The Tetracyclines

1 Historical Introduction.- References.- 2 Fermentation and Mutational Development of the Tetracyclines.- A. Introduction.- B. The Producing Microorganisms.- C. The Fermentation Process.- D. Fermentation Technology.- E. Concluding Remarks.- References.- 3 Structure Determination and Total Synthesis of the Tetracyclines.- A. Introduction.- B. Structure Determination.- C. Partial Synthesis from Derivatives.- D. Total Synthesis of Tetracycline Derivatives and Incomplete Syntheses.- E. Total Synthesis of 6-Demethyl-6-deoxytetracycline.- F. Total Synthesis of Fermentation Tetracyclines.- G. Total Synthesis of Tetracycline Analogues.- References.- 4 Biosynthesis of the Tetracyclines.- A. Introduction.- B. Production Strains.- C. Building Units of Tetracyclines.- D. The Biosynthetic Pathway of Tetracyclines.- E. Regulation of the Biosynthesis of Tetracyclines.- E. Regulation of the Biosynthesis of Tetracyclines.- F. Biosynthesis of Macromolecules and the Production of Tetracyclines.- G. Conclusion.- References.- 5 Chemical Modification of the Tetracyclines.- A. Introduction.- B. Semisynthetic Tetracyclines.- C. Totally Synthetic Unnatural Tetracyclines.- D. Overall Structure-Activity Relationships.- References.- 6 Mode of Action of the Tetracyclines and the Nature of Bacterial Resistance to Them.- A. Introduction.- B. Mode of Action of the Tetracyclines: Studies Before 1964.- C. Current Views on the Nature of Bacterial Protein Synthesis.- D. Effects of Tetracyclines on Protein Synthesis in Prokaryotes.- E. Binding of Tetracyclines to Macromolecules.- F. Molecular Basis of Tetracycline Action.- G. Relation Between Structure and Activity in the Tetracyclines.- H. Effects of Growth in the Presence of Low Tetracycline Concentrations on Microbial Metabolism.- I. Selective Toxicityof the Tetracyclines.- J. Transport of Tetracyclines into Bacteria.- K. Plasmid-Determined Resistance to the Tetracyclines.- L. Chromosomal Mutation to Tetracycline Resistance.- M. Conclusions.- References.- 7 Clinical Uses of the Tetracyclines.- A. Antimicrobial Activity.- B. Clinical Uses.- C. Treatment of First Choice.- D. Effective Alternative Treatment.- E. Treatment of Clinical Syndromes.- F. Ineffective Treatment.- G. Dosage and Duration of Therapy.- References.- 8 Nonmedical Uses of the Tetracyclines.- A. Historical.- B. Growth Promotion and Improved Feed Efficiency in Livestock.- C. Disease Prevention Effects of Chlortetracycline and Oxytetracycline.- D. Public Health Considerations.- E. Government Restrictions.- References.