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.