aminoadipyl side-chain, isopenicillin N. The side-chain is then displayed by a phenylacetyl group from PAA to give benzylpenicillin. 

The (5-lactam antibiotics are now so extensively described that we cannot attempt to summarize the literature. Since our emphasis is on sulfur, we note that the sulfur atoms of the thiazolidine or dihydrothiazine rings derive from a common tripeptide, 8-(L-a-aminoadipyl)-L-cysteinyl-D-valine 1, ACV or Arnstein tripeptide . ACV is converted to a (5-lactam structure, isopenicillin N 2 and thereafter, the two pathways diverge, i.e. to benzylpenicillin 3 or to cephalosporin C 4 (Scheme 1). There have been extensive studies of the genes and enzymes involved in (5-lactam biosynthesis.18,19... 

Penicillin and cephalosporin antibiotics are usually classed as P-lactam antibiotics, since their common feature is a lactam function in a four-membered ring, typically fused to another ring system. This second ring takes in the P-lactam nitrogen atom and also contains sulfur. In the case of penicillins, e.g. benzylpenicillin, the second ring is a thiazolidine, and in the cephalosporins, e.g. cephalosporin C, this ring is a dihydrothiazine. What is not readily apparent from these structures is that they are both modified tripeptides and their biosyntheses share a common tripeptide precursor. 

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-... 

Before interest developed in the structure of penicillin, the imidazo[5,1-b ]thiazole ring system was unknown, and even today, almost all of the examples which have been described are those prepared in connection with penicillin studies. Very mild acidic hydrolysis converts benzylpenicillin methyl ester (293) into benzylpenicillic acid (294) by a mechanism suggested... 

Since the first X-ray structure determination of benzylpenicillin potassium 42 (a penam) in 1949, the structures of a large number of -lactam antibiotics have been reported . Table 2 shows the limiting values of the -lactam ring dimensions in a range of penicillin derivatives . More recent X-ray studies on the penicillin and cephalosporin families of antibiotics have been summarized. 

Benzylpenicillin (1942) is produced by growing one of the penicillium moulds in deep tanks. In 1957 the penicillin nucleus (6-amino-penicillanic acid) was synthesised and it became possible to add various side-chains and so to make semisynthetic penicillins with different properties. It is important to recognise that not all penicillins have the same antibacterial spectrum and that it is necessary to choose between a number of penicillins just as it is between antimicrobials of different structural groups, as is shown below. 

Penicillin (or benzylpenicillin) (32a) (R = CH2Ph) was first dicovered by Sir Alexander Fleming in 1929, who isolated the antibiotic from the fungal strain Penicillium notatum (see Introduction, p. 4). Penicillin is valuable to combat bacterial infections in man and animals. It was first manufactured commercially in 1945 and the first semisynthetic penicillins were introduced in 1954. The penicillins (32) have a common structural feature, namely a p-lactam ring fused to the... 

Zhao Z, Baldo BA, Rimmer J beta-Lactam allergenic determinants fine structural recognition of a cross-reacting determinant on benzylpenicillin and cephalothin. 

Most of the structural work was done with benzylpenicillin, CicHijO SNjNa. It is a sodium salt. The free acid is a strong monobasic acid which has not been crystallized. It is unstable to acid or alkali and most stable in solution at a pg of 6. The free acid is relatively stable in dry ether solution. 

The accepted structural formula of benzylpenicillin is shown in formula (1). j,... 

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