As a part of the ongoing search for new constituents of Stemona species in China, chemical investigation of Stemona sessilifolia, a plant used in the traditional Chinese medicine to treat respiratory disorders, was ca...As a part of the ongoing search for new constituents of Stemona species in China, chemical investigation of Stemona sessilifolia, a plant used in the traditional Chinese medicine to treat respiratory disorders, was carried out. To identify the chemical components rapidly, a selected sample of S. sessilifolia containing bibenzyls was tested using LC-ESIMS and analyzed further using stop-flow LC-UV-NMR, which was sensitive for the detection of the main constituents. LC microfractions were collected using the LC-UV-NMR technique and HR-EIMS off-line analysis was cartied out on the collected fractions. This chemical screening strategy allowed for the on-line identification of the main constituents of S. sessilifolia and provided information that was useful for a further peak-guided isolation procedure. Using these methods, four bibenzyls were isolated: two known compounds, 3,5-dihydroxy-4-methyl bibenzyl(1) and 3, 5-dihydroxy-2'-methoxy-4-methyl bibenzyl ( 2 ), and two novel compounds, 3,3'-dihydroxy-5, 6'-dimethoxy bibenzyl(3) and 3,5-dihydroxy-2', 5'-dimethoxy bibenzyl (4).展开更多
Bibenzyls,a kind of important plant polyphenols,have attracted growing attention for their broad and remarkable pharmacological activities.However,due to the low abundance in nature,uncontrollable and environmentally ...Bibenzyls,a kind of important plant polyphenols,have attracted growing attention for their broad and remarkable pharmacological activities.However,due to the low abundance in nature,uncontrollable and environmentally unfriendly chemical synthesis processes,these compounds are not readily accessible.Herein,one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes.Three types of efficiently postmodifying modular strains were engineered by employing methyltransferases,prenyltransferase,and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules.Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes.Especially,a prenylated bibenzyl derivative(12)was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke.RNA-seq,quantitative RT-PCR,and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor,mitochondria associated 3(Aifm3),suggesting that Aifm3 might be a new target in ischemic stroke therapy.This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.展开更多
The Ramberg-Bcklund rearrangement has been successfully utilized to convert readily available - and -hydrogen bearing substituted dibenzyl sulfones into corresponding stilbene derivatives, which is conveniently follow...The Ramberg-Bcklund rearrangement has been successfully utilized to convert readily available - and -hydrogen bearing substituted dibenzyl sulfones into corresponding stilbene derivatives, which is conveniently followed by hydrogenation in the presence of 10% Pd/C to afford the natural bibenzyls.展开更多
A new bibenzyl derivative, 3,4-dihydroxy-4,5-dimethoxy bibenzyl, was isolated from a orchid Dendrobium moniliforme. The structure elucidation and 1H,13C NMR assignments were achieved by spectroscopic method.
A new bibenzyl derivative 1, named 2-(4''-hydroxybenzy1)-3-(3'-hydroxyphenethy1)-5-methoxy-cyclohexa-2,5-diene-1,4- dione, and two known stilbenoids (2, 3) were isolated from the tubers of Pleione bulbocodioi...A new bibenzyl derivative 1, named 2-(4''-hydroxybenzy1)-3-(3'-hydroxyphenethy1)-5-methoxy-cyclohexa-2,5-diene-1,4- dione, and two known stilbenoids (2, 3) were isolated from the tubers of Pleione bulbocodioides (Franch.) Rolfe. Their structures were elucidated by spectroscopic methods.展开更多
15 compounds,including two new ones crepidatuols A(1)and B(2)were isolated from the stems of Dendrobium crepidatum.The planar structures of these compounds were elucidated by spectroscopic methods(NMR,MS,UV,and IR)and...15 compounds,including two new ones crepidatuols A(1)and B(2)were isolated from the stems of Dendrobium crepidatum.The planar structures of these compounds were elucidated by spectroscopic methods(NMR,MS,UV,and IR)and comparison with those from literatures.10 compounds were send for enhancing activities on nerve growth factor(NGF)medicated neurite outgrowth in PC12 cells and the results indicated that crepidatuol A(1),confusarin and 3-(2-acetoxy-5-methoxy)-phenylpropanol showed enhancing activities at the concentration of 10.0μM.展开更多
A new bibenzyl glycoside has been isolated from the stems of Dendrobium moniliforme (L.) Sw. (Orchidaceae). Its structure has been identified on the basis of spectroscopic and chemical methods.
Dendrobium officinale is a valuable medicinal herb that is widely used in traditional Chinese medicine.The chemical constituents of D.officinale have attracted much attention and a large number of compounds have been ...Dendrobium officinale is a valuable medicinal herb that is widely used in traditional Chinese medicine.The chemical constituents of D.officinale have attracted much attention and a large number of compounds have been reported including many bibenzyl derivatives.13 bibenzyl derivatives from D.officinale were sent for molecular docking,sur-face plasmon resonance(SPR)assay and after detection of Mn-SOD and SIRT3 activities in or not in HaCaT cells,it was concluded that bibenzyl derivatives did not directly activate Mn-SOD but promoted SIRT3 proteins.In addition,HaCaT cells were irradiated with UV-B to induce an oxidative stress model in vitro to further verify the effect of bibenzyl derivatives.The results show that bibenzyl derivatives could directly bind to SIRT3,enhance the deacetylation and then activate Mn-SOD,so as to protect UV-B induced skin photoaging.展开更多
Five novel(9,10-dihydro)phenanthrene and bibenzyl trimers,as well as two previously identified biphenanthrenes and bibenzyls,were isolated from the tubers of Bletilla striata.Their structures were elucidated through c...Five novel(9,10-dihydro)phenanthrene and bibenzyl trimers,as well as two previously identified biphenanthrenes and bibenzyls,were isolated from the tubers of Bletilla striata.Their structures were elucidated through comprehensive analyses of NMR and HRESIMS spectroscopic data.The absolute configurations of these compounds were determined by calculating rotational energy barriers and comparison of experimental and calculated ECD curves.Compounds 5b and 6 exhibited inhibitory effects on LPS-induced NO production in BV-2 cells,with IC_(50) values of 12.59±0.40 and 15.59±0.83μmol·L^(-1),respectively.A mechanistic study suggested that these compounds may attenuate neuroinflammation by reducing the activation of the AKT/IκB/NF-κB signaling pathway.Additionally,compounds 3a,6,and 7 demonstrated significant PTP1B inhibitory activities,with IC_(50) values of 1.52±0.34,1.39±0.11,and 1.78±0.01μmol·L^(-1),respectively.Further investigation revealed that compound 3a might inhibit LPS-induced PTP1B overexpression and NF-κB activation,thereby mitigating the neuroinflammatory response in BV-2 cells.展开更多
Bioassay-guided fractionation of the diethyl ether extract of the liverwort Asterella angusta led to the isolation of two antifungal bis(bibenzyl)s, riccardin I (1), and angustatin A (2). Their structures were e...Bioassay-guided fractionation of the diethyl ether extract of the liverwort Asterella angusta led to the isolation of two antifungal bis(bibenzyl)s, riccardin I (1), and angustatin A (2). Their structures were established by spectroscopic analysis (1D NMR and 2D NMR, IR, MS). Compound I is a novel variant riccardin-type bis(bibenzyl), while compound 2 is the first nonheteratom-containing variant bis(bibenzyl) possessing a bibenzyl-phenanthrene skeleton.展开更多
基金Supported by Science and Technology Committee of Shanghai, P R China(No 036505003)
文摘As a part of the ongoing search for new constituents of Stemona species in China, chemical investigation of Stemona sessilifolia, a plant used in the traditional Chinese medicine to treat respiratory disorders, was carried out. To identify the chemical components rapidly, a selected sample of S. sessilifolia containing bibenzyls was tested using LC-ESIMS and analyzed further using stop-flow LC-UV-NMR, which was sensitive for the detection of the main constituents. LC microfractions were collected using the LC-UV-NMR technique and HR-EIMS off-line analysis was cartied out on the collected fractions. This chemical screening strategy allowed for the on-line identification of the main constituents of S. sessilifolia and provided information that was useful for a further peak-guided isolation procedure. Using these methods, four bibenzyls were isolated: two known compounds, 3,5-dihydroxy-4-methyl bibenzyl(1) and 3, 5-dihydroxy-2'-methoxy-4-methyl bibenzyl ( 2 ), and two novel compounds, 3,3'-dihydroxy-5, 6'-dimethoxy bibenzyl(3) and 3,5-dihydroxy-2', 5'-dimethoxy bibenzyl (4).
基金supported by the National Key Research and Development Program of China(2020YFA0908000)CAMS Innovation fund for Medical Sciences(CIFMS-2021-I2M1-028 and CIFMS-2021-I2M-1-029,China)Beijing Key Laboratory of non-Clinical Drug Metabolism and PK/PD Study(Z141102004414062,China)。
文摘Bibenzyls,a kind of important plant polyphenols,have attracted growing attention for their broad and remarkable pharmacological activities.However,due to the low abundance in nature,uncontrollable and environmentally unfriendly chemical synthesis processes,these compounds are not readily accessible.Herein,one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes.Three types of efficiently postmodifying modular strains were engineered by employing methyltransferases,prenyltransferase,and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules.Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes.Especially,a prenylated bibenzyl derivative(12)was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke.RNA-seq,quantitative RT-PCR,and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor,mitochondria associated 3(Aifm3),suggesting that Aifm3 might be a new target in ischemic stroke therapy.This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.
基金Project supported by the National Natural Science Foundation of China (No. QT program 20021001) and the Natural Science Foundation of Gansu province (ZS011-A25-003-Z).
文摘The Ramberg-Bcklund rearrangement has been successfully utilized to convert readily available - and -hydrogen bearing substituted dibenzyl sulfones into corresponding stilbene derivatives, which is conveniently followed by hydrogenation in the presence of 10% Pd/C to afford the natural bibenzyls.
文摘A new bibenzyl derivative, 3,4-dihydroxy-4,5-dimethoxy bibenzyl, was isolated from a orchid Dendrobium moniliforme. The structure elucidation and 1H,13C NMR assignments were achieved by spectroscopic method.
文摘A new bibenzyl derivative 1, named 2-(4''-hydroxybenzy1)-3-(3'-hydroxyphenethy1)-5-methoxy-cyclohexa-2,5-diene-1,4- dione, and two known stilbenoids (2, 3) were isolated from the tubers of Pleione bulbocodioides (Franch.) Rolfe. Their structures were elucidated by spectroscopic methods.
基金National Natural and Science Foundations of China(No.30800090)"Xi-Bu-Zhi-Guang"project(2009-2012)from Chinese Academy of Science and the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2010-ZZ012).
文摘15 compounds,including two new ones crepidatuols A(1)and B(2)were isolated from the stems of Dendrobium crepidatum.The planar structures of these compounds were elucidated by spectroscopic methods(NMR,MS,UV,and IR)and comparison with those from literatures.10 compounds were send for enhancing activities on nerve growth factor(NGF)medicated neurite outgrowth in PC12 cells and the results indicated that crepidatuol A(1),confusarin and 3-(2-acetoxy-5-methoxy)-phenylpropanol showed enhancing activities at the concentration of 10.0μM.
文摘A new bibenzyl glycoside has been isolated from the stems of Dendrobium moniliforme (L.) Sw. (Orchidaceae). Its structure has been identified on the basis of spectroscopic and chemical methods.
基金supported by Biological Resources Programme,Chinese Academy of Sciences (Grant No.KFJ-BRP-007-019)National Natural Science Foundation of China (No.32170407) and Beijing DR PLANT Biotechnology Co.,Ltd.
文摘Dendrobium officinale is a valuable medicinal herb that is widely used in traditional Chinese medicine.The chemical constituents of D.officinale have attracted much attention and a large number of compounds have been reported including many bibenzyl derivatives.13 bibenzyl derivatives from D.officinale were sent for molecular docking,sur-face plasmon resonance(SPR)assay and after detection of Mn-SOD and SIRT3 activities in or not in HaCaT cells,it was concluded that bibenzyl derivatives did not directly activate Mn-SOD but promoted SIRT3 proteins.In addition,HaCaT cells were irradiated with UV-B to induce an oxidative stress model in vitro to further verify the effect of bibenzyl derivatives.The results show that bibenzyl derivatives could directly bind to SIRT3,enhance the deacetylation and then activate Mn-SOD,so as to protect UV-B induced skin photoaging.
基金This research was supported by the National Natural Science Foundation of China(No.81903488)the CAMS Innovation Fund for Medical Sciences(No.CIFMS-2021-I2M-1-026)。
文摘Five novel(9,10-dihydro)phenanthrene and bibenzyl trimers,as well as two previously identified biphenanthrenes and bibenzyls,were isolated from the tubers of Bletilla striata.Their structures were elucidated through comprehensive analyses of NMR and HRESIMS spectroscopic data.The absolute configurations of these compounds were determined by calculating rotational energy barriers and comparison of experimental and calculated ECD curves.Compounds 5b and 6 exhibited inhibitory effects on LPS-induced NO production in BV-2 cells,with IC_(50) values of 12.59±0.40 and 15.59±0.83μmol·L^(-1),respectively.A mechanistic study suggested that these compounds may attenuate neuroinflammation by reducing the activation of the AKT/IκB/NF-κB signaling pathway.Additionally,compounds 3a,6,and 7 demonstrated significant PTP1B inhibitory activities,with IC_(50) values of 1.52±0.34,1.39±0.11,and 1.78±0.01μmol·L^(-1),respectively.Further investigation revealed that compound 3a might inhibit LPS-induced PTP1B overexpression and NF-κB activation,thereby mitigating the neuroinflammatory response in BV-2 cells.
基金supported by the National Natural Science Foundation of China(No.30925038)
文摘Bioassay-guided fractionation of the diethyl ether extract of the liverwort Asterella angusta led to the isolation of two antifungal bis(bibenzyl)s, riccardin I (1), and angustatin A (2). Their structures were established by spectroscopic analysis (1D NMR and 2D NMR, IR, MS). Compound I is a novel variant riccardin-type bis(bibenzyl), while compound 2 is the first nonheteratom-containing variant bis(bibenzyl) possessing a bibenzyl-phenanthrene skeleton.