Structure elucidation of prenyl- and geranyl substituted coumarins in <i>Gerbera piloselloides</i> by NMR spectroscopy, electronic circular dichroism calculations, and single crystal X-ray crystallography

Crude ethyl acetate extract of Gerbera piloselloides (L.) Cass. was investigated by dual high-resolution PTP1B/&alpha;-glucosidase inhibition profiling and LC-PDA-HRMS. This indicated the presence of a series of unprecedented prenyl- and geranyl-substituted coumarin derivatives correlated with both &alpha;-glucosidase and PTP1B inhibitory activity. Repeated chromatographic separation targeting these compounds led to the isolation of 13 new compounds, of which ten could be isolated as both enantiomers after chiral separation. The structures of all isolated compounds were characterized by HRMS and extensive 1D and 2D NMR analysis. The absolute configurations of the isolated compounds were determined by comparison of experimental and calculated electronic circular dichroism spectra. Compound 6 features a rare furan-oxepane 5/7 ring system, possibly formed through addition of a geranyl unit to C-3 of 5-methylcoumarin, representing a new type of geranyl-substituted coumarin skeleton. Compounds 19 and 24 are the first examples of dimeric natural products consisting of both coumarin and chromone moieties

Identification of α-glucosidase inhibitors in <i>Machilus litseifolia</i> by combined use of high-resolution α-glucosidase inhibition profiling and HPLC-PDA-HRMS-SPE-NMR

Type 2 diabetes is a chronic multifactorial disease affecting more than 425 million people worldwide, and new selective α-glucosidase inhibitors with fewer side effects are urgently needed. In this study, a crude ethyl acetate extract of Machilus litseifolia was fractionated by solid-phase extraction using C18 cartridges to give a fraction enriched in α-glucosidase inhibitors. Subsequent microfractionation and bioassaying of the eluate by high-performance liquid chromatography (HPLC) using a complementary pentafluorophenyl column allowed construction of a high-resolution α-glucosidase inhibition profile (biochromatogram). This was used to target high-performance liquid chromatography–photodiode array detection–high-resolution mass spectrometry–solid-phase extraction–nuclear magnetic resonance spectroscopy (HPLC-PDA-HRMS-SPE-NMR) analysis toward α-glucosidase inhibitors. This led to the identification of 13 dicoumaroylated flavonol rhamnosides, of which seven (8, 10, 12a, 12b, 16, 17, and 18) are reported for the first time, and two lignans, of which one (5) is reported for the first time. IC50 values of isolated compounds toward α-glucosidase range from 5.9 to 35.3 μM, which is 8 to 91 times lower than the IC50 value of 266 μM measured for the reference compound acarbose