Novel Skeleton Flavan-Alkaloids from African Herb Tea Kinkéliba: Isolation, Characterization, Semisynthesis, and Bioactivities

A series of novel skeleton flavan-alkaloids were discovered in the leaves of the African shrub kinkéliba (Combretum micranthum), which is one of the main traditional herbal teas of Senegal and is also used in foods and herbal medicine in West Africa. These flavan-alkaloids, named kinkéloids in honor of the plant, consist of two major parts including a flavan unit and an attached piperidine ring. Their structures were characterized using ultraviolet-visible spectroscopy, mass spectrometry (MS), and NMR. Kinkéloids in C. micranthum can be subdivided into four series - kinkéloids A, B, C, and D - differing from each other by the addition of one hydroxyl group. Each group of kinkéloids has two structural isomers with a piperidine ring attached at the 6 or 8 position of flavan, with two to three chiral centers. Kinkéloids A was artificially semisynthesized through three-step reactions, and its comparison with plant samples further confirmed the identities deduced from spectral analysis. The n-butanol fraction enriched in kinkéloids derived from crude extract was subjected to both in vitro and in vivo biological activity tests and showed potent inhibition of the messenger RNA expression of phosphoenolpyruvate carboxykinase in vitro on the H4IIE cell line and an increase of the glucose tolerance in vivo on the C57BL/6J mice model.