How Are The Cephalosporins Synthesized Naturally

Clavulanic acid is isolated from Streptomyces clavuligerus [60-66], and sulbactam, a sulfone of penicillanic acid, is synthesized from 6-APA [67-69]. Both compounds have extremely weak antibacterial properties and act by forming irreversible complexes with beta-lactamase, which inactivates the enzyme, and as a result the beta-lactam antibiotic has time to destroy the microorganism. Currently, a number of combined drugs containing various combinations of beta-lactamase antibiotics and inhibitors are used.

32.1.2 Cephalosporins

A number of antibiotics (cephalosporins P, N, C) were isolated from the products of fermentation of the fungus Cephalosporium acremonicum. The major component of the mixture is cephalosporin C, an amide, the acid part of which is a-aminoadipic acid, and amine part—7-aminocephalosporanic acid.

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Cephalosporin C

Chemical or enzymatic hydrolysis of this compound allows to obtain large quantities of 7-aminocephalosporanic acid. A number of semisynthetic beta-lactam cephalosporin antibiotics were created by acylating the amino group of the last with various acid derivatives (analogous to the semisynthetic penicillin series) and currently there are about 25,000 of them, of which about 100 are used in medicine. Unlike penicillins, semisynthetic cephalosporins are synthesized not only by expanding the spectrum of various acids by which 7-aminocephalosporanic acid is acylated, but also by internal modifications of aminocephalosporanic nucleus (R1 and R2).

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7-aminocyepalosporanic acid Semisynthetic cephalosporins cooh cooh

7-aminocyepalosporanic acid Semisynthetic cephalosporins

The cephalosporin nucleus is synthesized with a beta-lactam ring attached to a six-membered dihydrothiazine ring. Unlike the penicillin nucleus, the cephalosporin nucleus is much more resistant to beta-lactamase. Moreover, it has large areas for possible modifications. Modifications in the acyl side chain alter the antibacterial activity, while modifications of R2 are associated with changes in the pharmacokinetics and metabolic parameters of the drug.

Radicals R: in the acyl side chain are basically the same or differ slightly from those used in penicillin synthesis.

At the same time, modifications of R2 are quite essential and can be determined as the following:

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  • Gundolpho
    How are the cephalosporins synthesized naturally?
    1 year ago

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