Design and Evolution of an Artificial Friedel-Crafts Alkylation Enzyme Featuring an Organoboronic Acid Residue.

ABSTRACT

Creating artificial enzymes by the genetic incorporation of noncanonical amino acids with catalytic side chains would expand the enzyme chemistries that have not been discovered in nature. Here, we report the design of an artificial enzyme that uses p-boronophenylalanine as the catalytic residue. The artificial enzyme catalyzes Michael-type Friedel-Crafts alkylation through covalent activation. The designer enzyme was further engineered to afford high yields with excellent enantioselectivities. We next developed a practical method for preparative-scale reactions by whole-cell catalysis. This enzymatic C-C bond formation reaction was combined with palladium-catalyzed dearomative arylation to achieve the efficient synthesis of spiroindolenine compounds.