Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 38

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. Amoxicillin is a semisynthetic penicillin. The final step is enzyme‐mediated formation of the side‐chain amide by reaction of an amine with an ester. The amine, 6‐aminopenicillanic acid (6‐APA), is formed by enzyme‐mediated hydrolysis of the side‐chain amide of penicillin G. Penicillin G (benzylpenicillin) is produced by the fungus Penicillium chrysogenum.

The ester is formed from the carboxylic acid (Fischer Esterification). The α‐amino acid, (R)‐α‐(4‐hydroxyphenyl)glycine, is formed by enzyme‐mediated hydrolysis of the N‐carbamoyl α‐amino acid. The (R)‐N‐carbamoyl α‐amino acid is formed by enzyme‐mediated hydrolysis of the (R)‐hydantoin in a mixture of the (R)‐ and (S)‐hydantoins. Since the (R)‐ and (S)‐hydantoins interconvert under the hydrolysis conditions, the (S)‐hydantoin is also converted to the (R)‐N‐carbamoyl α‐amino acid. The mixture of (R)‐ and (S)‐hydantoins is formed from phenol, glyoxylic acid, and urea.