A novel diterpenoid with an unprecedented 5/6/5/7 tetracyclic system, rhodauricanol A(1), five new grayanane-derived diterpenoids, dauricanols A-E(2-6), and five known ones(7-11) were isolated from the flowers of Rhod...A novel diterpenoid with an unprecedented 5/6/5/7 tetracyclic system, rhodauricanol A(1), five new grayanane-derived diterpenoids, dauricanols A-E(2-6), and five known ones(7-11) were isolated from the flowers of Rhododendron dauricum. Rhodauricanol A(1) possesses a unique 5/6/5/7 tetracyclic ring system featuring a 16-oxa-tetracyclo[11.2.1.0^(1,5).0^(7,13)]hexadecane core. Dauricanols A-C(2-4) are the first1,3-dioxolane conjugates of grayanane diterpenoids and 5-hydroxymethylfurfural and vanillin, respectively, and dauricanols D(5) and E(6) represent the first examples of 6-deoxy-1,5-seco-grayanane diterpenoids. Their structures were determined by spectroscopic methods, quantum chemical calculation including ^(13)C NMR-DP4+ analysis and ECD calculation, and single-crystal X-ray diffraction analysis. Plausible biosynthetic pathways for 1-4 were proposed. All the isolates showed significant analgesic activities,and dauricanols B(3) and C(4) showed more potent analgesic activities than the positive control, morphine.展开更多
We herein present the efficient syntheses,crystal structures,and physical properties of a series of novel benzene triimide(BTI)radical anions,emphasizing the relationship between molecular structure with spin–spin in...We herein present the efficient syntheses,crystal structures,and physical properties of a series of novel benzene triimide(BTI)radical anions,emphasizing the relationship between molecular structure with spin–spin intermolecular interactions and physical properties in the crystalline state.BTI radical crystals were preparedby reducingvarious substitutedBTIs(1)with cobaltocene(CoCp2),followed by sequential crystallization processes.Two isolable radical species,that is,neutral molecule-radical anion pair(2)and monoradical species(3),were obtained from BTIs bearing small substituents(ethyl and propyl),while for those bearing larger substituents(butyl,hexyl,and benzyl)sole monoradicals(3)were produced.The radical species showed diverse intermolecular stackings in the crystalline state referred to asπ-pimer,π-dimer,alternatingπ-trimer,and one-dimensional(1D)slippedπ-stacks depending on the length and size of the substituents.Different spin–spin interactions arising from the substituent-tuned radical packings were demonstrated by electron spin resonance(ESR)spectra.The structure–property relationshipwas studied in terms of magnetism and conductivity.The radicalπ-pimers andπ-stacks with effective charge transport exhibited paramagnetic property and conductivity feasibly at room temperature,whileπ-dimers andπ-trimers featuring thermally populated spin-triplet stateswere antiferromagnetic and nonconductive due to their strong radical–radical pairing effect.展开更多
Six highly oxygenated dimeric grayanane diterpenoids(1—6)including three new ones,bismollethers A—C(1—3),were isolated from the flowers of Rhododendron molle collected at Qichun,Hubei,China.The structures and relat...Six highly oxygenated dimeric grayanane diterpenoids(1—6)including three new ones,bismollethers A—C(1—3),were isolated from the flowers of Rhododendron molle collected at Qichun,Hubei,China.The structures and relative configurations of 1—6 were determined by comprehensive spectroscopic data analysis and 13C NMR calculation with DP4+analysis.The absolute configurations of bismollethers A—C(1—3)and birhodomollein B(5)were indubitably assigned by single-crystal X-ray diffraction analysis,revealing the head-to-tail linking manner of diterpenoid monomers.Bismollether A(1)is a caged dimeric grayanane diterpenoid linked through two oxygen-bridges of C-2−O−C-14′and C-14−O−C-2′,featuring a unique 1,8-dioxacyclotetradecane motif.The plausible biosynthesis pathways of 1—6 are proposed.All the isolates displayed significant analgesic activities and their structure-activity relationships were discussed.Grayanane diterpenoid dimers were found to be TRPV1 and TRPA1 dual antagonists,and docking studies provide a structural basis to design potent analgesics.展开更多
It is of vital importance to design efficient and low-cost bifunctional catalysts for the electrochemical water splitting under alkaline and neutral pH conditions.In this work,we report an efficient and stable NiCo_(2...It is of vital importance to design efficient and low-cost bifunctional catalysts for the electrochemical water splitting under alkaline and neutral pH conditions.In this work,we report an efficient and stable NiCo_(2)S_(4)/N,S co-doped reduced graphene oxide(NCS/NS-rGO)electrocatalyst for water splitting,in which NCS microspheres are composed of one-dimentional(1D)nanorods grown homogeneously on the surface of NS-rGOs).The synergetic effect,abundant active sites,and hybridization of NCS/NS-rGO endow their outstanding electrocatalytic performance for hydrogen evolution reaction(HER)and oxygen evolution reaction(OER)in both alkaline and neutral conditions.Furthermore,NCS/NS-rGO employed as both anode and cathode in a two-electrode alkaline and neutral system electrolyzers deliver 10 mA/cm^(2) with the low cell voltage of 1.58 V in alkaline and 1.91 V in neutral condition.These results illustrate the rational design of carbon-supported nickel-cobalt based bifunctional materials for practical water splitting over a wide pH range.展开更多
Kalmane diterpenoids,featuring a 5/8/5/5 tetracyclic carbon skeleton,are very rare in nature.The flowers of Rhododendron dauricum L.(Ericaceae)were phytochemically investigated for the first time,leading to the isolat...Kalmane diterpenoids,featuring a 5/8/5/5 tetracyclic carbon skeleton,are very rare in nature.The flowers of Rhododendron dauricum L.(Ericaceae)were phytochemically investigated for the first time,leading to the isolation of eight kalmane diterpenoids(1-8)including four new ones,named rhodokalmanols A-D(1-4).The structures of 1-8 were elucidated by comprehensive spectroscopic methods and ic NMR-DP4+analysis,and the absolute configurations of 1,2,4,and 5 were defined by single-crystal X-ray diffraction analysis with Cu Kαradiation.Rhodokalmanol A(1)represents the first 5,8-epoxykalmane diterpenoid and also the first kalm-15(16)-ene diterpenoid.Rhodokalmanols BD(2-4)are the first examples of kalm-7(8)-ene,kalm-16(17)-ene,and 8α-methoxykalmane diterpenoids,respectively.All the isolated kalmane diterpenoids 1-8 exhibited significant analgesic effects,and rhodokalmanol C(3)and kalmanoi(8)expressed more potent analgesic activity than morphine at doses of 0.2 and 0.04 mg/kg.The preliminary structure-activity relationships of kalmane diterpenoids as potent analgesics are discussed.展开更多
Main observation and conclusion Fifteen 5,9-epoxygrayanane diterpenoids(1-15)including fourteen new ones,epoxymicranthols A-N(1-14),were isolated from the leaves extract of Rhododendron micranthum.Their structures wer...Main observation and conclusion Fifteen 5,9-epoxygrayanane diterpenoids(1-15)including fourteen new ones,epoxymicranthols A-N(1-14),were isolated from the leaves extract of Rhododendron micranthum.Their structures were elucidated via extensive spectroscopic methods and ^(13)C NMR-DP4+analysis,and the absolute configurations of 1,3-10,14,and 15 were confirmed by single-crystal X-ray diffraction analysis.展开更多
Anemarrhena asphodeloides is an immensely popular medicinal herb in China,which contains an abundant of mangiferin.As an important bioactive xanthone C-glycoside,mangiferin possesses a variety of pharmacological activ...Anemarrhena asphodeloides is an immensely popular medicinal herb in China,which contains an abundant of mangiferin.As an important bioactive xanthone C-glycoside,mangiferin possesses a variety of pharmacological activities and is derived from the cyclization reaction of a benzophenone C-glycoside(maclurin).Biosyntheti-cally,C-glycosyltransferases are critical for the formation of benzophenone C-glycosides.However,the benzo-phenone C-glycosyltransferases from Anemarrhena asphodeloides have not been discovered.Herein,a promiscuous C-glycosyltransferase(AaCGT)was identified from Anemarrhena asphodeloides.It was able to catalyze efficiently mono-C-glycosylation of benzophenone,together with di-C-glycosylation of dihydrochalcone.It also exhibited the weak O-glycosylation or potent S-glycosylation capacities toward 12 other types of flavonoid scaffolds and a simple aromatic compound with–SH group.Homology modeling and mutagenesis experiments revealed that the glycosylation reaction of AaCGT was initiated by the conserved residue H23 as the catalytic base.Three critical residues H356,W359 and D380 were involved in the recognition of sugar donor through hydrogen-bonding interactions.In particular,the double mutant of F94W/L378M led to an unexpected enzy-matic conversion of mono-C-to di-C-glycosylation.This study highlights the important value of AaCGT as a potential biocatalyst for efficiently synthesizing high-value C-glycosides.展开更多
lIn response to the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)pandemic,over 200 vaccine candidates againstcoronavirus disease 2019(COVID-2019)are under development and currently moving forward at an u...lIn response to the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)pandemic,over 200 vaccine candidates againstcoronavirus disease 2019(COVID-2019)are under development and currently moving forward at an unparalleled speed.Theavailability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates,which is crucial to control COVID-19 pandemic.Several phase 3 efficacy trials of COVID-19 vaccine candidates are underway,which provide opportunities for the determination of COVID-19 correlates of protection.In this paper,we review currentknowledge for existence of COVD-19 correlates of protection,methods for assessment of immune correlates of protection andissues related to COVID-19 correlates of protection.展开更多
A large-scale vaccination of coronavirus disease-19(COVID-19)in adults has been conducted for nearly a year,and there is a growing recognition that immunization for children is also essential.It has been months since ...A large-scale vaccination of coronavirus disease-19(COVID-19)in adults has been conducted for nearly a year,and there is a growing recognition that immunization for children is also essential.It has been months since emergency use of pediatric COVID-19 vaccine was approved,we reviewed the prevalence and transmission of COVID-19 in children.The prevalence of COVID-19 in children is reduced due to vaccination even in a Delta prevalent period,so an increase in the vaccination rate is needed in children.Although the precise role of children in the transmission requires more research to uncover,they likely played a significant role,according to the available literature.We also described four candidate COVID-19 vaccines for children on their safety and immunogenicity and the impact of severe acute respiratory syndrome coronavirus 2 variants on childhood vaccination.Safety issues on pediatric vaccines post-approval,like adverse events following immunization and adverse events of special interest require studies on long-term and effective regulatory mechanisms.展开更多
基金supported by the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China (NoP2022-KF08)National Natural Science Foundation of China (Nos.22107033 and U1703109)the Scientific Research Project of Traditional Chinese Medicine of Hubei Provincial Health Commission (No. ZY2021M056)。
文摘A novel diterpenoid with an unprecedented 5/6/5/7 tetracyclic system, rhodauricanol A(1), five new grayanane-derived diterpenoids, dauricanols A-E(2-6), and five known ones(7-11) were isolated from the flowers of Rhododendron dauricum. Rhodauricanol A(1) possesses a unique 5/6/5/7 tetracyclic ring system featuring a 16-oxa-tetracyclo[11.2.1.0^(1,5).0^(7,13)]hexadecane core. Dauricanols A-C(2-4) are the first1,3-dioxolane conjugates of grayanane diterpenoids and 5-hydroxymethylfurfural and vanillin, respectively, and dauricanols D(5) and E(6) represent the first examples of 6-deoxy-1,5-seco-grayanane diterpenoids. Their structures were determined by spectroscopic methods, quantum chemical calculation including ^(13)C NMR-DP4+ analysis and ECD calculation, and single-crystal X-ray diffraction analysis. Plausible biosynthetic pathways for 1-4 were proposed. All the isolates showed significant analgesic activities,and dauricanols B(3) and C(4) showed more potent analgesic activities than the positive control, morphine.
基金This research was supported by the National Natural Science Foundation of China(no.91956126)Beijing National Laboratory for Molecular Sciences(BNLMS-CXXM-202002 and BMS Junior Fellow Scholarship)China Postdoctoral Science Foundation(no.2020TQ0326).
文摘We herein present the efficient syntheses,crystal structures,and physical properties of a series of novel benzene triimide(BTI)radical anions,emphasizing the relationship between molecular structure with spin–spin intermolecular interactions and physical properties in the crystalline state.BTI radical crystals were preparedby reducingvarious substitutedBTIs(1)with cobaltocene(CoCp2),followed by sequential crystallization processes.Two isolable radical species,that is,neutral molecule-radical anion pair(2)and monoradical species(3),were obtained from BTIs bearing small substituents(ethyl and propyl),while for those bearing larger substituents(butyl,hexyl,and benzyl)sole monoradicals(3)were produced.The radical species showed diverse intermolecular stackings in the crystalline state referred to asπ-pimer,π-dimer,alternatingπ-trimer,and one-dimensional(1D)slippedπ-stacks depending on the length and size of the substituents.Different spin–spin interactions arising from the substituent-tuned radical packings were demonstrated by electron spin resonance(ESR)spectra.The structure–property relationshipwas studied in terms of magnetism and conductivity.The radicalπ-pimers andπ-stacks with effective charge transport exhibited paramagnetic property and conductivity feasibly at room temperature,whileπ-dimers andπ-trimers featuring thermally populated spin-triplet stateswere antiferromagnetic and nonconductive due to their strong radical–radical pairing effect.
基金This work was supported by the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2022-KF08)the Fund of Laboratory of Xinjiang Native Medicinal and Edible Plant Resource Chemistry(KSUZDSYS202101)+2 种基金the National Natural Science Foundation of China(22107033 and U1703109)the Traditional Chinese Medicine of Hubei Provincial Health Commission(ZY2021M056)the China Postdoctoral Science Foundation(2021M691152)。
文摘Six highly oxygenated dimeric grayanane diterpenoids(1—6)including three new ones,bismollethers A—C(1—3),were isolated from the flowers of Rhododendron molle collected at Qichun,Hubei,China.The structures and relative configurations of 1—6 were determined by comprehensive spectroscopic data analysis and 13C NMR calculation with DP4+analysis.The absolute configurations of bismollethers A—C(1—3)and birhodomollein B(5)were indubitably assigned by single-crystal X-ray diffraction analysis,revealing the head-to-tail linking manner of diterpenoid monomers.Bismollether A(1)is a caged dimeric grayanane diterpenoid linked through two oxygen-bridges of C-2−O−C-14′and C-14−O−C-2′,featuring a unique 1,8-dioxacyclotetradecane motif.The plausible biosynthesis pathways of 1—6 are proposed.All the isolates displayed significant analgesic activities and their structure-activity relationships were discussed.Grayanane diterpenoid dimers were found to be TRPV1 and TRPA1 dual antagonists,and docking studies provide a structural basis to design potent analgesics.
基金supported by the National Natural Science Foundation of China(Nos.51962032,61704114,and 51764049)the Youth Innovative Talents Cultivation Fund,Shihezi University(No.KX01480109)the Opening Project of The Research Center for Material Chemical Engineering Technology of Xinjiang Bingtuan(No.2017BTRC007).
文摘It is of vital importance to design efficient and low-cost bifunctional catalysts for the electrochemical water splitting under alkaline and neutral pH conditions.In this work,we report an efficient and stable NiCo_(2)S_(4)/N,S co-doped reduced graphene oxide(NCS/NS-rGO)electrocatalyst for water splitting,in which NCS microspheres are composed of one-dimentional(1D)nanorods grown homogeneously on the surface of NS-rGOs).The synergetic effect,abundant active sites,and hybridization of NCS/NS-rGO endow their outstanding electrocatalytic performance for hydrogen evolution reaction(HER)and oxygen evolution reaction(OER)in both alkaline and neutral conditions.Furthermore,NCS/NS-rGO employed as both anode and cathode in a two-electrode alkaline and neutral system electrolyzers deliver 10 mA/cm^(2) with the low cell voltage of 1.58 V in alkaline and 1.91 V in neutral condition.These results illustrate the rational design of carbon-supported nickel-cobalt based bifunctional materials for practical water splitting over a wide pH range.
基金This work was financially supported by the Scientific Research Project of Traditional Chinese Medicine of Hubei Provincial Health Commission(ZY2021M056)the Open Project of State Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources(No.CMEMR-2021-B03)。
文摘Kalmane diterpenoids,featuring a 5/8/5/5 tetracyclic carbon skeleton,are very rare in nature.The flowers of Rhododendron dauricum L.(Ericaceae)were phytochemically investigated for the first time,leading to the isolation of eight kalmane diterpenoids(1-8)including four new ones,named rhodokalmanols A-D(1-4).The structures of 1-8 were elucidated by comprehensive spectroscopic methods and ic NMR-DP4+analysis,and the absolute configurations of 1,2,4,and 5 were defined by single-crystal X-ray diffraction analysis with Cu Kαradiation.Rhodokalmanol A(1)represents the first 5,8-epoxykalmane diterpenoid and also the first kalm-15(16)-ene diterpenoid.Rhodokalmanols BD(2-4)are the first examples of kalm-7(8)-ene,kalm-16(17)-ene,and 8α-methoxykalmane diterpenoids,respectively.All the isolated kalmane diterpenoids 1-8 exhibited significant analgesic effects,and rhodokalmanol C(3)and kalmanoi(8)expressed more potent analgesic activity than morphine at doses of 0.2 and 0.04 mg/kg.The preliminary structure-activity relationships of kalmane diterpenoids as potent analgesics are discussed.
基金This work was financially supported by the National Natural Science Foundation of China(No.U1703109).
文摘Main observation and conclusion Fifteen 5,9-epoxygrayanane diterpenoids(1-15)including fourteen new ones,epoxymicranthols A-N(1-14),were isolated from the leaves extract of Rhododendron micranthum.Their structures were elucidated via extensive spectroscopic methods and ^(13)C NMR-DP4+analysis,and the absolute configurations of 1,3-10,14,and 15 were confirmed by single-crystal X-ray diffraction analysis.
基金the National Natural Science Foundation of China No.81874333the Guangdong Foundation for Basic and Applied Basic Research No.2020A1515010926.
文摘Anemarrhena asphodeloides is an immensely popular medicinal herb in China,which contains an abundant of mangiferin.As an important bioactive xanthone C-glycoside,mangiferin possesses a variety of pharmacological activities and is derived from the cyclization reaction of a benzophenone C-glycoside(maclurin).Biosyntheti-cally,C-glycosyltransferases are critical for the formation of benzophenone C-glycosides.However,the benzo-phenone C-glycosyltransferases from Anemarrhena asphodeloides have not been discovered.Herein,a promiscuous C-glycosyltransferase(AaCGT)was identified from Anemarrhena asphodeloides.It was able to catalyze efficiently mono-C-glycosylation of benzophenone,together with di-C-glycosylation of dihydrochalcone.It also exhibited the weak O-glycosylation or potent S-glycosylation capacities toward 12 other types of flavonoid scaffolds and a simple aromatic compound with–SH group.Homology modeling and mutagenesis experiments revealed that the glycosylation reaction of AaCGT was initiated by the conserved residue H23 as the catalytic base.Three critical residues H356,W359 and D380 were involved in the recognition of sugar donor through hydrogen-bonding interactions.In particular,the double mutant of F94W/L378M led to an unexpected enzy-matic conversion of mono-C-to di-C-glycosylation.This study highlights the important value of AaCGT as a potential biocatalyst for efficiently synthesizing high-value C-glycosides.
基金supported by Jiangsu Province Special Funds for Key Research&Developm ent(2060499).
文摘lIn response to the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)pandemic,over 200 vaccine candidates againstcoronavirus disease 2019(COVID-2019)are under development and currently moving forward at an unparalleled speed.Theavailability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates,which is crucial to control COVID-19 pandemic.Several phase 3 efficacy trials of COVID-19 vaccine candidates are underway,which provide opportunities for the determination of COVID-19 correlates of protection.In this paper,we review currentknowledge for existence of COVD-19 correlates of protection,methods for assessment of immune correlates of protection andissues related to COVID-19 correlates of protection.
文摘A large-scale vaccination of coronavirus disease-19(COVID-19)in adults has been conducted for nearly a year,and there is a growing recognition that immunization for children is also essential.It has been months since emergency use of pediatric COVID-19 vaccine was approved,we reviewed the prevalence and transmission of COVID-19 in children.The prevalence of COVID-19 in children is reduced due to vaccination even in a Delta prevalent period,so an increase in the vaccination rate is needed in children.Although the precise role of children in the transmission requires more research to uncover,they likely played a significant role,according to the available literature.We also described four candidate COVID-19 vaccines for children on their safety and immunogenicity and the impact of severe acute respiratory syndrome coronavirus 2 variants on childhood vaccination.Safety issues on pediatric vaccines post-approval,like adverse events following immunization and adverse events of special interest require studies on long-term and effective regulatory mechanisms.