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

Here we report the development of a biomethylation cascade combining aspects of the MAT-MT-MTAN and MT-HMT cascades (Scheme 1b). Notably, the addition of MAT (with ATP and L-methionine) – and referred to as a ‘primed cascade’ to enable the initial in situ generation of SAM for use with the MT and then HMT and avoid the requirement for SAM/SAH. Furthermore, we report the application of this cascade with RnCOMT, MxSafC, and the norbelladine 4’-O-methyltransferase from Narcissus pseudonarcissus (NpN4OMT),[24] to give products with high regioselectivities.