Chemoselective tagging to promote natural product discovery

Natural products are privileged scaffolds in the realm of drug discovery. The development and utilization of chemoselective probes in conjunction with mass spectrometry to identify new natural product leads have great potential to simplify and accelerate discovery. This chapter reviews recent advances, split broadly into two groups: nonreversible and reversible chemoselective probes. Building on the wealth of research in chemoselective probes for protein labeling, the development of covalent labels that are useful for natural product discovery has gained interest in the past decade. Comparative analysis of natural product libraries versus synthetic compound libraries indicates that their inherent biological functions and physicochemical properties make secondary metabolites privileged compounds in the drug discovery realm. Traditionally, natural products were isolated by exploiting properties such as size, charge, solubility, and hydrophobicity. Alkyne-containing natural products are produced across the biological kingdom and have a broad range of bioactivities.