Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 58

Anti‐Infective Medicines/Antibacterials/Other Antibacterials

Ophthalmological Medicines/Anti‐Infective Agents

Macrolide antibiotics are produced by fermentation or are semisynthetic. The process for manufacture of a semisynthetic macrolide antibiotic often begins with conversion of the C9 ketone of erythromycin A to the oxime.

Discussion. Azithromycin is semisynthetic. Azithromycin is formed from the essential medicine erythromycin A which is produced by fermentation.

The tertiary amine of azithromycin is formed in the final step by methylation of the secondary amine with formaldehyde and formic acid (Eschweiler–Clarke Reaction). The secondary amine (9‐deoxo‐9a‐aza‐homoerythromycin) is formed by reduction of an iminoether. The 6,9‐iminoether (the iminoether involving the hydroxyl group at C6 and carbon at C9) is formed by rearrangement of an (E)‐O‐arylsulfonyl oxime (Beckmann Rearrangement). The (E)‐O‐arylsulfonyloxime is formed from the (E)‐oxime and an arylsulfonyl chloride (List the arylsulfonyl chlorides and (O)‐arylsulfonyloxime yields). (E)‐Erythromycin A oxime is formed from erythromycin A. (How is (E)‐erythromycin A oxime separated from (Z)‐erythromycin A oxime?)