Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 60

Anti‐Infective Medicines/Antibacterials/β‐Lactam Medicines

A single‐enantiomer molecule with multiple chiral carbons is often formed by modification of a natural product which has most or all of the chiral carbons already in place.

Discussion. In the final step, the carboxylic acid of aztreonam is released by hydrolysis of the tert‐butyl ester. The amide bond near the center of the molecule is formed by reaction of the amine of the ammonium sulfamate zwitterion with a thioester.

The amine of the ammonium sulfamate zwitterion is released by cleavage of the protecting group. The β‐lactam ring is formed by displacement of the secondary methanesulfonate by the N‐acylsulfamate nitrogen. The N‐acyl sulfamate is formed from the amide. The methanesulfonate is formed from the alcohol. The amine of L‐threonine amide is protected (List the protecting groups. Select one protecting group to use in the analysis). L‐Threonine amide is formed from L‐threonine methyl ester. L‐Threonine methyl ester hydrochloride is formed from L‐threonine (Fischer Esterification). L‐Threonine is produced by fermentation.

The thioester is formed from the carboxylic acid and 2,2′‐dithiobis(benzothiazole). The carboxylic acid is formed by hydrolysis of the ethyl ester. The O‐alkyloxime is formed by O‐alkylation of the oxime with tert‐butyl α‐bromoisobutyrate. The thiazole ring is formed by reaction of an α‐bromoketone with thiourea (Hantzsch Thiazole Synthesis). The α‐bromoketone is formed by bromination of the ketone. The oxime is formed by nitrosation of ethyl acetoacetate.