Diarylheptanoids from Rhizomes of Alpinia officinarum Inhibit Aggregation of α‑Synuclein

Two new diarylheptanoids, alpinin A (<b>1</b>) and alpinin B (<b>2</b>), together with 18 known diarylheptanoids (<b>3</b>–<b>20</b>), were isolated from the rhizomes of Alpinia officinarum. Their structures were elucidated by comprehensive spectroscopic analysis, including high-resolution mass spectrometry, infrared spectroscopy, and one- and two-dimensional nuclear magnetic resonance spectroscopy. Structurally, alpinin A is a new member of the small family of oxa-bridged diarylheptanoids and contains the characteristic 2,6-<i>cis</i>-configured tetrahydropyran motif (C₁–C₅ oxa bridge). The absolute configuration of alpinin A was confirmed by asymmetric total synthesis of the enantiomer (<i>ent</i>-<b>1</b>), corroborating the assignment of the molecular structure. The absolute configuration of alpinin B was determined on the basis of the analysis of the circular dichroism exciton chirality spectrum. We evaluated the inhibitory activity of all isolated diarylheptanoids against α-synuclein aggregation at 10 μM. Alpinins A and B significantly inhibited α-synuclein aggregation by 66 and 67%, respectively