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Tetracyclines: History, Nomenclature, Stereochemistry, SAR, Chemical Degradation

Historical Background:

  • The first tetracycline, chlortetracycline, was discovered in the late 1940s in a soil sample.

Nomenclature:

  • Tetracyclines are named for the presence of four ("tetra-") hydrocarbon rings in their structure.

Stereochemistry:

  • The tetracycline core structure has several chiral centers. Differences in these centers result in different tetracycline antibiotics.

Structure-Activity Relationship:

  • These are broad-spectrum antibiotics, named for their four-ring structure, that also work by inhibiting bacterial protein synthesis.

  • Their key structural elements include:

1.Four-Ring Structure:

  • The four-ring structure is important for the function of tetracyclines.

  • Changes to this structure can greatly affect their activity.

2.Functional Groups:

  • The functional groups attached to the tetracycline core are crucial for their antibacterial activity.

  • For example, the hydroxyl and dimethylamino groups at positions C-5 and C-4', respectively, are important for antibacterial activity, and modifications at these positions can result in decreased activity.

Chemical Degradation:

  • Tetracyclines can be degraded by epimerization and loss of the dimethylamino group


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