Chemical Constituents From Atractylodes Lancea And Their Biological Activities

Atractylodes lancea is a kind of traditional Chinese medicine and commonly used to treat nyctalopia,stomachache,influenza,and other diseases.To further investigate its effective components,different crude extracts were screened under the guidance of in vitro bioactivities and UV spectra.Then,126 compounds were isolated from the n-BuOH part of an aq.EtOH extract of A.lancea using various column chromatographic methods.Their structures including absolute configurations were established on the basis of extensive spectroscopic data(UV,IR,1D and 2D NMR,HRESIMS,ECD,and X-ray).The identified structures contained 74 new and 52 known compounds.In particular,these new compounds were composed of eight spirovetivane-type sesquiterpenoids(1-8),ten eudesmane-type sesquiterpenoids(9-18).three guaiane-type sesquiterpenoids(19-21),two eremophilane-type sesquiterpenoids(22-23),eleven C10-linear polyacetylenes(24-34),twenty-one C13-linear polyacetylenes(35-55),six C,4-linear polyacetylenes(56-61).two C,3-furan polyacetylenes(62,63),five thiophene polyacetylenes(64-68),two furofuran-type lignans(69,70),two phenolic glycosides(71,72),one pyrazine derivative(73),and one prenylated dihydrobenzofuran derivative(74).The other known compounds(75-126)are mainly composed of sesquiterpenoids.polyacetylenes,lignans,coumarins,and so on.Based on the extensive chemical investigations,the biological effects of 85 compounds were evaluated.Compounds 2,4.22,24,27,71.72.73.84,109,and 122 showed potent hepatoprotective activities against N-acetyl-p-aminophenol-induced HepG2 cell injury at 10 μM,compared with the model groups.Compounds 3,4,9,47,90,120,122,and 123 showed potent anti-inflammatory effects on LPS-induced NO production of microglia BV2 cells at 10 μM.In the course of this subject research,a convenient and reliable NMR approach for discriminating the threo and erythro configurations of the acyclic vicinal diol groups in polyacetylene glycosides was developed.Using acetic acid-d4/D2O as the solvent,a relatively larger 3JHH value(7.0 Hz)was assigned to the threo configuration,whereas a smaller value(3.5 Hz)was assigned to the erythro configuration.The proportions of acetic acid-d4 can be adjusted slightly based on the solubility of the samples to be tested.This convenient NMR approach,in combination with other spectral data such as ECD,facilitates determination of the absolute configurations of polyacetylene glycosides and greatly diminishes the associated labor.In addition,an interesting phenomenon was observed in the course of determining the absolution configurations of compounds 1-5.Compounds 3-5,the aglycone of which possesses two stereogenic centers(C-5 and C-7),exhibited similar ECD spectra as compounds 1 and 2,the aglycone of which possesses one stereogenic center(C-7).Such a difference was further investigated by the experimental and calculated ECD data and single-crystallographic analyses of 3a.Comparison of the calculated ECD data of 3a with la revealed that the low-amplitude positive Cotton effect at approximately 275 nm is contributed by the cyclohexadienone moiety,while the high-amplitude positive Cotton effect approximately at 235 nm is derived from both the five-membered spirocycle and the cyclohexadienone units.Obviously,the positive Cotton effects at approximately 250 nm in the experimental ECD spectra of 3-5 may be the additive contribution of the respective chromophores.The information involved in this thesis will benefit subsequent stereochemical studies of spirovetivane-type sesquiterpenoids.