α‑Glucosidase Inhibitors from the Stems of Knema globularia

Six new compounds, globunones A–F (1–6), and two new flavonoids (7 and 8) together with nine known compounds (9–17) were isolated from the stems of Knema globularia. The chemical structures of 1–8 were elucidated by an analysis of their NMR and high-resolution electrospray ionization mass spectrometry data as well as by comparison with literature values. The absolute configurations were determined using time-dependent density functional theory electronic circular dichroism (TD-DFT-ECD). Globunones A–E (1–5) represent the initial combined structures of a flavan-3-ol core and a 1,4-benzoquinone core. Globunone F (6) is the first flavanone-type compound bearing a 2-(2,4-dihydroxyphenyl)-2-oxoethyl group found to date in Nature. Compounds 1–3 and 6–17 were tested for their yeast α-glucosidase inhibitory activity. All compounds tested (except for 13 and 14) showed potent inhibition toward α-glucosidase with IC50 values in the range 0.4–26.6 μM. Calodenin A (15) was the most active compound with an IC50 value of 0.4 μM (the positive control, acarbose, IC50 93.6 μM). A kinetic analysis of 15 revealed that it is a noncompetitive inhibitor with a K i value of 3.4 μM.