Asymmetric Alkene and Arene Halofunctionalization Reactions in Meroterpenoid Biosynthesis

Meroterpenoid natural products are important bioactive molecules with broad distribution throughout nature. In Streptomyces bacteria, naphthoquinone-based meroterpenoids comprise a simple yet structurally fascinating group of natural product antibiotics that are enzymatically constructed through a series of asymmetric alkene and arene halofunctionalization reactions. This account article highlights our discovery and characterization of a group of vanadium-dependent chloroperoxidase enzymes that catalyze halogen-assisted cyclization and rearrangement reactions and have inspired biomimetic syntheses of numerous meroterpenoid natural products. 1 Introduction 2 Early Biosynthetic Insights and the Characterization of Alkene Halofunctionalization in Napyradiomycin Biosynthesis 3 Discovery of the Merochlorin Natural Products and Enzymatic Aryl Halofunctionalization 4 Discovery and Development of Unifying THN-Based Meroterpenoid Biosynthesis and Synthesis Approaches 5 Insights into Naphterpin and Marinone Biosynthesis Involving Cryptic Aryl Halofunctionalization Reactions 6 Closing Thoughts