Formation of 1,3-Dihydroxy-N-methylacridone from N-Methylanthraniloyl-CoA and Malonyl-CoA by Cell-Free Extracts of Ruta graveolens

Cell-free extracts of Ruta graveolens cell sus­ pension cultures catalyze the condensation of N-methylanthranilic acid and malonyl-CoA in the presence of ATP and Mg2+ [1,2]. After addition of CoA-SH to the incubation mixture an inhibitory effect on alkaloid formation was observed as was previously described for the chalcone synthase reaction [3, 4]. It may be assumed that the incorpo­ ration of N-methylanthranilic acid proceeds via the corresponding CoA thiol ester. Activation of N-methylanthranilic acid in the presence of hydroxylamine was described earlier but the exact mechanism of this reaction has not been clarified e.g. a specific N-methylanthranilate: CoA ligase was not detected [5]. In this communication we report for the first time a chemical synthesis of N-methylanthraniloylCoA (1) and its role as primer molecule for the formation of 1,3-dihydroxy-N-methylacridone.