Tetracycline Amide Antibiotics

Tetracyclines are a group of broadband-spectrum antibiotics that comprise a distinct family of substituted hydronaphthacene compounds. This chapter discusses the history, synthesis, mode of action, and the structure-activity relationships of tetracycline amide antibiotics. Tetracyclines are divided into three generations. First generation tetracyclines include chlortetracycline, oxytetracycline, tetracycline, and demethylchlortetracycline. Examples of second generation tetracyclines are rolitetracycline, lymecycline, doxycycline, and minocycline. Tigecycline (10) is a third-generation tetracycline. In 1962, researchers succeeded in the first total synthesis of a biologically active tetracycline, (±)-6-demethyl-6-deoxytetracycline (22). Tetracyclines inhibit many enzyme reactions that are important for the vital processes of bacterial and mammalian cells. The most sensitive biochemical reaction that is inhibited by tetracyclines, however, is the biosynthesis of proteins. Analysis of the relationships between the molecular structures of tetracycline and the in vivo biological activities of these compounds shows that only little modifications to the tetracycline skeleton are tolerated for maintaining their biological activity.