Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]iso...Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.展开更多
Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the con...Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.展开更多
Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficientl...Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficiently accomplished from the key intermediate(S)-6 with three contiguous stereocenters in 5 steps and the synthetic 1 induced G2/M-phase cell cycle arrest of HT29 cells and apoptosis of HL60 and NB4 cells by activation of caspase-3 and degradation of PARP.(S)-6,bearing three contiguous chiral centers,was efficiently constructed by a novel Nazarov cyclization reaction containing basic nitrogen,which was less developed,primarily due to the incompatibility of basic nitrogen under acidic reaction conditions.This reaction allows a wide range of pentadienone substrates containing basic nitrogen to undergo Nazarov cyclization in a single regioselective and diastereoselective manner and is capable of generating three stereocenters simultaneously.Furthermore,the mechanism of the Nazarov cyclization and the origin of the regio-and diastereoselectivity were elucidated by DFT calculations and deuteration experiments,providing valuable insights into the reaction and serving as a guide for future applications involving substrates containing basic nitrogen.展开更多
The Meinwald rearrangement has proven to be one of the most useful tools in organic synthesis.However,examples of asymmetric Meinwald rearrangements are quite scarce,and these reactions have so far been limited to the...The Meinwald rearrangement has proven to be one of the most useful tools in organic synthesis.However,examples of asymmetric Meinwald rearrangements are quite scarce,and these reactions have so far been limited to the use of chiral Br?nsted acids as catalysts.Here,we report a copper-catalyzed asymmetric cascade cyclization/Meinwald rearrangement reaction,allowing the practical and atom-economic synthesis of a range of chiral tricyclic pyrroles bearing a chiral oxa-quaternary carbon stereocenter in high yields and enantioselectivities.Thus,this protocol not only represents the first transition-metal-catalyzed enantioselective Meinwald rearrangement,but also constitutes the first example of asymmetric formal monocarbon insertion into C-O bond of ester.Moreover,theoretical calculations provide further evidence for this multiple cascade cyclization and elucidate the origin of enantioselectivity.展开更多
Early diagnosis and treatment of cancer requires the development of tools that are both sensitive and selective in detecting spermine.In this study,we presented a"supramolecular cyclization-induced emission enhan...Early diagnosis and treatment of cancer requires the development of tools that are both sensitive and selective in detecting spermine.In this study,we presented a"supramolecular cyclization-induced emission enhancement"strategy for the sensitive and selective detection of spermine.A new pillar[5]arene probe(P1)demonstrated excellent solution/solid dual-state emission properties,and the addition of certain spermine(Spm)resulted in fluorescence enhancement due to the synergy of multiple weak interactions that restricted the free motion of P1 in the P1⊃Spm complex.This mechanism was further confirmed by time-resolved spectroscopy,DFT calculations,and IGM analysis.With its low limit of detection and high selectivity,P1 is a promising tool for measuring spermine in artificial urine samples.展开更多
Cyclic polymers are a class of polymers that feature endless topology,and the synthesis of cyclic polymers has attracted the attention of many researchers.Herein,cyclic polymers were efficiently constructed by self-fo...Cyclic polymers are a class of polymers that feature endless topology,and the synthesis of cyclic polymers has attracted the attention of many researchers.Herein,cyclic polymers were efficiently constructed by self-folding cyclization technique at high concentrations.Linear poly((oligo(ethylene glycol)acrylate)-co-(dodecyl acrylate))(P(OEGA-co-DDA))precursors with different ratios of hydrophilic and hydrophobic moieties were synthesized by reversible addition-fragmentation chain transfer(RAFT)polymerization using a bifunctional chain transfer agent with two anthryl end groups.The amphiphilic linear precursors underwent the self-folding process to generate polymeric nanoparticles in water.By irradiating the aqueous solution of the nanoparticles with 365 nm UV light,cyclic polymers were synthesized successfully via coupling of anthryl groups.The effects of the ratios of hydrophilic and hydrophobic moieties in linear P(OEGA-co-DDA)copolymers and polymer concentration on the purity of the obtained cyclic polymers were explored in detail via ^(1)H nuclear magnetic resonance(^(1)H NMR),dynamic light scattering(DLS),UV‒visible(vis)analysis,three-detection size exclusion chromatography(TD-SEC)and transmission electron microscopy(TEM).It was found that by adjusting the content of the hydrophilic segments in linear precursors,single chain polymeric nanoparticles(SCPNs)can be generated at high polymer concentrations.Therefore,cyclic polymers with high purity can be constructed efficiently.This method overcomes the limitation of traditional ring-closure method,which is typically conducted in highly dilute conditions,providing an efficient method for the scalable preparation of cyclic polymers.展开更多
A rhodium(Ⅲ)-catalyzed hydrosilylation/cyclization reaction of cyclohexadienone-tetheredα,β-unsaturated aldehydes(1,6-dienes)with triethylsilane is described,providing a series of cishydrobenzofurans,cis-hydroindol...A rhodium(Ⅲ)-catalyzed hydrosilylation/cyclization reaction of cyclohexadienone-tetheredα,β-unsaturated aldehydes(1,6-dienes)with triethylsilane is described,providing a series of cishydrobenzofurans,cis-hydroindoles,and cishydroindenes bearing silyl enol ether in good to excellent yields and excellent stereoselectivities.Additionally,the versatility of this method was demonstrated through a gram-scale experiment and various downstream transformations,highlighting its utility.展开更多
3-Sulfenylindoles are widely found in natural products,bioactive molecules and organic functional materials.BF_(3)·OEt_(2)mediated electrophilic cyclization reaction of 2-alkynylaniline with N-(arylthio)succinimi...3-Sulfenylindoles are widely found in natural products,bioactive molecules and organic functional materials.BF_(3)·OEt_(2)mediated electrophilic cyclization reaction of 2-alkynylaniline with N-(arylthio)succinimide was developed leading to the efficient synthesis of various biologically active 3-sulfenylindoles in moderate to high yields under very mild conditions.This protocol has the advantages of broad scope,functional group diversity,mild conditions and ease of operation.Moreover,gram-scale preparation portends the practical application.展开更多
An organophosphoric acid catalyzed[3+3]cyclization of 2-arylidene-indan-1,3-diones with enaminones has been established,which afforded a series of structurally diverse indenoquinolinedione derivatives in moderate to e...An organophosphoric acid catalyzed[3+3]cyclization of 2-arylidene-indan-1,3-diones with enaminones has been established,which afforded a series of structurally diverse indenoquinolinedione derivatives in moderate to excellent yields.This[3+3]cyclization has some advantages such as mild reaction conditions,readily available catalyst and wide substrate range.This work not only provides an efficient method for constructing biologically important 1,4-dihydropyridine motif,but also suggests a possible reaction pathway and activation mode,therefore enriching the research contents of organophosphoric acid catalysis and[3+3]cyclization reactions.展开更多
Zeolites of *BEA framework topology containing isomorphously substituted Lewis acidic metal centers catalyze the liquid-phase intramolecular Prins cyclization of citronellal with outstanding catalytic activity and (di...Zeolites of *BEA framework topology containing isomorphously substituted Lewis acidic metal centers catalyze the liquid-phase intramolecular Prins cyclization of citronellal with outstanding catalytic activity and (dia-)stereoselectivity to the commercially most valuable product, isopulegol (IPL). Effects of the metal-center identity and solvent type were occasionally noted, yet without systematic studies hitherto reported. Here, characteristic dependences of catalytic activities and stereoselectivities on solvent and metal identity were uncovered over four M(IV)-Beta catalysts (M = Sn, Ti, Zr and Hf) in four distinct solvents (i.e., acetonitrile, tert-butanol, cyclohexane and n-hexane). Zr^(-) and Hf-Beta were the most active in acetonitrile and the most selective (> 90% to IPL) in tert-butanol, though their activities were generally lower than Ti- and Sn-Beta in solvents other than acetonitrile. By comparison, Ti-Beta was inferior to other catalysts in terms of both activity and IPL selectivity (as previously shown) in acetonitrile but became the most active in other solvents, with markedly increased IPL selectivity from 60% to 70%?80%. Combining multiple site discrimination and quantification techniques, turnover frequencies were determined for the first time in this reaction;such site-based activities, coupled with comprehensive kinetic interrogations, not only enabled a rigorous comparison of catalytic activities across M-Beta catalysts but also provided deeper insights into the free energy driving forces as solvent and metal identity are varied. The activity and selectivity trends, as well as those for the adsorption and intrinsic activation parameters are caused by solvent co-binding at the active site (acetonitrile and tert-butanol) and less quantifiable crowding effects (cyclohexane) due to the limited pore space and the need to accommodate relatively bulky reactant-derived moieties. This work exemplifies how the interplay of metal identity and solvent determines the reactivities and selectivities in Lewis-acid-catalyzed reactions within confined spaces.展开更多
Stereoselective functionalization at C-2 and C-3 of the gibberellin skeleton was achieved via an intramolecular free radical cyclization approach using a tethered C-19 halomethyl ester as the radical precursor.
A new gold self-relay catalytic annulation/nucleophilic substitution cascade of 1,3-enyne acetates with cyclic ether acetals is reported,enabling highly diastereoselective access to cyclic etherified cyclopentenones w...A new gold self-relay catalytic annulation/nucleophilic substitution cascade of 1,3-enyne acetates with cyclic ether acetals is reported,enabling highly diastereoselective access to cyclic etherified cyclopentenones with cyclic quaternary centers in moderate to good yields and>19∶1 dr.This catalysis enables the direct construction of two types of carboncyclic skeletons by adjusting the olefin types of 1,3-enyne acetates.When 1,3-enyne acetates bearing a cyclic alkene unit were used,5~6 fused bicarbocyclic products were diastereoselectively synthesized,whereas the reaction of acyclic 1,3-enyne acetates resulted in five-memebered carbocyclic framework.Notably,cyclic ether acetals are commonly used as protecting groups in traditional multistep organic syntheses,and in this reaction,such reagents serve as electrophilic cyclic ether precursors,achieving new uses for old reagents.The current method demonstrates good functional group compatibility,a broad substrate scope and high diastereoselectivity,providing a new synthetic strategy toward functionalized cyclopentenones.展开更多
文摘Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.
文摘Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.
基金supported by the National Natural Science Foundation of China(Nos.81725021,81903461)the National Key R&D Program of China(No.2022YFA1503200)the Natural Science Foundation of Hubei Province(No.ZRMS2023000340)。
文摘Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficiently accomplished from the key intermediate(S)-6 with three contiguous stereocenters in 5 steps and the synthetic 1 induced G2/M-phase cell cycle arrest of HT29 cells and apoptosis of HL60 and NB4 cells by activation of caspase-3 and degradation of PARP.(S)-6,bearing three contiguous chiral centers,was efficiently constructed by a novel Nazarov cyclization reaction containing basic nitrogen,which was less developed,primarily due to the incompatibility of basic nitrogen under acidic reaction conditions.This reaction allows a wide range of pentadienone substrates containing basic nitrogen to undergo Nazarov cyclization in a single regioselective and diastereoselective manner and is capable of generating three stereocenters simultaneously.Furthermore,the mechanism of the Nazarov cyclization and the origin of the regio-and diastereoselectivity were elucidated by DFT calculations and deuteration experiments,providing valuable insights into the reaction and serving as a guide for future applications involving substrates containing basic nitrogen.
基金financial support from the National Natural Science Foundation of China(Nos.22125108,22101238,22331004 and 22121001)Yunnan Fundamental Research Project(No.202401CF070024)+2 种基金Natural Science Foundation of Jiangsu Province(No.BK20211059)the Project of Science and Technology of Xuzhou Government(No.KC22080)NFFTBS(No.J1310024)。
文摘The Meinwald rearrangement has proven to be one of the most useful tools in organic synthesis.However,examples of asymmetric Meinwald rearrangements are quite scarce,and these reactions have so far been limited to the use of chiral Br?nsted acids as catalysts.Here,we report a copper-catalyzed asymmetric cascade cyclization/Meinwald rearrangement reaction,allowing the practical and atom-economic synthesis of a range of chiral tricyclic pyrroles bearing a chiral oxa-quaternary carbon stereocenter in high yields and enantioselectivities.Thus,this protocol not only represents the first transition-metal-catalyzed enantioselective Meinwald rearrangement,but also constitutes the first example of asymmetric formal monocarbon insertion into C-O bond of ester.Moreover,theoretical calculations provide further evidence for this multiple cascade cyclization and elucidate the origin of enantioselectivity.
基金the National Natural Science Foundation of China(Nos.22071066,22071065)the National Key Research and Development Program of China(No.2016YFA0602900)+1 种基金the Guangdong Natural Science Foundation,China(No.2018B030311008)the Guangzhou Science and Technology Project,China(No.202102020802).
文摘Early diagnosis and treatment of cancer requires the development of tools that are both sensitive and selective in detecting spermine.In this study,we presented a"supramolecular cyclization-induced emission enhancement"strategy for the sensitive and selective detection of spermine.A new pillar[5]arene probe(P1)demonstrated excellent solution/solid dual-state emission properties,and the addition of certain spermine(Spm)resulted in fluorescence enhancement due to the synergy of multiple weak interactions that restricted the free motion of P1 in the P1⊃Spm complex.This mechanism was further confirmed by time-resolved spectroscopy,DFT calculations,and IGM analysis.With its low limit of detection and high selectivity,P1 is a promising tool for measuring spermine in artificial urine samples.
基金The financial support from the National Natural Science Foundation of China(Nos.22201276,22131010,52021002)the Fundamental Research Funds for the Central Universities(No.WK2060000012)is gratefully acknowledged.
文摘Cyclic polymers are a class of polymers that feature endless topology,and the synthesis of cyclic polymers has attracted the attention of many researchers.Herein,cyclic polymers were efficiently constructed by self-folding cyclization technique at high concentrations.Linear poly((oligo(ethylene glycol)acrylate)-co-(dodecyl acrylate))(P(OEGA-co-DDA))precursors with different ratios of hydrophilic and hydrophobic moieties were synthesized by reversible addition-fragmentation chain transfer(RAFT)polymerization using a bifunctional chain transfer agent with two anthryl end groups.The amphiphilic linear precursors underwent the self-folding process to generate polymeric nanoparticles in water.By irradiating the aqueous solution of the nanoparticles with 365 nm UV light,cyclic polymers were synthesized successfully via coupling of anthryl groups.The effects of the ratios of hydrophilic and hydrophobic moieties in linear P(OEGA-co-DDA)copolymers and polymer concentration on the purity of the obtained cyclic polymers were explored in detail via ^(1)H nuclear magnetic resonance(^(1)H NMR),dynamic light scattering(DLS),UV‒visible(vis)analysis,three-detection size exclusion chromatography(TD-SEC)and transmission electron microscopy(TEM).It was found that by adjusting the content of the hydrophilic segments in linear precursors,single chain polymeric nanoparticles(SCPNs)can be generated at high polymer concentrations.Therefore,cyclic polymers with high purity can be constructed efficiently.This method overcomes the limitation of traditional ring-closure method,which is typically conducted in highly dilute conditions,providing an efficient method for the scalable preparation of cyclic polymers.
基金financial support from the National Key R&D Program of China(No.2022YFF1202600)the National Natural Science Foundation of China(Nos.22001172,22071155,and22371188)+4 种基金the Science and Technology Commission of Shanghai Municipality(Nos.20XD1403600 and 20400750300)the Shanghai Municipal Education Commission(No.2019-01-07-00-10-E00072)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-202004)the Shanghai Municipal Health Commission/Shanghai Municipal Administration of Traditional Chinese Medicine[No.ZY(2021-2023)-0501]Organizational Key R&D Program of SHUTCM(No.2023YZZ01)。
文摘A rhodium(Ⅲ)-catalyzed hydrosilylation/cyclization reaction of cyclohexadienone-tetheredα,β-unsaturated aldehydes(1,6-dienes)with triethylsilane is described,providing a series of cishydrobenzofurans,cis-hydroindoles,and cishydroindenes bearing silyl enol ether in good to excellent yields and excellent stereoselectivities.Additionally,the versatility of this method was demonstrated through a gram-scale experiment and various downstream transformations,highlighting its utility.
文摘3-Sulfenylindoles are widely found in natural products,bioactive molecules and organic functional materials.BF_(3)·OEt_(2)mediated electrophilic cyclization reaction of 2-alkynylaniline with N-(arylthio)succinimide was developed leading to the efficient synthesis of various biologically active 3-sulfenylindoles in moderate to high yields under very mild conditions.This protocol has the advantages of broad scope,functional group diversity,mild conditions and ease of operation.Moreover,gram-scale preparation portends the practical application.
文摘An organophosphoric acid catalyzed[3+3]cyclization of 2-arylidene-indan-1,3-diones with enaminones has been established,which afforded a series of structurally diverse indenoquinolinedione derivatives in moderate to excellent yields.This[3+3]cyclization has some advantages such as mild reaction conditions,readily available catalyst and wide substrate range.This work not only provides an efficient method for constructing biologically important 1,4-dihydropyridine motif,but also suggests a possible reaction pathway and activation mode,therefore enriching the research contents of organophosphoric acid catalysis and[3+3]cyclization reactions.
文摘Zeolites of *BEA framework topology containing isomorphously substituted Lewis acidic metal centers catalyze the liquid-phase intramolecular Prins cyclization of citronellal with outstanding catalytic activity and (dia-)stereoselectivity to the commercially most valuable product, isopulegol (IPL). Effects of the metal-center identity and solvent type were occasionally noted, yet without systematic studies hitherto reported. Here, characteristic dependences of catalytic activities and stereoselectivities on solvent and metal identity were uncovered over four M(IV)-Beta catalysts (M = Sn, Ti, Zr and Hf) in four distinct solvents (i.e., acetonitrile, tert-butanol, cyclohexane and n-hexane). Zr^(-) and Hf-Beta were the most active in acetonitrile and the most selective (> 90% to IPL) in tert-butanol, though their activities were generally lower than Ti- and Sn-Beta in solvents other than acetonitrile. By comparison, Ti-Beta was inferior to other catalysts in terms of both activity and IPL selectivity (as previously shown) in acetonitrile but became the most active in other solvents, with markedly increased IPL selectivity from 60% to 70%?80%. Combining multiple site discrimination and quantification techniques, turnover frequencies were determined for the first time in this reaction;such site-based activities, coupled with comprehensive kinetic interrogations, not only enabled a rigorous comparison of catalytic activities across M-Beta catalysts but also provided deeper insights into the free energy driving forces as solvent and metal identity are varied. The activity and selectivity trends, as well as those for the adsorption and intrinsic activation parameters are caused by solvent co-binding at the active site (acetonitrile and tert-butanol) and less quantifiable crowding effects (cyclohexane) due to the limited pore space and the need to accommodate relatively bulky reactant-derived moieties. This work exemplifies how the interplay of metal identity and solvent determines the reactivities and selectivities in Lewis-acid-catalyzed reactions within confined spaces.
文摘Stereoselective functionalization at C-2 and C-3 of the gibberellin skeleton was achieved via an intramolecular free radical cyclization approach using a tethered C-19 halomethyl ester as the radical precursor.
文摘A new gold self-relay catalytic annulation/nucleophilic substitution cascade of 1,3-enyne acetates with cyclic ether acetals is reported,enabling highly diastereoselective access to cyclic etherified cyclopentenones with cyclic quaternary centers in moderate to good yields and>19∶1 dr.This catalysis enables the direct construction of two types of carboncyclic skeletons by adjusting the olefin types of 1,3-enyne acetates.When 1,3-enyne acetates bearing a cyclic alkene unit were used,5~6 fused bicarbocyclic products were diastereoselectively synthesized,whereas the reaction of acyclic 1,3-enyne acetates resulted in five-memebered carbocyclic framework.Notably,cyclic ether acetals are commonly used as protecting groups in traditional multistep organic syntheses,and in this reaction,such reagents serve as electrophilic cyclic ether precursors,achieving new uses for old reagents.The current method demonstrates good functional group compatibility,a broad substrate scope and high diastereoselectivity,providing a new synthetic strategy toward functionalized cyclopentenones.
