Evolution of Biocatalytic and Chemocatalytic C–H Functionalization Strategy in the Synthesis of Manzacidin C

Because of their unique molecular architecture, the manzacidins have been the subject of intense synthetic efforts in the past two decades. Here, we describe two synthetic approaches toward manzacidin C that center on the enzymatic hydroxylation of unprotected l-leucine. This study also resulted in the discovery of novel synthetic methodologies, including a photocatalytic C–H azidation of unprotected amino acids. Additionally, we describe the use of hydroxylated l-leucine in the preparation of various densely substituted pyrrolidines.