Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 40

Anti‐Infective Medicines/Antibacterials/Beta‐Lactam Medicines

Penicillins are produced by fermentation or are semisynthetic. A semisynthetic penicillin is often formed by acylation of the amine of 6‐aminopenicillanic acid (6‐APA). 6‐APA is produced from penicillin G (benzylpenicillin) by enzyme‐mediated hydrolysis of the side‐chain amide.

Discussion. Ampicillin is a semisynthetic penicillin. The final step is release of the amine by hydrolysis of an enamine. The side‐chain amide is formed by enzyme‐mediated formation of the reaction of 6‐aminopenicillanic acid (6‐APA) with a mixed anhydride. 6‐Aminopenicillanic acid is formed by enzyme‐mediated hydrolysis of the side‐chain amide of penicillin G. Penicillin G (benzylpenicillin) is produced by the fungus P. chrysogenum.

The mixed anhydride is formed from the potassium carboxylate salt and pivaloyl chloride. The N‐protected potassium carboxylate salt of the amino acid (known as a Dane Salt) is formed from (R)‐α‐phenylglycine and ethyl acetoacetate.