Biocatalytic Halocyclization of Amides Enables By Vanadium Haloperoxidases

Marine algae are a rich source of bioactive halogenated natural products. Thepresence of these marine natural products has largely been attributed to their biosynthesis by organisms in these environments through a variety of different halogenation mechanisms. One of the key contributors in these halogenation processes are from the vanadium haloperoxidases (VHPOs) class of enzymes. VHPOs perform an electrophilic halogenation through the oxidation of halide ions with hydrogen peroxide as the terminal oxidant. This technique produces an electrophilic halide equivalent that can directly halogenate organic substrates. Despite the numerous known reaction capabilities of this enzyme class, their construction of intramolecular ring formation between a carbon and nitrogen atom has remained unreported. Herein, this study presents a development of a ‘new to nature’ chemical reaction for lactam synthesis. In pursuit of this type of reaction, it was discovered that wild type VHPOs (e.g., Curvularia inaequalis, Corallina officinalis, Corallina pilulifera, Acaryochloria marina) produce halogenated iminolactone compounds from acyclic amides in excellent yields and selectivity greater than 99 percent yield. The extension to chlorocyclizations will also be discussed.