Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

The Penicillins

Other antibiotics that interfere with cell-wall synthesis are cycloserine 5.11) (see Section 9.4.3), vancomycin, bacitricin, and many substances chemically closer to penicillin, all discussed in Section 13.2. [Pg.556]

Many penicillins have been isolated from the liquor in which active strains of [Pg.556]

Penicillium notatum are growing (see Section 6.3.1). They have the general structure 13.4a) differing only in the nature of the side-chain. The variety known as benzylpenicillin soon became the standard, and is always to be understood when penicillin is specified 5.13 13.4b).  [Pg.557]

Studies on the inactivation of benzylpenicillin have shown that this substance has a strong preference for acylating j8-aminomercaptans, much less affinity for other amines, and none for other mercaptans. The product [e.g. 13.6) from j8-mercaptoethylamine] is acylated on the amino-group. The function of the mercapto-groups seems to be to form a hydrogen bond with the oxygen atom of the lactam and hence increase the polarization of the C=0 bond in the penicillin. [Pg.557]

Experiments with penicillin show that resistant strains of staphylococci, even those that produce no penicillinase, take up no penicillin from solution, but susceptible strains of various species combine with from 200 to 750 molecules per cell. This amount is held tightly, cannot be washed away, and does not exchange with non-radioactive penicillin (Rowley et al., 1950 Maass and Johnson, 1949). The first molecules of penicillin are bound by inert material but, when this is saturated, the penicillin combines covalently with a receptor playing a key role in the biosynthesis of cell wall. Mammalian cells do not take up penicillin, but the bacterial cell binds it in less than 2 minutes. The penicillinbinding component is on the exterior, in the cytoplasmic membrane where the cell wall is synthesized. This component occurs in a phospholipid-containing fraction of staphylococci (Cooper, 1956). [Pg.557]

Cycloserine (5.4) (see Section 9.4), vancomycin (Chatterjee and Park, 1964), and bacitracin (Abraham, 1957) also lyse bacteria by interfering with the synthesis of wall materials. The last two antibiotics are discussed in Section 12.2. [Pg.449]

The early workers with penicillin were inconvenienced by its proneness [Pg.449]

Benzylpenicillin is hydrolysed, to the corresponding penicilloic acid (i2.7)y by alkali, cupric ions, or p-lactamase (usually called penicillinase), and to penillic acid, and penicillamine (11.21), In natural biosynthesis it is formed by the condensation of 6-penicillamine, D-valine, and phenyl-acetic acid. The presence of the highly strained four-membered lactam ring in penicillin makes it a powerful, but specific, acylating agent. This ring readily opens between C-7 and the nitrogen atom. [Pg.450]

Pipcnu illin r 4 Ethyl 2.3 diox V l piper.vinylcarbonyl amino )bmzylpcnicilliR [Pg.303]

Two other developments have provided additional means for making new penicillins. A group of British scientists, Batchelor et al., reported the isolation of 6-aminopenicil-lanic acid from a culture of P. chrysogenum. This compound can be converted to penicillins by acylation of the 6-amino group. Sheehan and Ferris provided another route to synthetic penicillins by converting a natural penicillin, such as penicillin G potassium, to an intermediate (Fig. 10-1), from which the acyl side chain has been cleaved and which then can be treated to form biologically active penicillins with a variety of new side chains. By these procedures, new penicillins, superior in activity and stability to those formerly in wide use, were found, and no doubt others will be produced. The first commercial products of these research activities were phenoxyethylpenicillin (phenethicillin) (Fig. 10-2) and dimethoxyphenylpenicillin (methicillin). [Pg.304]

The early commercial penicillin was a yellow to brown amorphous powder that was so unstable that refrigeration was required to maintain a reasonable level of activity for a short time. Improved purification procedures provided the white crystalline material in use today. Crystalline penicillin must be protected from moisture, but when kept dry, the salts will remain stable for years without refrigeration. Many penicillins have an unpleasant taste, which must be overcome in the formation of pediatric dosage forms. All of the [Pg.304]

Acid-calalyzcd degradation in the stomach contributes strongly to the poor oral ab.sorplian of penicillin. Thus, efforts to obtain penicillins with improved pharmacokinetic and microbiological properties have foensed on acyl functionalities that would minimize. sensitivity of the j laclani ring to acid hydrolysis while maintaining antibacterial activity. [Pg.305]

Some bacteria, in particular most species of Gram-negative bacilli, arc naturally resi.stont to (he action of penicillins. Other normally sensitive species can develop penicillin resistance (either through natural. selection of resistant individ- [Pg.305]


Antibiotics. Solvent extraction is an important step in the recovery of many antibiotics (qv) such as penicillin [1406-05-9] streptomycin [57-92-17, novobiocin [303-81-1J, bacitracin [1405-87-4] erythromycin, and the cephalosporins. A good example is in the manufacture of penicillin (242) by a batchwise fermentation. Amyl acetate [628-63-7] or -butyl acetate [123-86-4] is used as the extraction solvent for the filtered fermentation broth. The penicillin is first extracted into the solvent from the broth at pH 2.0 to 2.5 and the extract treated with a buffet solution (pH 6) to obtain a penicillin-rich solution. Then the pH is again lowered and the penicillin is re-extracted into the solvent to yield a pure concentrated solution. Because penicillin degrades rapidly at low pH, it is necessary to perform the initial extraction as rapidly as possible for this reason centrifugal extractors are generally used. [Pg.79]

Certain factors and product precursors are occasionally added to various fermentation media to iacrease product formation rates, the amount of product formed, or the type of product formed. Examples iaclude the addition of cobalt salts ia the vitamin fermentation, and phenylacetic acid and phenoxyacetic acid for the penicillin G (hen ylpenicillin) and penicillin V (phenoxymethylpenicillin) fermentations, respectively. Biotin is often added to the citric acid fermentation to enhance productivity and the addition of P-ionone vastly iacreases beta-carotene fermentation yields. Also, iaducers play an important role ia some enzyme production fermentations, and specific metaboHc inhibitors often block certain enzymatic steps that result in product accumulation. [Pg.180]

P-Lactams. AH 3-lactams are chemically characterized by having a 3-lactam ring. Substmcture groups are the penicillins, cephalosporias, carbapenems, monobactams, nocardicias, and clavulanic acid. Commercially this family is the most important group of antibiotics used to control bacterial infections. The 3-lactams act by inhibition of bacterial cell wall biosynthesis. [Pg.474]

The mechanism of antibacterial activity is through inhibition of gram-positive bacterial cell-wall synthesis thus, the penicillins are most effective against actively multiplying organisms. Because mammalian cells do not have a definitive cell-wall stmcture as do bacteria, the mammalian toxicity of the penicillins is low. Allergic phenomena in patients following sensitization may occur. [Pg.403]

The penicillins as natural and semisynthetic agents are used primarily against susceptible Pasteurella sp., staphylococci, streptococci, clostridia, and CoTynebacterium sp. Penicillin is widely used for therapeutic purposes against these organisms and in animal feeds as a growth promoter. The latter effect is considered to be a result of subtie and reversible effects on the gastrointestinal microflora. [Pg.403]

In the period up to 1970 most P-lactam research was concerned with the penicillin and cephalosporin group of antibiotics (1). Since that time, however, a wide variety of new mono- and bicychc P-lactam stmctures have been described. The carbapenems, characterized by the presence of the bicychc ting systems (1, X = CH2) originated from natural sources the penem ring (1, X = S) and its derivatives are the products of the chemical synthetic approach to new antibiotics. The chemical names are 7-oxo-(R)-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxyhc acid [78854-41-8] CyH NO, and 7-oxo-(R)-4-thia-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxylic a.cid [69126-94-9], C H NO S, respectively. [Pg.3]

Fermentation. The commercial P-lactam antibiotics which act as starting material for all of the cephalosporins ate produced by submerged fermentation. The organisms used for the commercial production of the penicillins and cephalosporins ate mutants of PenicU/in chTysogenum and Cephalosporium acremonium respectively (3,153,154). Both ate tme fungi (eucaryotes). In contrast, the cephamycins ate produced by certain species of procaryotic Streptomyces including Streptomyces clavuligerus and Streptomyces lipmanii (21,103). [Pg.31]

Isolation. Isolation procedures rely primarily on solubiHty, adsorption, and ionic characteristics of the P-lactam antibiotic to separate it from the large number of other components present in the fermentation mixture. The penicillins ate monobasic catboxyHc acids which lend themselves to solvent extraction techniques (154). Pencillin V, because of its improved acid stabiHty over other penicillins, can be precipitated dkecdy from broth filtrates by addition of dilute sulfuric acid (154,156). The separation process for cephalosporin C is more complex because the amphoteric nature of cephalosporin C precludes dkect extraction into organic solvents. This antibiotic is isolated through the use of a combination of ion-exchange and precipitation procedures (157). The use of neutral, macroporous resins such as XAD-2 or XAD-4, allows for a more rapid elimination of impurities in the initial steps of the isolation (158). The isolation procedure for cephamycin C also involves a series of ion exchange treatments (103). [Pg.31]

The cephalosporins generally cause few side effects (80,132,219—221). Thrombophlebitis occurs as a result of intravenous administration of all cephalosporins. Hypersensitivity reactions related to the cephalosporins are the most common side effects observed, but these are less common than found with the penicillins. Clinically only about 5—10% of patients with allergic reactions to the penicillins manifest the same reactions to the cephalosporins, and data would contradict any tme cross-reactivity to cephalosporins in patients who have previously reacted to penicillin (80,132,219). [Pg.39]

Penam P-Lactamase Inhibitors. Penam is the trivial name given derivatives of the penicillin nucleus (31) the chemical name of which is 4-thia-l-a2abicyclo[3.2.0]heptane. Table 6 gives activity data for a diverse group of penams. The report that 6-P-bromopeniciU.anic acid [26631-90-3] [2(3)-(2a,5a,6P)]-6-bromo-3,3-dimethyl-7-oxo-4-thia-l-a2abicyclo[3.2.0]heptane-2-carboxyhc acid, (31, R = Br, R =H, R" = R " = CH3) a potent... [Pg.54]

All of the naturally-occurring monobactams discovered as of this writing have exhibited poor antibacterial activity. However, as in the case of the penicillins and cephalosporins, alteration of the C-3 amide side chain led to many potent new compounds (12). Furthermore, the monobactam nucleus provides a unique opportunity to study the effect of stmctural modifications at the N-1 and C-4 positions of the a2etidinone ring on biological activity. In contrast to the bicycHc P-lactams, these positions on the monocyclic ring system are readily accessible by synthesis. [Pg.62]

Spectral Characteristics. The iafrared stretching frequency of the penicillin P-lactam carbonyl group normally occurs at relatively high frequencies (1770 1815 cm ) as compared to the absorptions for the secondary amide (1504-1695 cm ) and ester (1720-1780 cm ) carbonyl groups. [Pg.74]

Fig. 1. The penicillin thiazolidine ring (a) open conformation (b) closed conformation. Fig. 1. The penicillin thiazolidine ring (a) open conformation (b) closed conformation.
Chemical Modification. Chemical modification of most positions in the penicillin nucleus have been carried out and these are summarized in Table 4. Apart from acylation of 6-APA, few of these modifications have proven profitable in terms of improving the biological properties of the derived penicillins. However, one of the modifications that has led to beneficial properties is substitution at the 6a-position. [Pg.78]

The penicillins in general, ate renowned for their lack of toxicity. The most common adverse effect of the use of penicillins is an allergic reaction which can change from a mild rash to fatal anaphylactic shock in rate cases. AH penicillins cross the placenta and ate excreted in maternal milk. However, the relative freedom from toxicity tenders these compounds valuable agents during pregnancy and lactation. [Pg.83]

The second most important group of immobilized enzymes is stiU the penicillin G and V acylases. These are used in the pharmaceutical industry to make the intermediate 6-aminopenici11anic acid [551-16-6] (6-APA), which in turn is used to manufacture semisynthetic penicillins, in particular ampicilHn [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 ... [Pg.291]

The interaction of acid chlorides (167 X = Cl) with imines in the presence of bases such as triethylamine may involve prior formation of a ketene followed by cycloaddition to the imine, but in many cases it is considered to involve interaction of the imine with the acid chloride to give an immonium ion (168). This is then cyclized by deprotonation under the influence of the base. Clearly, the distinction between these routes is a rather fine one and the mechanism involved in a particular case may well depend on the reactants and the timing of mixing. Particularly important acid chlorides are azidoacetyl chloride and phthalimidoacetyl chloride, which provide access to /3-lactams with a nitrogen substituent in the 3-position as found in the penicillins and cephalosporins. [Pg.260]

The penicillins are a class of compound having the general structure (1). Because of their unique effectiveness in the treatment of bacterial infections in humans, these compounds have been investigated intensively from the chemical, microbiological and clinical points of view since about 1940. The early history of these developments (see especially B-80MI51100, B-49MI51100) contains the following pivotal studies ... [Pg.299]


See other pages where The Penicillins is mentioned: [Pg.48]    [Pg.298]    [Pg.314]    [Pg.861]    [Pg.862]    [Pg.952]    [Pg.178]    [Pg.182]    [Pg.257]    [Pg.473]    [Pg.475]    [Pg.476]    [Pg.4]    [Pg.8]    [Pg.9]    [Pg.21]    [Pg.22]    [Pg.22]    [Pg.28]    [Pg.32]    [Pg.38]    [Pg.39]    [Pg.62]    [Pg.72]    [Pg.72]    [Pg.72]    [Pg.72]    [Pg.75]    [Pg.76]    [Pg.80]    [Pg.81]    [Pg.253]   


SEARCH



Biosynthesis of the Penicillins

Florey and the Penicillin Production Line

Look up the names of both individual drugs and their drug groups to access full information Penicillin G

Look up the names of both individual drugs and their drug groups to access full information Penicillins

Penicillin Inhibits the Transpeptidation Reaction

Role of the Side Chain in Penicillin Allergy

Semi-Synthetic Penicillins and the Growing Problem of Resistance

Structure of the penicillins

The Discovery of Penicillin

The biosynthesis of penicillins and cephalosporins

The penicillinase-resistant penicillins are oxacillin, cloxacillin, dicloxacillin, methicillin, and nafcillin

© 2024 chempedia.info