Isolation Of 6-aminopenicillanic Acid Research Articles

The use of mother liquors after isolation of 6-aminopenicillanic acid as a substitute for phenylacetic acid

The use of mother liquors after isolation of 6-aminopenicillanic acid as a substitute for phenylacetic acid

Recent developments in the chemistry of penicillins.

The purpose of this review is to summarize the important developments in the chemistry of the penicillin molecule which have been reported in the scientific literature during the approximate period 1964 through 1972. The penicillins were intensively studied from a chemical point of view during the 1940’s and this work is discussed in detail in the penicillin monograph (36). The isolation of 6-aminopenicillanic acid in 1959 (16) led to the preparation of large numbers of penicillin derivatives in which the side chain at the 6-position of the penicillanic acid nucleus was modified. These efforts, which have been successful in introducing a number of important changes in the biological properties of the penicillin molecule, have been reviewed by PRICE (144) and others (55, 175, 72, 145, 2, 91). This aspect of penicillin chemistry will be dealt with only briefly in this review, and then only with reference to the chemistry involved. Recently, and particularly during the last four years (1969 through 1972), there have been increasing numbers of reports in which the chemistry of the penicillanic acid nucleus itself has been investigated, and it is principally to these studies that this review will address itself (see also 81, 129, 130, and 66).

Structure-activity relationships in semi-synthetic penicillins.

Investigation of the relationship between the antibacterial activity of penicillins and the chemical nature of the side chain began in earnest in 1957, when the isolation of 6-aminopenicillanic acid (6-APA) made possible the preparation of large numbers of N -substituted derivatives. Since that time some 1800 different penicillins have been prepared and studied in Beecham Research Laboratories, and the number examined throughout the world must amount to several thousands. The purpose of the present survey is to try to summarize the general patterns of structure-activity relationships which have emerged from these studies. 6-APA itself has only a low order of antibacterial activity, and the same applies to derivatives in which the amino group at position 6 is substituted by radicals other than acyl groups (figure 1). Hence it soon became clear that no advantage was to be gained from such considerable structural variations, and efforts were concentrated on preparing true penicillins containing acyl side-chains. Virtually all of these show considerable activity in vitro against at least some bacteria, but the spectrum of activity varies widely.

Clinical Evaluation of Nafcillin in Patients with Severe Staphylococcal Disease

NAFCILLIN, 6-(2-ethoxy-1-naphthamido) penicillin,1 is one of the semisynthetic, penicillinase-resistant penicillins that has been introduced since the isolation of 6-aminopenicillanic acid.2 Each of the newer penicillins in this series — namely, oxacillin, diphenicillin and nafcillin — has several readily apparent advantages over methicillin,3 the first one to become available for clinical use. Most important of these advantages are acid stability, permitting absorption of the drug when it is administered orally, and greater in vitro activity against both penicillinase-producing and nonpenicillinase-producing staphylococci. In addition, some data suggest that nafcillin may have greater therapeutic activity than methicillin or oxacillin in experimental infections in . . .

PRODUCTION OF 6-AMINOPENICILLANIC ACID BY DERMATOPHYTES.

FOLLOWING the isolation of 6-aminopenicillanic acid (6-APA) by Batchelor et al.1,2, a number of papers dealing with its formation both by fermentation and by microbial hydrolysis have been published3. Cole and Rolinson4 recently reported on production of 6-APA by certain species of Cephalosporium and Emericellopsis.

Aminoadipylpenicillin in penicillin fermentations.

THE isolation of 6-aminopenicillanic acid (6-APA)1 has led to renewed investigation into compounds of a penicillin-like nature found in penicillin fermentations. Wolff and Arnstein2 examined acetone extracts of mycelium and reported the presence of small amounts of unidentified phenylacetyl chloride-react ing substances in addition to 6-APA. No evidence was given, however, as to the nature of these substances. In the course of our own work we also examined extracts of the mycelium of Penicillium chrysogenum. 6-APA could be detected readily together with two hitherto unidentified penicillins, one of which is probably identical with the penicillin obtained recently by Flynn et al.3 and shown to be epimeric with cephalosporin N.

Methicillin treatment of severe staphylococcal disease. Observations in 146 cases.

UNTIL recently the antibiotic treatment of serious staphylococcal disease was hampered by the emergence of resistance of the organisms to most of the available antimicrobial agents and by the toxicity of those that remained effective. The nature of staphylococcal infections, their necrotizing character and their propensity to produce walled-off abscesses also tends to render the organisms difficult to reach by circulating antibacterial substances. The isolation of 6-aminopenicillanic acid by Batchelor et al.1 has made possible the production of semisynthetic penicillins that are resistant to staphylococcal penicillinase (or penicillinases) and are as nontoxic as penicillin G, thus offering hope of an . . .