Structure Revision of Lyciumamides A-C and Their Hypoglycemic Activities

Lyciumamides A-C (1a-3a) are three phenolamide dimers (neolignanamides) with unusual linkage types from the fruits of Lycium barbarum reported by Gao et al.[GaoK., ; MaD., ; ChengY., ; TianX., ; LuY., ; DuX., ; TangH., ; ChenJ., Three new dimers and two monomers of phenolic amides from the fruits of Lycium barbarum and their antioxidant activities. J. Agric. Food Chem.2015, 63, 1067-1075. 10.1021/jf5049222.]. Recently, Zadelhoff et al.[van ZadelhoffA., ; de BruijnW. J. C., ; VinckenJ.-P., Comment on "three new dimers and two monomers of phenolic amides from the fruits of Lycium barbarum and their antioxidant activities". J. Agric. Food Chem.2024. 72. 6781-6786. 10.1021/acs.jafc.3c08738.] suggested more reasonable structures with common linkage types for lyciumamides A-C, identifying them as the known compounds cannabisin F (1), grossamide (2), and grossamide K (3), respectively, by comparing the NMR data in the literature. However, the NMR data discussed by Zadelhoff et al. were insufficient to support the corrected structures, and the relative configurations of 2 and 3 were not assigned. In this report, we revised the structures of lyciumamides A-C as cannabisin F (1), grossamide (2b), and grossamide K (3b), respectively, with 1D and 2D NMR experiments and ¹³C NMR calculations. The absolute configurations of 2b and 3b were also assigned by comparing the experimental and calculated ECD spectra. Compound 3b was shown to promote preadipocyte differentiation and exhibit agonistic activity for peroxisome proliferator-activated receptor in adipocytes.