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Macrolides


Historical Background

  • First discovered in 1952 (Erythromycin from Saccharopolyspora erythraea).

  • Used for respiratory infections and atypical bacteria.

Nomenclature

  • Named after the macrocyclic lactone ring.

  • Examples:

    • Erythromycin

    • Clarithromycin

    • Azithromycin

Stereochemistry

  • 14-, 15-, or 16-membered lactone rings.

  • Various sugar moieties (e.g., desosamine, cladinose).

Structure-Activity Relationship (SAR)

  • Lactone ring size: Affects ribosomal binding.

  • Sugar modifications:

    • Improve acid stability (Clarithromycin, Azithromycin).

    • Enhance bioavailability.

  • C-9 modifications: Affect efflux pump resistance.

Chemical Degradation Classification

  • Acid instability: Leads to inactive ketal products (Erythromycin).

  • Hydrolysis of lactone ring.

  • Oxidative degradation.

Important Products

  • Erythromycin (first macrolide).

  • Clarithromycin (acid-stable, better absorption).

  • Azithromycin (long half-life, broad spectrum).

  • Roxithromycin (enhanced tissue penetration).


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