Nature Inspired Small Molecules for Chemical Biology

Abstract Chemical biology and drug discovery are instrumental sciences to address unmet medical needs and to gain a deeper understanding of normal and disease state biology in mammalian systems. Unlike most genetic tools, the small molecule modulation of biology is reversible, controllable in space, time and quantity, avoids the removal of gene products from cellular systems and thus enables perturbation of biology in its native state. Natural products, their derivatives as well as small molecules based on the core‐scaffolds of natural products including natural product fragments allow targeting unique, biologically relevant fractions of chemical space that may deliver quality tool compounds. In this essay, we discuss various synthesis approaches inspired by natural products to deliver biologically active small molecules. We argue and provide evidence that inspiration by natural product structure remains a powerful guiding principle for the development of novel approaches to the study biology by means of novel bioactive small molecules.