Antibacterial Natural Products in Medicinal Chemistry-Exodus or Revival?

To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti‐infectives. Surprisingly, numerous “old” classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the “old fashioned” natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target‐finding tools from biology (reversed genomics) is one option for their revival. Nature's universe of antibacterial compounds has evolved over millions of years and chemists have exploited this treasure of lead structures for half a century. The β‐lactams and the macrolides are outstanding success stories of this era. Today, natural products and basic antibacterial research seem to be “endangered species”. Revisiting natural products with modern chemistry and reversed genomics is one option for their revival.