Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly straine...Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly strained and bridged eight-membered carbocycle of predysidavarone 6 was constructed by a one-pot intermolecular alkylation and intramolecular arylation of Wieland–Miescher ketone derivative 11 and benzyl bromide 12.The total synthesis of(+)-dysidavarones A–C(1–3)was achieved from predysidavarone 6 in a divergent manner by a late-stage introduction of the ethoxy group,which reveals the possible source of the ethoxy group within(+)-dysidavarones A–C(1–3)and provides a late-stage modifiable route for the synthesis of dysidavarone analogs for further anti-cancer activity evaluation.展开更多
Three phthalide-derived analogues,oxaspiroangelioic acids A–C(1–3),were isolated as minor components of an aqueous extract of the Angelica sinensis root heads(guitou).Oxaspiroangelioic acids A and B were racemates s...Three phthalide-derived analogues,oxaspiroangelioic acids A–C(1–3),were isolated as minor components of an aqueous extract of the Angelica sinensis root heads(guitou).Oxaspiroangelioic acids A and B were racemates separated into enantiomers by chiral HPLC.Their structures including absolute configurations were determined by spectroscopic data analysis,single crystal X-ray diffraction,exciton chirality method [7_(T)D$IF]and electronic circular dichroism(ECD) calculation.These compounds share an undescribed carbon skeleton,for which biosynthetic pathways are proposed.Compound 1 and its enantiomers showed almost identical activity inhibiting Tandem of P domains in a weak inwardly rectifying K^(+)channel 1(TREK-1).展开更多
Three new napelline-type C20-diterpenoid alkaloids,named aconicarmichinium A and B trifluoroacetates(1 and 2) and aconicarmichinium C chloride(3),were isolated from an aqueous extract of "fu zi",the lateral root...Three new napelline-type C20-diterpenoid alkaloids,named aconicarmichinium A and B trifluoroacetates(1 and 2) and aconicarmichinium C chloride(3),were isolated from an aqueous extract of "fu zi",the lateral roots of Aconitum carmichaelii.Their structures were elucidated by extensive spectroscopic data analysis.Compounds 1-3 represent the first examples of napelline-type C20 diterpenoid alkaloid alcohol iminiums,of which the structures were fully characterized.In addition,transformation and equilibration between the alcohol iminiums(1-3) and the aza acetals la-3a were investigated by measurements of the NMR spectra in protic and aprotic deuterium solvents including alkali pyridine-d5,along with evaporation under reduced pressure and gradual additions of TFA,AcOH,and HC1.The results demonstrated that the transformation and equilibration were solvent-,base-,and acid-dependent.Especially,in aqueous biological fluid,these C20-diterpenoid alkaloids would more likely exist as the alcohol iminiums accompanied by anion counterparts in biosystems to increase their solubility, bioavailability, transportations, and functions.The absolute configurations of 1-3 were confirmed by X-ray crystallographic analysis of 2a.展开更多
Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathog...Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis,has been extensively applied in evaluating the course of diseases.In this study,we used this approach to analyse the abundance of metabolites,with liquid chromatograph-mass spectrometer,in plasma samples from rats with transverse aortic constriction(TAC) and patients at different stages of HF.We compared the metabolic parameters within and between TAC rats and patients.An apparent metabolic shift was observed in rats,from compensated hypertrophy stage to decompensated hypertrophy stage,and in patients with HF,from stage A to stage B and subsequently stage C.Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients.Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways,and those interfered at different stages and across species were confirmed.The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis,hinted at novel potential biomarkers,and provided potential therapeutic intervention targets for HF.展开更多
Three new lignan glucosides, baicalensinosides A–C(1–3), were isolated from the roots of Scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemic...Three new lignan glucosides, baicalensinosides A–C(1–3), were isolated from the roots of Scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemical test. Structurally, these compounds belong to the 3,4-dibenzyltetrahydrofurantype lignan glycoside with a mono-hydroxyl substitution at the 70-position of benzylidene group on the numbering system of lignans being one of their shared critical features. The anti-osteoporotic activity of the isolated compounds was assessed in an in vitro osteoprotegerin(OPG) transcriptional activity assay using dual luciferase reporter detection. At 10 μmol/L, compounds 1–3 increased the relative activating ratio of OPG transcription to 1.83, 0.84 and 0.98 times that of the control group, respectively.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.22171146,21971121,and 22188101 to ZL)the China Postdoctoral Science Foundation(No.2021M701775 to CC)。
文摘Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly strained and bridged eight-membered carbocycle of predysidavarone 6 was constructed by a one-pot intermolecular alkylation and intramolecular arylation of Wieland–Miescher ketone derivative 11 and benzyl bromide 12.The total synthesis of(+)-dysidavarones A–C(1–3)was achieved from predysidavarone 6 in a divergent manner by a late-stage introduction of the ethoxy group,which reveals the possible source of the ethoxy group within(+)-dysidavarones A–C(1–3)and provides a late-stage modifiable route for the synthesis of dysidavarone analogs for further anti-cancer activity evaluation.
基金Financial support from the National Natural Sciences Foundation of China (No.81630094)CAMS Innovation Fund for Medical Science (No.2017-I2M-3-010, China)The Drug Innovation Major Project (Nos.2018ZX09711001-004 and 2018ZX09711001-001, China)。
文摘Three phthalide-derived analogues,oxaspiroangelioic acids A–C(1–3),were isolated as minor components of an aqueous extract of the Angelica sinensis root heads(guitou).Oxaspiroangelioic acids A and B were racemates separated into enantiomers by chiral HPLC.Their structures including absolute configurations were determined by spectroscopic data analysis,single crystal X-ray diffraction,exciton chirality method [7_(T)D$IF]and electronic circular dichroism(ECD) calculation.These compounds share an undescribed carbon skeleton,for which biosynthetic pathways are proposed.Compound 1 and its enantiomers showed almost identical activity inhibiting Tandem of P domains in a weak inwardly rectifying K^(+)channel 1(TREK-1).
基金Financial support from the National Natural Science Foundation of China (NNSFC Nos. 21132009, 30825044)the National Science and Technology Project of China (Nos. 2012ZX09301002002, 2011ZX0 9307-002-01)
文摘Three new napelline-type C20-diterpenoid alkaloids,named aconicarmichinium A and B trifluoroacetates(1 and 2) and aconicarmichinium C chloride(3),were isolated from an aqueous extract of "fu zi",the lateral roots of Aconitum carmichaelii.Their structures were elucidated by extensive spectroscopic data analysis.Compounds 1-3 represent the first examples of napelline-type C20 diterpenoid alkaloid alcohol iminiums,of which the structures were fully characterized.In addition,transformation and equilibration between the alcohol iminiums(1-3) and the aza acetals la-3a were investigated by measurements of the NMR spectra in protic and aprotic deuterium solvents including alkali pyridine-d5,along with evaporation under reduced pressure and gradual additions of TFA,AcOH,and HC1.The results demonstrated that the transformation and equilibration were solvent-,base-,and acid-dependent.Especially,in aqueous biological fluid,these C20-diterpenoid alkaloids would more likely exist as the alcohol iminiums accompanied by anion counterparts in biosystems to increase their solubility, bioavailability, transportations, and functions.The absolute configurations of 1-3 were confirmed by X-ray crystallographic analysis of 2a.
基金supported by the National Natural Science Foundation of China (81625001, 81700010)National Key Research & Development Program of China (2018YFC1312700, 2018YFC1312701)
文摘Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis,has been extensively applied in evaluating the course of diseases.In this study,we used this approach to analyse the abundance of metabolites,with liquid chromatograph-mass spectrometer,in plasma samples from rats with transverse aortic constriction(TAC) and patients at different stages of HF.We compared the metabolic parameters within and between TAC rats and patients.An apparent metabolic shift was observed in rats,from compensated hypertrophy stage to decompensated hypertrophy stage,and in patients with HF,from stage A to stage B and subsequently stage C.Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients.Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways,and those interfered at different stages and across species were confirmed.The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis,hinted at novel potential biomarkers,and provided potential therapeutic intervention targets for HF.
基金supported by grants from National Natural Science Foundation of China(No.81361138020)
文摘Three new lignan glucosides, baicalensinosides A–C(1–3), were isolated from the roots of Scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemical test. Structurally, these compounds belong to the 3,4-dibenzyltetrahydrofurantype lignan glycoside with a mono-hydroxyl substitution at the 70-position of benzylidene group on the numbering system of lignans being one of their shared critical features. The anti-osteoporotic activity of the isolated compounds was assessed in an in vitro osteoprotegerin(OPG) transcriptional activity assay using dual luciferase reporter detection. At 10 μmol/L, compounds 1–3 increased the relative activating ratio of OPG transcription to 1.83, 0.84 and 0.98 times that of the control group, respectively.