Synthesis of Enantiopure Unnatural Amino Acids by Metallaphotoredox Catalysis

We describe herein a two-step process for the conversion of serine to a wide array of optically pure unnatural amino acids. This method utilizes a photocatalytic cross-electrophile coupling between a bromoalkyl intermediate and a diverse set of aryl halides to produce artificial analogues of phenylalanine, tryptophan, and histidine. The reaction is tolerant of a broad range of functionalities and can be leveraged toward the scalable synthesis of valuable pharmaceutical scaffolds via flow technology.

Automated summary

The conversion of serine to optically pure unnatural amino acids can be achieved through a two-step process utilizing a photocatalytic cross-electrophile coupling. This method produces artificial analogues of phenylalanine, tryptophan, and histidine, and is tolerant of a broad range of functionalities. It can also be leveraged for the scalable synthesis of valuable pharmaceutical scaffolds via flow technology.