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

[Graphics] 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.