From natural product to marketed drug: the tiacumicin odyssey
The first members of the tiacumicin family of antibiotics, encompassing more than 40 compounds, were isolated in 1975. Structurally, the core aglycon is an 18-membered macrolactone having two conjugated diene units, one isolated double bond, 5 stereogenic centers and most often, at least one glycosidic linkage. Tiacumicin B, a RNA synthesis inhibitor, is a narrow-spectrum antibiotic against clostridia. For the treatment of Clostridium difficile infection (CDI), it has the same cure rate as vancomycin but with lower relapse rate and was approved by the FDA in May 2011. The aim of this review is to present an overview of the chemistry and biology of tiacumicins since their discovery.