An Alternative Cascade for the Selective Methylation of Catechols and Tetrahydroisoquinolines by O-Methyltransferases

Abstract

Methyltransferases are gaining traction as a method to achieve greener and regioselective methylations of a wide array of substrates. In this work, a halide methyltransferase biomethylation cascade was successfully adapted with the incorporation of a methionine adenosyltransferase to generate the S-adenosyl-L-methionine (SAM) methylation cofactor in situ from less costly ATP and L-methionine, instead of directly adding SAM to start the cascade. Furthermore, this cascade was applied to achieve novel catechol and tetrahydroisoquinoline methylations with the O-methyltransferases RnCOMT, MxSafC and NpN4OMT with high conversions and regioselectivities. In addition, the cascade was successfully trialled with the less toxic methyl group donor, methyl tosylate.