Total Syntheses and Structural Reassignment of Ugonin T and Neougonin B: Anti-inflammatory Flavonoids Related to Helminthostachys zeylanica

This study reports the first total syntheses of the naturally occurring flavonoids ugonin C (1), ugonin F (2), and, based on the originally proposed structures, compounds 3 and 4 (corresponding to the structures first assigned to ugonin T and neougonin B, respectively), all featuring a dihydrofuran ring fused to a phenolic moiety. In addition, a series of analogues (18, 19, 22, 23a, 23b, 27a, 27b, and 28) were synthesized to explore their biological activities. On the basis of synthetic strategy and detailed NMR analyses, the structures of naturally occurring ugonin T and neougonin B were reassigned to correspond to compounds 23a and 19, respectively. Biological evaluation revealed that several synthesized compounds exhibited potent anti-inflammatory activity, particularly compound 27a, which showed the strongest inhibition of NF-κB associated nitric oxide production in BV2 microglial cells.