Discovery and Syntheses of "Superbug Challengers"-Platensimycin and Platencin

Bacteria have developed resistance to almost all existing antibiotics known today and this has been a major issue over the last few decades. The search for a new class of antibiotics with a new mode of action to fight these multiply‐drug‐resistant strains, or “superbugs”, allowed a team of scientists at Merck to discover two novel antibiotics, platensimycin and platencin using advanced screening strategies, as inhibitors of bacterial fatty acid biosynthesis, which is essential for the survival of bacteria. Though both these antibiotics are structurally related, they work by slightly different mechanisms and target different enzymes conserved in the bacterial fatty acid biosynthesis. This Focus Review summarizes the synthetic and biological aspects of these natural products and their analogues and congeners. Averting a crisis: Discovery of the new class of antibiotics platensimycin and platencin that work with a novel mode of action is a turning point in antibiotic research. A comprehensive account on the demand for new antibiotics and the synthetic and biological aspects of platensimycin, platencin, and their analogues and congeners is provided in this Focus Review.