Total Synthesis and Anti-Inflammatory Activity of Tectoridin and Related Isoflavone Glucosides.

The first total syntheses of four isoflavone glucosides, tectoridin (1), tectoridin A (2), tectorigenin 7-O-β-d-glucopyranosyl-12-O-β-d-glucopyranoside (3), and isotectroigenin 7-O-β-d-glucopyranoside (4), have been accomplished. Key steps in our synthetic approach include a regioselective halogenation reaction, followed by methanolysis to introduce the -OCH3 group into isoflavone frameworks and a PTC-promoted stereoselective glycosidation to establish glycosidic bonds. The synthesized isoflavone glucosides (1-4) and their corresponding aglycones (32 and 34) were evaluated for anti-inflammatory activity against nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1 β (IL-1β) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Aglycones 32 and 34 exhibited stronger anti-inflammatory activity in vitro compared to isoflavone glucosides 1-4.