Dual High-Resolution α-Glucosidase and PTP1B Inhibition Profiling Combined with HPLC-PDA-HRMS-SPE-NMR Analysis for the Identification of Potentially Antidiabetic Chromene Meroterpenoids from Rhododendron capitatum

Thirteen previously undescribed chromene meroterpenoids, capitachromenic acids A-M ( 3 - 6 , 7a , 7b , 8a , 8b , 9a , 9b , 10a , 10b , and 11b ), were identified from an ethyl acetate extract of Rhododendron capitatum, using dual high-resolution α-glucosidase and PTP1B inhibition profiling in combination with HPLC-PDA-HRMS-SPE-NMR. In addition, one known chromene meroterpenoid daurichromenic acid ( 15 ) and its biosynthetic precursor, grifolic acid ( 12 ), two C-methylated flavanones, (2S)-5,7,4'-trihydroxy-8-methylflavanone ( 1 ) and farrerol ( 2 ), and two triterpenoids, oleanolic acid ( 14a ) and ursolic acid ( 14b ) were identified. New structures were elucidated by extensive 1D and 2D NMR analysis, and absolute configurations of new chromene meroterpenoids were assigned by analysis of their ECD spectra on the basis of the empirical chromane/chromene helicity rule and from Rh2(OCOCF3)4-induced ECD spectra by applying the bulkiness rule. Compounds 5 , 9a , 9b , 12 , and 15 showed α-glucosidase inhibitory activity with IC50 values ranging from 8.0 to 93.5 μM, while compounds 3 , 5 , 8b , 9a , 9b , 10b , 11b , 12 , and 15 showed PTP1B inhibitory activity with IC50 values ranging from 2.5 to 68.1 μM.