Biocatalyzed Cross-Coupling of Sinomenine and Guaiacol by <i>Antrodiella semisupina</i>

In search of more potent derivatives of sinomenine (1), a clinically available natural alkaloid for the treatment of rheumatoid arthritis (RA), biocatalyzed cross-coupling of sinomenine and guaiacol (2) by Antrodiella semisupina, provided two unique C−C coupled (3 and 4) and one C−O linked (5) novel metabolites. The structures of the metabolites were elucidated by means of MS, 2D NMR techniques and X-ray analysis. 4 exhibited more potent inhibitory activity on IL-6 production than 1 in human synovial sarcoma cell (SW982), and 5 stimulated IL-6 production.