A visible-light induced cascade sulfonation/cyclization reaction of 3-allyl-2-arylquinazolinones employing water as an environmentally friendly solvent was revealed.This transition metal-free protocol,using 9-mesityl-...A visible-light induced cascade sulfonation/cyclization reaction of 3-allyl-2-arylquinazolinones employing water as an environmentally friendly solvent was revealed.This transition metal-free protocol,using 9-mesityl-10-methylacridinium perchlorate as the photocatalyst,represents a masterly tactic for the synthesis of sulfonated dihydroisoquinolino[1,2-b]quinazolinones featuring mild conditions,facile operation,and broad substrate scope.展开更多
Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation inv...Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation involve either C6-C10 cyclization(path a) or C2-C10 cyclization(path b) after the C10carbocation formation,but neither has been experimentally validated.Here,we have identified a second mangicdiene synthase Man D,which is derived from Fusarium sp.JNU-XJ070152-01 and shares high amino acid sequence identity with Fg MS.Through heterologous expression of man D in Aspergillus oryzae NSAR1,we observed production not only of mangicdiene(1) and variecoltetraene(2),previously identified by expression of Fg MS in Escherichia coli,but also two novel sesterterpene skeletons fusadiene(3)and fusatriene(4).The identification of fusadiene and fusatriene supports the occurrence of two key carbocation intermediates in path b,thus experimentally confirming that mangicdiene is built via path b for the first time,consistent with previous density functional theory(DFT) calculation results.展开更多
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
N-(2-Ethynylphenyl)acrylamides have emerged as key intermediates for the synthesis of complex heteropolycyclic compounds.The recent advances focus on the tandem cyclization involving these precursors,among which forma...N-(2-Ethynylphenyl)acrylamides have emerged as key intermediates for the synthesis of complex heteropolycyclic compounds.The recent advances focus on the tandem cyclization involving these precursors,among which formation of fused six/N-three,six/five(N,S,O),and six/six-membered rings are highlighted.Nitrogen,sulfur,and oxygen incorporations into five-membered rings provide efficient routes to bioactive polycyclic molecules.These cyclization reactions exhibit excellent atom economy,high efficiency,and good functional group compatibility.Furthermore,novel catalytic systems and photochemical strategies also expand the synthetic applications of these precursors.Taken together,these advancements offer versatile tools for the synthesis of intricate heterocyclic scaffolds with broad applications in organic and medicinal chemistry.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
Intramolecular end-to-end reactions of long-chain linear precursors remain challenging due to their inherent tendency to undergo intermolecular reactions.Herein,we investigated the cascade hydrolysis and intramolecula...Intramolecular end-to-end reactions of long-chain linear precursors remain challenging due to their inherent tendency to undergo intermolecular reactions.Herein,we investigated the cascade hydrolysis and intramolecular cyclization reactions of three vips with varying lengths within the well-defined nanocavities of cavitands in aqueous solution.Driven by hydrophobic effect,these vips were encapsulated within the dimeric capsules,adopting distinct conformations and orientations due to spatial constraints.Specifically,the shorter vip maintained an extended linear geometry,whereas the longer vips adopted a folded binding mode.Upon initiating the reaction,the terminal residue of the shorter vip displayed lower reactivity,while the longer vips,preorganized within the cavity,underwent efficient cyclization,resulting in significant differences in reaction kinetics.Furthermore,electrostatic potential fields played a critical role in modulating reaction rates,with the positively charged cavitand accelerating the reaction more efficiently compared to its negatively charged counterpart,likely due to stabilization of the anionic transition state.This study provides an effective strategy for designing enzymemimetic nanoreactors through the utilization of well-defined nanospaces.展开更多
The controlled incorporation of heptagons into helicene frameworks offers a promising approach to modulate their structural and electronic properties.This study demonstrates the synthesis of two heptagonembedded oxa-h...The controlled incorporation of heptagons into helicene frameworks offers a promising approach to modulate their structural and electronic properties.This study demonstrates the synthesis of two heptagonembedded oxa-helicenes:one with a single heptagon(5)and another with two heptagons(6),achieved through controlled oxidative cyclization of a triple oxa-helicene(4).UV-vis absorption and emission spectra revealed red-shifts and slight increases in Stokes shifts from 4 to 6,attributed toπ-system extension and greater structural relaxation in the excited state.5 and 6 exhibited fluorescence quantum yields 2-3times higher than 4.Chiral separation and thermal stability analyses showed a significant decrease in enantiomeric stability for 5 and 6 compared to 4,due to planarization effects induced by heptagon incorporation.The chiroptical properties were also investigated,revealing reduced optical dissymmetry factors after heptagon embedding.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
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 novel macrolactonization method was developed using a chiral β-lactam as the template. This novel method features that the macrocyclization is simultaneously achieved while a TBS protected hydroxy group is deprotec...A novel macrolactonization method was developed using a chiral β-lactam as the template. This novel method features that the macrocyclization is simultaneously achieved while a TBS protected hydroxy group is deprotected.展开更多
The Lewis acid mediated polystyrene supported selenium cyclization of chalcones and oxidative cleavage of selenium resins flavonoids in good yields and purities have been reported. induced intramolecular gave the cor...The Lewis acid mediated polystyrene supported selenium cyclization of chalcones and oxidative cleavage of selenium resins flavonoids in good yields and purities have been reported. induced intramolecular gave the corresponding展开更多
A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The l...A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC,50%(v/v) DMF/H_2O was employed as the solvent to overcome the difficulty of solubilization...展开更多
基金funds from Natural Science Foundation of Guangxi Province(Nos.2023GXNSFBA026304,2023GXNSFDA026063)the Guangxi Science and Technology Base and Special Talents(No.Guike AD20159047).
文摘A visible-light induced cascade sulfonation/cyclization reaction of 3-allyl-2-arylquinazolinones employing water as an environmentally friendly solvent was revealed.This transition metal-free protocol,using 9-mesityl-10-methylacridinium perchlorate as the photocatalyst,represents a masterly tactic for the synthesis of sulfonated dihydroisoquinolino[1,2-b]quinazolinones featuring mild conditions,facile operation,and broad substrate scope.
基金financially supported by grants from the National Key Research and Development Program of China (No.2024YFE0102000)the National Natural Science Foundation of China (Nos.81925037,82321004,U22A20371,U24A20782,32170060,22177037,22207039,22307045)+6 种基金the Guangdong Major Project of Basic and Applied Basic Research (No.2023B0303000026)the Guangdong Natural Science Funds for Distinguished Young Scholars (No.2022B1515020028,China)the Guangdong International Science and Technology Cooperation Base (No.2021A0505020015,China)the Guangdong Basic and Applied Basic Research Foundation (Nos.2023B1515040016,2023A1515110388)the Innovative and Research Teams Project of Guangdong Higher Education Institution (No.2021KCXTD001,China)the Guangzhou Science and Technology Project (Nos.202206010020,2024A04J6241,2023A04J0080,China)the Fundamental Research Funds for the Central Universities (Nos.21623105,21624210)。
文摘Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation involve either C6-C10 cyclization(path a) or C2-C10 cyclization(path b) after the C10carbocation formation,but neither has been experimentally validated.Here,we have identified a second mangicdiene synthase Man D,which is derived from Fusarium sp.JNU-XJ070152-01 and shares high amino acid sequence identity with Fg MS.Through heterologous expression of man D in Aspergillus oryzae NSAR1,we observed production not only of mangicdiene(1) and variecoltetraene(2),previously identified by expression of Fg MS in Escherichia coli,but also two novel sesterterpene skeletons fusadiene(3)and fusatriene(4).The identification of fusadiene and fusatriene supports the occurrence of two key carbocation intermediates in path b,thus experimentally confirming that mangicdiene is built via path b for the first time,consistent with previous density functional theory(DFT) calculation results.
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.
基金Project supported by the Special Fund Project for Scientific Research Openness of the Key Laboratory of Medical Conditioning Functional Food Processing Technology in Weihai City(No.WHYY20240006)the Mid-Young Teachers Visiting Program of Qingdao Agricultural University(No.2024)+1 种基金the General Education Reform and Research Project of Qingdao Agricultural University(No.XJY2024063)the Research Results of the Ideological and Political Education Research Project of Qingdao Agricultural University(No:QNSZ2025023)。
文摘N-(2-Ethynylphenyl)acrylamides have emerged as key intermediates for the synthesis of complex heteropolycyclic compounds.The recent advances focus on the tandem cyclization involving these precursors,among which formation of fused six/N-three,six/five(N,S,O),and six/six-membered rings are highlighted.Nitrogen,sulfur,and oxygen incorporations into five-membered rings provide efficient routes to bioactive polycyclic molecules.These cyclization reactions exhibit excellent atom economy,high efficiency,and good functional group compatibility.Furthermore,novel catalytic systems and photochemical strategies also expand the synthetic applications of these precursors.Taken together,these advancements offer versatile tools for the synthesis of intricate heterocyclic scaffolds with broad applications in organic and medicinal chemistry.
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funded by the National Natural Science Foundation of China(Nos.22271154,M-0411)the China Postdoctoral Science Foundation(No.2023M731658)+2 种基金the Science Fund for Distinguished Young Scholars of Jiangsu Province(No.BK20240078)the Innovation Support Program of Jiangsu Province(No.BZ2023055)the High-Performance Computing Platform of Peking Uniersity。
文摘Intramolecular end-to-end reactions of long-chain linear precursors remain challenging due to their inherent tendency to undergo intermolecular reactions.Herein,we investigated the cascade hydrolysis and intramolecular cyclization reactions of three vips with varying lengths within the well-defined nanocavities of cavitands in aqueous solution.Driven by hydrophobic effect,these vips were encapsulated within the dimeric capsules,adopting distinct conformations and orientations due to spatial constraints.Specifically,the shorter vip maintained an extended linear geometry,whereas the longer vips adopted a folded binding mode.Upon initiating the reaction,the terminal residue of the shorter vip displayed lower reactivity,while the longer vips,preorganized within the cavity,underwent efficient cyclization,resulting in significant differences in reaction kinetics.Furthermore,electrostatic potential fields played a critical role in modulating reaction rates,with the positively charged cavitand accelerating the reaction more efficiently compared to its negatively charged counterpart,likely due to stabilization of the anionic transition state.This study provides an effective strategy for designing enzymemimetic nanoreactors through the utilization of well-defined nanospaces.
基金financially supported by the Ministry of Science and Technology of China(No.2017YFA0204902)the National Natural Science Foundation of China(Nos.21901217,22101241)。
文摘The controlled incorporation of heptagons into helicene frameworks offers a promising approach to modulate their structural and electronic properties.This study demonstrates the synthesis of two heptagonembedded oxa-helicenes:one with a single heptagon(5)and another with two heptagons(6),achieved through controlled oxidative cyclization of a triple oxa-helicene(4).UV-vis absorption and emission spectra revealed red-shifts and slight increases in Stokes shifts from 4 to 6,attributed toπ-system extension and greater structural relaxation in the excited state.5 and 6 exhibited fluorescence quantum yields 2-3times higher than 4.Chiral separation and thermal stability analyses showed a significant decrease in enantiomeric stability for 5 and 6 compared to 4,due to planarization effects induced by heptagon incorporation.The chiroptical properties were also investigated,revealing reduced optical dissymmetry factors after heptagon embedding.
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.
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.
基金This work is supported by the National Natural Science Foundation of China (grant No: 20372056)a Research Fund from the Royal Society of Chemistry. UK.
文摘A novel macrolactonization method was developed using a chiral β-lactam as the template. This novel method features that the macrocyclization is simultaneously achieved while a TBS protected hydroxy group is deprotected.
基金the National Natural Science Foundation of China （No. 20332050）
文摘The Lewis acid mediated polystyrene supported selenium cyclization of chalcones and oxidative cleavage of selenium resins flavonoids in good yields and purities have been reported. induced intramolecular gave the corresponding
基金supported by National Natural Science Foundation(No.30672546)Shanghai Municipal Committee of S & T(No.0652nm013)National Key Basic Research Program of China(No.2007CB935800)
文摘A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC,50%(v/v) DMF/H_2O was employed as the solvent to overcome the difficulty of solubilization...
