Engineering Styrene Monooxygenases for Stereo-Complementary Synthesis of Furoindolines and Pyranoindolines via Asymmetric Oxidative Dearomatization of Indol-3-yl Alcohols

The efficient and direct asymmetric synthesis of O-heterocyclic [2,3]-fused indolines is a pivotal step in the total synthesis of numerous indole alkaloids, yet biocatalytic strategies remain underdeveloped. Herein, we report the development of tailor-made styrene monooxygenases to catalyze the stereo-complementary asymmetric dearomatization of indol-3-yl alcohols, allowing access to a diverse array of optically pure furoindolines and pyranoindolines. This establishes an efficient and broadly applicable enzymatic methodology for the synthesis of various alkaloids from indole precursors.