Alternative Reactivity of Leucine 5‑Hydroxylase Using an Olefin-Containing Substrate to Construct a Substituted Piperidine Ring

Applying enzymatic reactions to produce useful molecules is a central focus of chemical biology. Iron and 2-oxoglutarate (Fe/2OG) enzymes are found in all kingdoms of life and catalyze a broad array of oxidative transformations. Herein, we demonstrate that the activity of an Fe/2OG enzyme can be redirected when changing the targeted carbon hybridization from sp³ to sp². During leucine 5-hydroxylase catalysis, installation of an olefin group onto the substrate redirects the Fe­(IV)–oxo species reactivity from hydroxylation to asymmetric epoxidation. The resulting epoxide subsequently undergoes intramolecular cyclization to form the substituted piperidine, 2S,5S-hydroxypipecolic acid.