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

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 <italic>S</italic>‐adenosyl‐L‐methionine (SAM) methylation cofactor <italic>in situ</italic> 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 <italic>O</italic>‐methyltransferases <italic>Rn</italic>COMT, <italic>Mx</italic>SafC and <italic>Np</italic>N4OMT with high conversions and regioselectivities. In addition, the cascade was successfully trialled with the less toxic methyl group donor, methyl tosylate. [ABSTRACT FROM AUTHOR]