Objective:To validate scientifically the traditional use of Salacia leptoclada Tul.(Celastraceae)(S.leptoclada)and to isolate and elucidate the structure of the biologically active compound.Methods:Bioassay-guided fra...Objective:To validate scientifically the traditional use of Salacia leptoclada Tul.(Celastraceae)(S.leptoclada)and to isolate and elucidate the structure of the biologically active compound.Methods:Bioassay-guided fractionation of the acetonic extract of the stem barks of S.leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models.The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry.Results:Biological screening of S.leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide.The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC_(50)value of(0.041±0.020)μg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC_(50)value of(0.052±0.030)μg/mL.Despite this interesting anti-malarial property of the lead compound,the therapeutic index was weak(0.788).In the best of our knowledge,the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S.leptoclada.Conclusions:The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug.展开更多
Divergent synthesis of medium-sized rings with controllable ring sizes represents a longstanding challenge in organic synthesis.Herein,we developed a transition-metal-catalyzed switchable divergent cycloaddition of pa...Divergent synthesis of medium-sized rings with controllable ring sizes represents a longstanding challenge in organic synthesis.Herein,we developed a transition-metal-catalyzed switchable divergent cycloaddition of para-quinone methides and vinylethylene carbonates by controlling the steric hindrance of substituent.Different from reported alkoxide-triggered annulations,this process undergoes a regiodivergent allylation of para-quinone methides followed by 1,6-addition reaction,providing a new route to selectively synthesize seven-to ten-membered nitrogen-containing heterocycles in high yields with excellent regioselectivities.This protocol features a broad substrate scope,wide functional group tolerance as well as operational simplicity.The reaction mechanism was investigated by conducting a series of control experiments as well as DFT calculations and the origins of the regioselectivities of the cycloaddition process were rationalized.展开更多
A photoinduced reaction of potassium alkyltrifluoroborates,sulfur dioxide,and para-quinone methides under visible light irradiation at room temperature is developed,giving rise to diarylmethyl alkylsulfones in moderat...A photoinduced reaction of potassium alkyltrifluoroborates,sulfur dioxide,and para-quinone methides under visible light irradiation at room temperature is developed,giving rise to diarylmethyl alkylsulfones in moderate to good yields.This reaction works well under photocatalysis with a broad substrate scope by using DABCO·(SO_(2))_(2)as the source of sulfur dioxide.Mechanistic study shows that this transformation is initiated by alkyl radicals generated in situ from potassium alkyltrifluoroborates in the presence of photocatalyst.The subsequent insertion of sulfur dioxide and radical 1,6-addition of para-quinone methides with alkylsulfonyl radical intermediates afford the corresponding diarylmethyl alkylsulfones.展开更多
The cascade O-insertion/1,6 conjugate addition between benzynes and ortho-hydroxyphenyl substituted para-quinone methides has been reported, affording 9-phenol substituted xanthenes in 49%-84% yields.
A novel organocatalytic cascade process initiated by 1,6-conjugated addition has been successfully developed. A range of pharmaceutically active 2-amino-4-aryl-4H-chromenes were readily obtained in high yields（88%-99...A novel organocatalytic cascade process initiated by 1,6-conjugated addition has been successfully developed. A range of pharmaceutically active 2-amino-4-aryl-4H-chromenes were readily obtained in high yields（88%-99%） and excellent enantiopurities（86%-99% ee）. The functionalized para-Quinone methides（p-OMs） could be facilely obtained.展开更多
A visible light and base promoted O-H insertion/cyclization of para-quinone methides with aryl diazoacetates is developed. This one-pot two step reaction offers a mild and efficient approach for the synthesis of biolo...A visible light and base promoted O-H insertion/cyclization of para-quinone methides with aryl diazoacetates is developed. This one-pot two step reaction offers a mild and efficient approach for the synthesis of biologically important 2,3-dihydrobenzofuran derivatives in good yields and moderate diastereoselectivities.展开更多
Given the significance of oxacyclic frameworks in molecular scaffolds and drug discovery,it is intriguing to precisely construct and manipulate such ring systems in chemical research.In this area,the intermolecular,mu...Given the significance of oxacyclic frameworks in molecular scaffolds and drug discovery,it is intriguing to precisely construct and manipulate such ring systems in chemical research.In this area,the intermolecular,multicomponent cyclization for the synthesis of diversely substituted seven-membered ring oxacycles under simple conditions is still a challenge.Here,we report a dual photoredox/Brønsted acid relay catalytic strategy for in situ generation of ortho-quinone methides and subsequent(4+3)cyclization with 2-indolylalcohols.In this one-pot multicomponent reaction,two C-C and one C-O bonds are formed,providing de novo access to various biologically important indole-fused,oxygen-containing seven-membered heterocycles.By virtue of a chiral phosphoric acid,an asymmetric version can also be achieved with good to excellent levels of enantioselectivity(up to 96:4 er).展开更多
Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic ac...Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substi- tuent has been placed para to the nascent exo-methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5＇-aminohex- yloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.展开更多
Chromenes represent an important class of six-membered heterocycles and have drawn tremendous attention in recent years. In this article, we report a convenient and practical synthesis of this heterocycle by a silver(...Chromenes represent an important class of six-membered heterocycles and have drawn tremendous attention in recent years. In this article, we report a convenient and practical synthesis of this heterocycle by a silver(I)-catalyzed cycloaddition reaction between in situ generated ortho-quinone methides and N-allenamides. Diverse 4H-chromenes were synthesized in good to excellent yields under very mild conditions.展开更多
A formal[4+3]-cycloaddition reaction of ortho-hydroxyphenyl-substituted para-quinone methides(p-QMs)with in-situ generated azaoxyallyl cations is reported.The reaction occurs under very mild reaction conditions(transi...A formal[4+3]-cycloaddition reaction of ortho-hydroxyphenyl-substituted para-quinone methides(p-QMs)with in-situ generated azaoxyallyl cations is reported.The reaction occurs under very mild reaction conditions(transition-metal free,room temperature,cheap inorganic base)and provides a very efficient route to a series of biologically important 1,4-benzoxazepine derivatives in good to excellent yields.展开更多
A novel,efficient and pragmatic method to prepare gem-diboron products with vicinal tertiary/quaternary stereocenters using LiTMP-mediated 1,6-conjugate addition of gem-diborylalkanes to para-quinone methides was desc...A novel,efficient and pragmatic method to prepare gem-diboron products with vicinal tertiary/quaternary stereocenters using LiTMP-mediated 1,6-conjugate addition of gem-diborylalkanes to para-quinone methides was described for the first time.The results showed that various gem-diboron products with vicinal tertiary and quaternary stereocenters could be formed within 15 min at ambient temperature.This simple protocol has also been applied for the efficient synthesis of the analogue of Bedaquiline.展开更多
A concise synthesis of 2-(2-hydroxyphenyl)acetonitriles has been developed through reaction of trimethylsilyl cyanide and the o-quinone methides in situ generated from 2-(1-tosylalkyl)phenols under basic conditions.In...A concise synthesis of 2-(2-hydroxyphenyl)acetonitriles has been developed through reaction of trimethylsilyl cyanide and the o-quinone methides in situ generated from 2-(1-tosylalkyl)phenols under basic conditions.In addition,2-(2-hydroxyphenyl)acetonitriles could be conveniently transformed to benzofuranones.展开更多
-According to basic equations of fluid mechanics, this paper presents a unified variational principle of fluid mechanics (UVPFM) by using the optimization method of weighted residuals (OMWR). The advantages are as fol...-According to basic equations of fluid mechanics, this paper presents a unified variational principle of fluid mechanics (UVPFM) by using the optimization method of weighted residuals (OMWR). The advantages are as follows, the establishment of the functional and the variational principle is easy, it can change various problems of fluid mechanics derived by basic equations into a unified optimization problem, and the solution is the optimum one in some sense. According to the OMWR for the solitary subdomain, this paper uses UVPFM onto any solitary subdomain and gives the solution of the hydrodynamics equation which is suitable only for that solitary subdomain. According to the OMWR for solitary point, this paper uses UVPFM to any solitary point and gives the solution of the hydrodynamics equation (point solution) which is suitable only for that solitary point. As the solution for the solitary subdomain or solitary point is developed independently, the compatibility with other subdomain or other points, does not need to be considered, but all the boundary conditions and the supplementary derived residual equations obtained by running the derivative operations to the differential equation should be taken into account.展开更多
基金Supported by the Third World Academy of Science(TWAS)Fellowship for Research and Advanced Training FR number:Grant No.3240224121the International Foundation for Science dFS,Stockholm.Swedem and the Organization for the Prohibition of Chemical Weapons(OPCW)dFS Research Grant No.F/4921-2)
文摘Objective:To validate scientifically the traditional use of Salacia leptoclada Tul.(Celastraceae)(S.leptoclada)and to isolate and elucidate the structure of the biologically active compound.Methods:Bioassay-guided fractionation of the acetonic extract of the stem barks of S.leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models.The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry.Results:Biological screening of S.leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide.The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC_(50)value of(0.041±0.020)μg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC_(50)value of(0.052±0.030)μg/mL.Despite this interesting anti-malarial property of the lead compound,the therapeutic index was weak(0.788).In the best of our knowledge,the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S.leptoclada.Conclusions:The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug.
基金supportedbythe National Natural Science Foundation of China(Nos.82173664,81803342)“Shuang Chuang”Research Team of jiangsu Province(No.20182036).
文摘Divergent synthesis of medium-sized rings with controllable ring sizes represents a longstanding challenge in organic synthesis.Herein,we developed a transition-metal-catalyzed switchable divergent cycloaddition of para-quinone methides and vinylethylene carbonates by controlling the steric hindrance of substituent.Different from reported alkoxide-triggered annulations,this process undergoes a regiodivergent allylation of para-quinone methides followed by 1,6-addition reaction,providing a new route to selectively synthesize seven-to ten-membered nitrogen-containing heterocycles in high yields with excellent regioselectivities.This protocol features a broad substrate scope,wide functional group tolerance as well as operational simplicity.The reaction mechanism was investigated by conducting a series of control experiments as well as DFT calculations and the origins of the regioselectivities of the cycloaddition process were rationalized.
基金Financial support from the National Natural Science Foundation of China(Nos.22007017 and 21871053)the Talents'Startup Fund of Gannan Medical University(No.QD201831)+3 种基金the Education Bureau of Jiangxi Province(No.GJJ190799)the Research Fund of Gannan Medical University(No.ZD201905)the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2019R01005)the Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University(No.2020ZD04)。
文摘A photoinduced reaction of potassium alkyltrifluoroborates,sulfur dioxide,and para-quinone methides under visible light irradiation at room temperature is developed,giving rise to diarylmethyl alkylsulfones in moderate to good yields.This reaction works well under photocatalysis with a broad substrate scope by using DABCO·(SO_(2))_(2)as the source of sulfur dioxide.Mechanistic study shows that this transformation is initiated by alkyl radicals generated in situ from potassium alkyltrifluoroborates in the presence of photocatalyst.The subsequent insertion of sulfur dioxide and radical 1,6-addition of para-quinone methides with alkylsulfonyl radical intermediates afford the corresponding diarylmethyl alkylsulfones.
基金supported by the National Natural Science Foundation of China(No. 21462034)the Young Scientists Foundation of Shihezi University(Nos. RCZX201546, 2015ZRKXJQ05)the Excellent Young Teachers Plan of Bingtuan(No. CZ027203)
文摘The cascade O-insertion/1,6 conjugate addition between benzynes and ortho-hydroxyphenyl substituted para-quinone methides has been reported, affording 9-phenol substituted xanthenes in 49%-84% yields.
基金financially supported by the National Natural Science Foundation of China(No.21402163)the Fundamental Research Funds for the Central Universities of Southwest Minzu University (No. 2016NGJPY02)+1 种基金the Graduate Innovation Project of Southwest Minzu University (No. CX2017SZ016)the Undergraduate Innovation Project of Southwest Minzu University (No. S201610656092)
文摘A novel organocatalytic cascade process initiated by 1,6-conjugated addition has been successfully developed. A range of pharmaceutically active 2-amino-4-aryl-4H-chromenes were readily obtained in high yields（88%-99%） and excellent enantiopurities（86%-99% ee）. The functionalized para-Quinone methides（p-OMs） could be facilely obtained.
基金the National Natural Science Foundation of China (Nos.21971001,21702001)the Start-up Grant from Anhui University for financial support of this work。
文摘A visible light and base promoted O-H insertion/cyclization of para-quinone methides with aryl diazoacetates is developed. This one-pot two step reaction offers a mild and efficient approach for the synthesis of biologically important 2,3-dihydrobenzofuran derivatives in good yields and moderate diastereoselectivities.
基金the financial support from the National Natural Science Foundation of China(Nos.21971081,22171099,21820102003,91956201,22203034,and 92256301)the Nation Key R&D Program of China(No.2022YFA1506100)+3 种基金the Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University,China(No.2021YB02)the Knowledge Innovation Program of Wuhan-Basic Research(No.2022013301015173)the Double-Thousand Talents Plan of Jiangxi Province,China(No.jxsq2023102004)the Program of Introducing Talents ofDiscipline toUniversities of China(No.111 Program,B17019).
文摘Given the significance of oxacyclic frameworks in molecular scaffolds and drug discovery,it is intriguing to precisely construct and manipulate such ring systems in chemical research.In this area,the intermolecular,multicomponent cyclization for the synthesis of diversely substituted seven-membered ring oxacycles under simple conditions is still a challenge.Here,we report a dual photoredox/Brønsted acid relay catalytic strategy for in situ generation of ortho-quinone methides and subsequent(4+3)cyclization with 2-indolylalcohols.In this one-pot multicomponent reaction,two C-C and one C-O bonds are formed,providing de novo access to various biologically important indole-fused,oxygen-containing seven-membered heterocycles.By virtue of a chiral phosphoric acid,an asymmetric version can also be achieved with good to excellent levels of enantioselectivity(up to 96:4 er).
文摘Biological application of conjugates derived from oligonucleotides and quinone methides have pre- viously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substi- tuent has been placed para to the nascent exo-methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5＇-aminohex- yloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.
基金supported by the National Natural Science Foundation of China(21572118,21750110444)the Natural Science Foundation of Shandong Province(ZR2018MB010)+1 种基金subject construction funds(104.205.2.5)Tang scholar award of Shandong University
文摘Chromenes represent an important class of six-membered heterocycles and have drawn tremendous attention in recent years. In this article, we report a convenient and practical synthesis of this heterocycle by a silver(I)-catalyzed cycloaddition reaction between in situ generated ortho-quinone methides and N-allenamides. Diverse 4H-chromenes were synthesized in good to excellent yields under very mild conditions.
基金the National Natural Science Foundation of China(21971001,21702001)the Natural Science Foundation of Anhui Province(1808085MB47)+2 种基金the Open Fund for Discipline ConstructionInstitute of Physical Science and Information TechnologyAnhui University and the Start-up Grant from Anhui University。
文摘A formal[4+3]-cycloaddition reaction of ortho-hydroxyphenyl-substituted para-quinone methides(p-QMs)with in-situ generated azaoxyallyl cations is reported.The reaction occurs under very mild reaction conditions(transition-metal free,room temperature,cheap inorganic base)and provides a very efficient route to a series of biologically important 1,4-benzoxazepine derivatives in good to excellent yields.
基金The authors are grateful for the financial support provided by the National Natural Science Foundation of China(No.22001203)the startup funds from Xi'an Jiaotong University.The authors thank Dr.Lu Bai and Ms.Chao Feng from the Instrument Analysis Center of Xi'an Jiaotong University for their assistance with HRMS and NMR analysis.
文摘A novel,efficient and pragmatic method to prepare gem-diboron products with vicinal tertiary/quaternary stereocenters using LiTMP-mediated 1,6-conjugate addition of gem-diborylalkanes to para-quinone methides was described for the first time.The results showed that various gem-diboron products with vicinal tertiary and quaternary stereocenters could be formed within 15 min at ambient temperature.This simple protocol has also been applied for the efficient synthesis of the analogue of Bedaquiline.
基金the National Natural Science Foundation of China(21125208&20921092)National Basic Research Program of China(2010CB833300).
文摘A concise synthesis of 2-(2-hydroxyphenyl)acetonitriles has been developed through reaction of trimethylsilyl cyanide and the o-quinone methides in situ generated from 2-(1-tosylalkyl)phenols under basic conditions.In addition,2-(2-hydroxyphenyl)acetonitriles could be conveniently transformed to benzofuranones.
文摘-According to basic equations of fluid mechanics, this paper presents a unified variational principle of fluid mechanics (UVPFM) by using the optimization method of weighted residuals (OMWR). The advantages are as follows, the establishment of the functional and the variational principle is easy, it can change various problems of fluid mechanics derived by basic equations into a unified optimization problem, and the solution is the optimum one in some sense. According to the OMWR for the solitary subdomain, this paper uses UVPFM onto any solitary subdomain and gives the solution of the hydrodynamics equation which is suitable only for that solitary subdomain. According to the OMWR for solitary point, this paper uses UVPFM to any solitary point and gives the solution of the hydrodynamics equation (point solution) which is suitable only for that solitary point. As the solution for the solitary subdomain or solitary point is developed independently, the compatibility with other subdomain or other points, does not need to be considered, but all the boundary conditions and the supplementary derived residual equations obtained by running the derivative operations to the differential equation should be taken into account.
