FGF-1

Motivated by the significant bioactivities and therapeutic potential of 1,4-benzodioxan derivatives, we reported the asymmetric total synthesis of amovillosumins A (1) and B (2), two architecturally unique norlignans isolated from Amomum villosum. The target compounds were achieved in nine and seven steps, respectively, from commercially available materials, delivering exceptional overall yields (45-47 %) with excellent enantiopurity (91-95 % ee). The key synthesis strategies encompassed Williamson ether formation, stereocontrolled ketone reduction, and Ullmann coupling to establish the pivotal 1,4-dioxan scaffold. This synthetic approach unambiguously confirmed the absolute configurations of amovillosumins A and B while providing sufficient quantities for comprehensive biological evaluation. Biological studies demonstrated that (+)-7S,8S-1 significantly stimulated GLP-1 secretion by 344.4 % at 25 μM, obviously stronger than its enantiomer (-)-7R,8R-1 (149.5 %). All isomers displayed significant anti-inflammatory activity in LPS-stimulated Raw264.7 cells, and especially, (+)-R-2 and (-)-S-2 (IC₅₀ = 20.2 and 17.8 μΜ) showed six-fold greater NO inhibition than indometacin (IC₅₀ = 113.2 μM). Mechanistic study demonstrated that (-)-S-2 significantly suppressed the mRNA expression of both Inos and Ptgs2. Network pharmacological analysis further confirmed PTGS2 as the primary target mediating the anti-inflammatory effects of (-)-S-2. This study integrates synthetic chemistry with pharmacological evaluation, offering structural confirmation and therapeutic insights into amovillosumins A and B.