The Ni-Al bimetallic catalysis of intramolecular enantioselective and regioselective C-H cyclization of4-oxoquinazolines with tethered alkenes has been successfully developed.Some new secondary phosphine oxides(SPOs)w...The Ni-Al bimetallic catalysis of intramolecular enantioselective and regioselective C-H cyclization of4-oxoquinazolines with tethered alkenes has been successfully developed.Some new secondary phosphine oxides(SPOs)with large steric hindrance(SPO6-11)were designed and successfully synthesized from readily available chiral amines or amino acids.The developed chiral SPOs as ligands or preligands demonstrate much higher efficiency in the asymmetric catalytic reactions than the reported traditional ones.A new class of chiral tricyclic pyrroloquinazolinones were obtained in up to 95%yield and 99%ee.展开更多
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
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
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
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 development of enantioselective C-H macrocyclizations to efficiently access structurally diversified macrocycles is highly desirable,but remain a big challenge.Herein,we reported the first rhodium(Ⅲ)-catalyzed as...The development of enantioselective C-H macrocyclizations to efficiently access structurally diversified macrocycles is highly desirable,but remain a big challenge.Herein,we reported the first rhodium(Ⅲ)-catalyzed asymmetric intramolecular C-H macrocyclization,enabling the efficient synthesis of structurally diverse enantioenriched macrocycles.This robust enantioselective C-H macrocyclization has a broad functional group tolerance,excellent enantioselectivities(up to 98.5:1.5 e.r.)and a mild reaction condition,releasing CO_(2)as the single by-product.More significantly,the resulting unique enantioenriched19-membered macrocycle 2f was found to demonstrate a potent in vitro anti-Zika virus(ZIKV)activity without obvious cytotoxicity.Further investigation revealed that the anti-ZIKV activity is presumably attributed to an autophagy inhibition in the early stage of viral infection by down-regulating the expression of autophagy related gene Atg12.展开更多
Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face wit...Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face with their intrinsic limitations including metabolic instability and low membrane permeability,the strategies for synthesizing unnatural amino acids and peptides are explored.Among the methods for modifying amino acids and peptides,chemo-and site-selective approaches are preferred because of the ability to fine-tuning structural features.Recently,transition metal-catalyzed Csingle bondH activation has been employed for the functionalization of amino acids and peptides.Through domino Csingle bondH activation/annulation,a series of structurally complex and diverse amino acids and peptides is constructed.This review highlights recent advances in the synthesis of unnatural amino acids and peptides via transition metal-catalyzed Csingle bondH activation/annulation.展开更多
In this study,electrochemical C-H carboxylation of benzylamines with CO_(2) was reported.This linear paired electrolysis system enables efficient and economical synthesis of value-added α-amino acids(α-AAs) under mi...In this study,electrochemical C-H carboxylation of benzylamines with CO_(2) was reported.This linear paired electrolysis system enables efficient and economical synthesis of value-added α-amino acids(α-AAs) under mild conditions.Various substituted benzylamines containing diverse functional groups and even highly reactive moieties,such as cyano,amide and alkene groups could be successfully transformed to the carboxylated products.Notably,this method proved to be applicable to the late-stage modification of biorelevant compounds,highlighting its potential for synthetic chemistry.Mechanistic studies such as radical trapping experiments,kinetic isotope effect(KIE) tests and cyclic voltammetry(CV) studies provided useful insight into this transformation.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
A highly efficient and selective[2+2+2]cyclization of diynes and monoalkynes was catalyzed by rhodium under room temperature in water/THF mixed solvent,affording isoindolines and isobenzofurans in good to excellent yi...A highly efficient and selective[2+2+2]cyclization of diynes and monoalkynes was catalyzed by rhodium under room temperature in water/THF mixed solvent,affording isoindolines and isobenzofurans in good to excellent yields.The center atoms (N,O) in the diynes showed a significant effect for the cyclization.展开更多
Cyclopeptidomimetics are class of cyclopeptides with unnatural linkage. They usually displayed unique constrained structure, enhanced proteolytic stability, and other drug-like character; and have been widely used in ...Cyclopeptidomimetics are class of cyclopeptides with unnatural linkage. They usually displayed unique constrained structure, enhanced proteolytic stability, and other drug-like character; and have been widely used in medicinal chemistry. Therefore, development of efficient strategies for the synthesis of cyclopeptidomimetics has received many attentions. On-resin cyclization strategy is one of the effective approaches developed to overcome the competing side reaction such as oligomerization and cyclooligomers occurred in solution cyclization. This approach took advantage of the ＂pseudo-dilution＂ effect to avoid these undesired by-products and greatly simplified the downstream product purification process. This review summarized the recent on-resin peptide cyclization strategies for the synthesis of cvclooeotidomimetics.展开更多
Rhodium(Ⅲ)-catalyzed synthesis of indole derivatives has been realized via cascade reaction of C -H alkylation/nucleophilic cyclization starting from readily available N-phenylpyridin-2-amines and sulfoxonium ylides....Rhodium(Ⅲ)-catalyzed synthesis of indole derivatives has been realized via cascade reaction of C -H alkylation/nucleophilic cyclization starting from readily available N-phenylpyridin-2-amines and sulfoxonium ylides. Notably, this transformation could smoothly proceed with high yields, good regioselectivity, and feature broad group tolerance and under redox-neutral condition to avoid external oxidant. The titled products are potentially important building blocks in the organic synthesis through various chemical transformations.展开更多
1-[1-（Benzyloxy）-3-methylnaphthalen-4-yloxy]propan-2-one （la） took place a cyclization, debenzylation and oxidation to form 9-substitued benzo[de]chromene-7,8-dione （2a） and 5-benzyl-9-substitued benzo[de]chrome...1-[1-（Benzyloxy）-3-methylnaphthalen-4-yloxy]propan-2-one （la） took place a cyclization, debenzylation and oxidation to form 9-substitued benzo[de]chromene-7,8-dione （2a） and 5-benzyl-9-substitued benzo[de]chromene-7,8-dione （3a）. The mechanisms for these reactions were discussed.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 highly stereoselective asymmetric cascade cyclization reaction between o-hydroxycinnamaldehydes and diphenylphosphine oxide has been achieved with 84%-99% ee and 7：1-20：1 dr under the catalysis of L-diarylprolinol...A highly stereoselective asymmetric cascade cyclization reaction between o-hydroxycinnamaldehydes and diphenylphosphine oxide has been achieved with 84%-99% ee and 7：1-20：1 dr under the catalysis of L-diarylprolinol silyl ether. This reaction provides a facile access to highly enantioenriched 4- diphenylphosphinyl chroman-2-ols. It also represents a novel organocatalytic asymmetric phospha- Michael addition of α,β-unsaturated aldehydes with pentavalent P-nucleophiles.展开更多
基金the National Natural Science Foundation of China(No.22071270)Science and Technology Program of Guangzhou(20220602JBGS02)+1 种基金Guangdong Province Zhu Jiang Talents Plan(No.2016ZT06C090)Guangzhou City Talents Plan(No.CYLJTD201609)for financial support。
文摘The Ni-Al bimetallic catalysis of intramolecular enantioselective and regioselective C-H cyclization of4-oxoquinazolines with tethered alkenes has been successfully developed.Some new secondary phosphine oxides(SPOs)with large steric hindrance(SPO6-11)were designed and successfully synthesized from readily available chiral amines or amino acids.The developed chiral SPOs as ligands or preligands demonstrate much higher efficiency in the asymmetric catalytic reactions than the reported traditional ones.A new class of chiral tricyclic pyrroloquinazolinones were obtained in up to 95%yield and 99%ee.
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.
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supported by National Natural Science Foundation of China(No.81973166)Science and Technology Commission of Shanghai Municipality(No.22XD1424600)+4 种基金Natural Science Foundation of Shanghai Municipality(No.22ZR1474100)Taishan Scholar Foundation of Shandong Province(No.tsqn202306322)National Key R&D Program of China(No.2021YFC2300700)Shandong Laboratory Program(No.SYS202205)Shandong Provincial Natural Science Foundation(Nos.ZR2023LSW003 and ZR2023JQ028)。
文摘The development of enantioselective C-H macrocyclizations to efficiently access structurally diversified macrocycles is highly desirable,but remain a big challenge.Herein,we reported the first rhodium(Ⅲ)-catalyzed asymmetric intramolecular C-H macrocyclization,enabling the efficient synthesis of structurally diverse enantioenriched macrocycles.This robust enantioselective C-H macrocyclization has a broad functional group tolerance,excellent enantioselectivities(up to 98.5:1.5 e.r.)and a mild reaction condition,releasing CO_(2)as the single by-product.More significantly,the resulting unique enantioenriched19-membered macrocycle 2f was found to demonstrate a potent in vitro anti-Zika virus(ZIKV)activity without obvious cytotoxicity.Further investigation revealed that the anti-ZIKV activity is presumably attributed to an autophagy inhibition in the early stage of viral infection by down-regulating the expression of autophagy related gene Atg12.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK20220409)the National Natural Science Foundation of China(No.22401153)+2 种基金the FWO[Fund for Scientific Research-Flanders(Belgium)]for financial support(recipient Erik V.Van der Eycken)the Research Council of the KU Leuven(recipient Erik V.Van der Eycken)the support of the"RUDN University Strategic Academic Leadership Program"(recipient Erik V.Van der Eycken).
文摘Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face with their intrinsic limitations including metabolic instability and low membrane permeability,the strategies for synthesizing unnatural amino acids and peptides are explored.Among the methods for modifying amino acids and peptides,chemo-and site-selective approaches are preferred because of the ability to fine-tuning structural features.Recently,transition metal-catalyzed Csingle bondH activation has been employed for the functionalization of amino acids and peptides.Through domino Csingle bondH activation/annulation,a series of structurally complex and diverse amino acids and peptides is constructed.This review highlights recent advances in the synthesis of unnatural amino acids and peptides via transition metal-catalyzed Csingle bondH activation/annulation.
基金Financial support from National Key R&D Program of China (No.2023YFA1507203)National Natural Science Foundation of China (Nos.22371149 and 22188101)+3 种基金the Fundamental Research Funds for the Central Universities (No.63224098)Frontiers Science Center for New Organic Matter,Nankai University (No.63181206)Nankai University are gratefully acknowledgedthe Haihe Laboratory of Sustainable Chemical Transformations for financial support。
文摘In this study,electrochemical C-H carboxylation of benzylamines with CO_(2) was reported.This linear paired electrolysis system enables efficient and economical synthesis of value-added α-amino acids(α-AAs) under mild conditions.Various substituted benzylamines containing diverse functional groups and even highly reactive moieties,such as cyano,amide and alkene groups could be successfully transformed to the carboxylated products.Notably,this method proved to be applicable to the late-stage modification of biorelevant compounds,highlighting its potential for synthetic chemistry.Mechanistic studies such as radical trapping experiments,kinetic isotope effect(KIE) tests and cyclic voltammetry(CV) studies provided useful insight into this transformation.
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...
文摘A highly efficient and selective[2+2+2]cyclization of diynes and monoalkynes was catalyzed by rhodium under room temperature in water/THF mixed solvent,affording isoindolines and isobenzofurans in good to excellent yields.The center atoms (N,O) in the diynes showed a significant effect for the cyclization.
基金supported by the National Natural Science Foundation of China (No.21472070)the Project for Jiangsu Scientific and Technological Innovation Team+1 种基金Fund for Jiangsu Distinguished Professorship ProgramProject Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,the 111 Project (No.111-2-06)
文摘Cyclopeptidomimetics are class of cyclopeptides with unnatural linkage. They usually displayed unique constrained structure, enhanced proteolytic stability, and other drug-like character; and have been widely used in medicinal chemistry. Therefore, development of efficient strategies for the synthesis of cyclopeptidomimetics has received many attentions. On-resin cyclization strategy is one of the effective approaches developed to overcome the competing side reaction such as oligomerization and cyclooligomers occurred in solution cyclization. This approach took advantage of the ＂pseudo-dilution＂ effect to avoid these undesired by-products and greatly simplified the downstream product purification process. This review summarized the recent on-resin peptide cyclization strategies for the synthesis of cvclooeotidomimetics.
基金partial financial support from the Ministry of Science and Technology of China (No. 2016YFE0132600)Zhengzhou University
文摘Rhodium(Ⅲ)-catalyzed synthesis of indole derivatives has been realized via cascade reaction of C -H alkylation/nucleophilic cyclization starting from readily available N-phenylpyridin-2-amines and sulfoxonium ylides. Notably, this transformation could smoothly proceed with high yields, good regioselectivity, and feature broad group tolerance and under redox-neutral condition to avoid external oxidant. The titled products are potentially important building blocks in the organic synthesis through various chemical transformations.
基金We are indebted to the National Natural Science Foundation of China （No.20272085,20472117）the Guangzhou City Science Foundation,the Guangdong Provincial Science Foundation（031594）the Scientific Research Foundation for the Returned 0verseas Chinese Scholars,and the HongKong Polytechnic University Area of Strategic Development Fund for financial support of this study.
文摘1-[1-（Benzyloxy）-3-methylnaphthalen-4-yloxy]propan-2-one （la） took place a cyclization, debenzylation and oxidation to form 9-substitued benzo[de]chromene-7,8-dione （2a） and 5-benzyl-9-substitued benzo[de]chromene-7,8-dione （3a）. The mechanisms for these reactions were discussed.
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Financial support from the National Natural Science Foundation of China(Nos. 21472096, J1103306)
文摘A highly stereoselective asymmetric cascade cyclization reaction between o-hydroxycinnamaldehydes and diphenylphosphine oxide has been achieved with 84%-99% ee and 7：1-20：1 dr under the catalysis of L-diarylprolinol silyl ether. This reaction provides a facile access to highly enantioenriched 4- diphenylphosphinyl chroman-2-ols. It also represents a novel organocatalytic asymmetric phospha- Michael addition of α,β-unsaturated aldehydes with pentavalent P-nucleophiles.
