A novel synthesis of C2-spiroindoline derivatives based on the cascade reaction of 2-aryl-3H-indoles with cyclo- propanols is presented. The formation of product involves Rh(III)-catalyzed aryl C(sp2)—H bond alkylati...A novel synthesis of C2-spiroindoline derivatives based on the cascade reaction of 2-aryl-3H-indoles with cyclo- propanols is presented. The formation of product involves Rh(III)-catalyzed aryl C(sp2)—H bond alkylation of 2-aryl- 3H-indole, which is followed by intramolecular spiroannulation. In this tandem process, cyclopropanol acts as not only an alkylating agent but also a masked nucleophile to take part in the construction of the spirocyclic scaffold. Meanwhile, air acts as an economical and sustainable oxidant to promote the regeneration of the active catalyst. By using this method, hybrid compounds containing the central scaffolds of some clinical drugs were prepared effectively. In general, this newly developed method has advantages such as easily obtainable substrates, concise synthetic procedure, excellent atom-economy, good compatibility with diverse functional groups and ready scalability.展开更多
Wound healing in diabetic patients presents significant challenges due to heightened risks of bacterial infection,elevated glucose levels,and insufficient angiogenesis.Nanozymes are widely employed for wound healing,b...Wound healing in diabetic patients presents significant challenges due to heightened risks of bacterial infection,elevated glucose levels,and insufficient angiogenesis.Nanozymes are widely employed for wound healing,but most current nanozyme systems exhibit only moderate activity limited by incompatible reaction microenvironments including p H and hydrogen peroxide(H_(2)O_(2))concentration.Herein,a glucoseactivated nanozyme hydrogel was developed using bovine serum albumin(BSA)-modified gold nanoparticles(Au NPs)attached to a two-dimensional(2D)metal-organic framework(MOF)(Cu-TCPP(Fe)@Au@BSA)by an in situ growth method.The Au NPs function as a glucose oxidase(GOx)-like enzyme,converting glucose to gluconic acid and H_(2)O_(2),triggering the peroxidase(POD)-like activity of Cu-TCPP(Fe)to produce hydroxyl radicals(·OH),effectively eliminating bacteria.Additionally,the modification of BSA reduces the Au NP size,enhancing enzyme activity.Both in vitro and in vivo tests demonstrate that this nanozyme hydrogel can be activated by the microenvironment to lower blood glucose,eliminate bacterial infections,and promote epithelial formation and collagen deposition,thus accelerating diabetic wound healing effectively.The multifunctional nanozyme hydrogel dressing developed in this study presents a promising therapeutic approach to enhance diabetic wound healing.展开更多
A composite metal-organic frameworks(MOFs)structure,designated as Co-hmta@La-salen,was synthesized through coordination interactions between a one-dimensional lanthanum MOFs(La-salen)with high density of uncoordinated...A composite metal-organic frameworks(MOFs)structure,designated as Co-hmta@La-salen,was synthesized through coordination interactions between a one-dimensional lanthanum MOFs(La-salen)with high density of uncoordinated imine(-CH=N-)groups and a cobalt-based MOFs(Co-hmta)structure prepared using hydrogen bonding stacking with hexamethylenetetramine(hmta)as the organic ligand.Subsequently,the Co-hmta@La-salen composite was chosen as a template for the pyrolysis process to synthesize a La(OH)_(3)supported metallic Co catalyst incorporating carbon-nitrogen(Co/La(OH)_(3)-CNhmta)catalyst.The catalytic results show that Co/La(OH)_(3)-CN-hmta(54%and 46%selectivity for aniline and N-phenylbenzylamine,respectively)displays superior cascade performance compared to classic Co/La(OH)_(3)-CN-nit catalyst(69%and 31%selectivity for aniline and N-phenylbenzylamine,respectively).Moreover,the kinetic test results indicate that N-alkylation is the rate-limiting step of the overall cascade reaction.The Co/La(OH)_(3)-CN-hmta catalyst can be separated from the reaction system using a magnet,and it also exhibits good cyclic stability.All of these suggest that the“MOFs plus MOFs via coordination”templating method can be employed as an efficient strategy for the preparation of supported catalysts.展开更多
An efficient Cu catalyzed selective arylation/annulation cascade reaction of 2-alkynylanilines with diaryliodonium salts was developed.This reaction was selective to N-arylation instead of C-arylation,which provides a...An efficient Cu catalyzed selective arylation/annulation cascade reaction of 2-alkynylanilines with diaryliodonium salts was developed.This reaction was selective to N-arylation instead of C-arylation,which provides a simple synthetic method for N-aryl indoles.展开更多
Selective detection of multiple analytes in a compact design with dual-modality and theranostic features presents great challenges. Herein, we wish to report a coumarin-thiazolidine masked D-penicillamine based dual-m...Selective detection of multiple analytes in a compact design with dual-modality and theranostic features presents great challenges. Herein, we wish to report a coumarin-thiazolidine masked D-penicillamine based dual-modality fluorescent probe COU-DPA-1 for selective detection, differentiation, and detoxification of multiple heavy metal ions(Ag^(+), Hg^(2+), Cu^(2+)). The probe shows divergent fluorescence(FL)/circular dichroism(CD) responses via divergent bond-cleavage cascade reactions(metal ion promoted C-S cleavage and hydrolysis at two distinctive cleavage sites): FL “turn-off” and CD “turn-on” for Ag+(no hydrolysis), FL “turn-on” and CD “turn-off” for Hg^(+)(imine hydrolysis), and FL “self-threshold ratiometric” and CD “turn-off” for excess Cu^(2+)(lactone and imine hydrolysis), providing the first example of a fluorescence/CD dual-modality probe for multiple species with complimentary responses. Moreover, the bond-cleavage cascade reactions also lead to the formation of D-penicillamine heavy metal ion complexes for potential detoxification treatments.展开更多
We report a turn-on fluorescent probe for H2S through a cascade reaction using a new trap group 4- （bromomethyl）benzoate, based on excited-state intramolecular proton transfer （ESIPT） sensing mechanism. The probe ...We report a turn-on fluorescent probe for H2S through a cascade reaction using a new trap group 4- （bromomethyl）benzoate, based on excited-state intramolecular proton transfer （ESIPT） sensing mechanism. The probe showed good selectivity and high sensitivity towards H2S and it was capable of detecting and imaging H2S in living HeLa cells, indicating its potential biological applications.展开更多
An N-heterocyclic carbene(NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-basedβ-hydroxyaldehyde has been developed.The ring opening-closure process enables the diastereodivergent synthesis of spir...An N-heterocyclic carbene(NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-basedβ-hydroxyaldehyde has been developed.The ring opening-closure process enables the diastereodivergent synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters by simply changing the reaction solvents(THF or DCE).The Michael/aldol/retro-aldol/aldol sequential protocol allows the diastereodivergent synthesis of spirocyclopentaneoxindoles from 3-substituted oxindole andα,β-unsaturated aldehyde under the relay catalysis of a chiral secondary amine and an NHC catalyst.Moreover,four stereoisomers of the product can be selectively provided by using different combinations of a chiral secondary amine and a solvent.展开更多
The cascade reactions of alkyl α-diazoesters and ynones using Al(OTf)_(3) as the catalyst are described.A series of 4-substituted pyrazoles were obtained via [3+2] cycloaddition,1,5-ester shift,1,3-H shift,and N-H in...The cascade reactions of alkyl α-diazoesters and ynones using Al(OTf)_(3) as the catalyst are described.A series of 4-substituted pyrazoles were obtained via [3+2] cycloaddition,1,5-ester shift,1,3-H shift,and N-H insertion process.Deuterium labelling experiments,kinetic studies and control experiments were carried out for the rationalization of the mechanism.展开更多
Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridg...Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1,4‑dien-3-ones.Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of t BuOK in commercially available EtOH solvent at 60℃.Notably,the simple reactions can be run on a gram scale.Mechanistically,bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.展开更多
An asymmetric total synthesis of(+)-21-epi-eburnamonine has been achieved.Key features of the synthesis include a visible-light photocatalytic intra-/intramolecular radical cascade reaction to assemble the tetracyclic...An asymmetric total synthesis of(+)-21-epi-eburnamonine has been achieved.Key features of the synthesis include a visible-light photocatalytic intra-/intramolecular radical cascade reaction to assemble the tetracyclic ABCD ring system,and a highly diastereoselective Johnson-Claisen rearrangement to establish the C20 all-carbon quaternary stereocenter.展开更多
A novel and efficient approach for the straightforward synthesis of biologically significant acenaphtho[1,2-b]quinoline derivatives in good yields utilizing CuI as a catalyst with a broad array of substrates has been ...A novel and efficient approach for the straightforward synthesis of biologically significant acenaphtho[1,2-b]quinoline derivatives in good yields utilizing CuI as a catalyst with a broad array of substrates has been developed. The strategy features as a CuI-catalyzed cascade reaction involving the formation of two new C–C bonds and one new C–N bond with high atom economy. A proposed mechanism for the reaction is described.展开更多
An efficient method has been developed for the cascade synthesis of azo[1,2-a]indolones from azoles and2-fluoroaldehydes based on an iron-catalyzed SNAr and a direct acylation reaction.A number of azo[1,2-a]indolones ...An efficient method has been developed for the cascade synthesis of azo[1,2-a]indolones from azoles and2-fluoroaldehydes based on an iron-catalyzed SNAr and a direct acylation reaction.A number of azo[1,2-a]indolones containing different azole rings and substituents were obtained in good yields.展开更多
The integration of natural enzymes and nanomaterials with tailorable enzyme-like activities is highly desirable for cascade reactions.However,the ambiguous structure-performance relationship and uncontrollable activit...The integration of natural enzymes and nanomaterials with tailorable enzyme-like activities is highly desirable for cascade reactions.However,the ambiguous structure-performance relationship and uncontrollable activity are obstacles to their further application.Herein,we modulated the catalase(CAT)-like activity of atomically precise Au_(25)(MPA)_(18)(MPA=3-mercaptopropionic acid)nanoclusters(AuNCs)using single-heteroatom doping.Au_(24)Cu_(1)(MPA)_(18)(Au_(24)Cu_(1))exhibited elevated CAT-like activity.We revealed that the Cu atom is more favorable than Au in the NCs for stabilizing hydroxyl radicals during the catalytic process.Moreover,the synergetic effects of uric acid(UA)oxidation catalyzed by urate oxidase(UOx),oxygen generation from the toxic intermediate hydrogen peroxide facilitated by Au_(24)Cu_(1),and the protective function and nanoconfinement effect of zeolitic imidazolate framework-8(ZIF-8)enabled the UOx-Au_(24)Cu_(1)@ZIF-8 composite to degrade more UA.This study provides essential guidance for creating a tailored and biocompatible cascade system.展开更多
To effectively exploit the tumor microenvironment(TME),TME-responsive nanocarriers based on cascade reactions have received much attention.In this study,we designed a novel nanoparticle PB@SiO_(2)@MnO_(2)@P-Arg(PMP)to...To effectively exploit the tumor microenvironment(TME),TME-responsive nanocarriers based on cascade reactions have received much attention.In this study,we designed a novel nanoparticle PB@SiO_(2)@MnO_(2)@P-Arg(PMP)to construct a cascade reaction nanoplatform.While using biosafety Prussian blue(PB)for photothermal therapy(PTT),this nanoplatform uses silica(SiO_(2))as an intermediate layer to assemble Prussian blue and manganese dioxide(MnO_(2))into a core-shell structure,which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy(CDT)resulting from glutathione(GSH)depletion and Fenton-like reaction.The released Mn2+can also be used for magnetic resonance imaging(MRI).Through the cascade reaction,poly-l-arginine(P-Arg)coated on the surface of the nanoparticles can react with hydroxyl radical(•OH)obtained from the Fenton-like reaction to release nitric oxide(NO),which further reacts with O_(2•)^(−)to produce the more toxic peroxynitrite anion(ONOO−).The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment.In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies,providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions,as well as the application of cascade reactions in multimodal synergistic therapy.展开更多
Presented herein is a novel synthesis of 3-hydroxyfluorenones through the cascade reaction of aryl enaminones with benzyl substituted cyclopropanols.The formation of product is initiated by the introduction of an enon...Presented herein is a novel synthesis of 3-hydroxyfluorenones through the cascade reaction of aryl enaminones with benzyl substituted cyclopropanols.The formation of product is initiated by the introduction of an enone moiety onto aryl enaminone with cyclopropanol as a homoenolate precursor through aryl C−H bond activation,followed by intramolecular enamine Michael addition,enol Michael addition,amine elimination and aromatization-driven oxidative dehydrogenation.To our knowledge,this should be the first example for the specific synthesis of 3-hydroxyfluorenone derivatives via simultaneous formation of both indenone and phenol scaffolds through cascade C−H/C−C/C−N bond activation and three C−C bond formation.In general,this newly developed protocol features easily accessible substrates,synthetically and pharmaceutically valuable products,unique reaction pathway,good compatibility with various functional groups and ready scalability.展开更多
A novel method for the asymmetric synthesis of 1,7-annulated indazoles has been developed via bifunctional Brønsted base catalyzed cascade reaction.This process enabled the formation of multiple chiral centers in...A novel method for the asymmetric synthesis of 1,7-annulated indazoles has been developed via bifunctional Brønsted base catalyzed cascade reaction.This process enabled the formation of multiple chiral centers including a quaternary carbon center in high yields with excellent diastereoselectivities and enantioselectivities.The reaction exhibited broad functional group tolerance and mild reaction conditions.展开更多
In on-surface synthesis,dimers are typically utilized to explore reaction mechanisms or as intermediates in the formation of final products.However,constructing the innovative nanostructures with dimers as building bl...In on-surface synthesis,dimers are typically utilized to explore reaction mechanisms or as intermediates in the formation of final products.However,constructing the innovative nanostructures with dimers as building blocks remains challenging.Here,using non-planar 2,2′,7,7′-tetrabromo-9,9′-biflurenyliden molecules,we have successfully synthesized dimeric covalent organic frameworks(COFs)on the Au(111)surface through a temperature-controlled cascade reaction.Notably,the H-H steric hindrance within precursors caused by double bonds leads to selective stepwise debromination during the thermal annealing,which promotes the dimerization through intermolecular Ullmann coupling and cyclodehydrogenation reaction to form COFs primarily constituted by dimer building blocks.Combining scanning tunneling microscopy/spectroscopy and density functional theory calculations,we have precisely confirmed the structural evolution and reaction mechanism.Furthermore,by introducing Ag adatoms to form C−Ag−C intermediates,we have successfully regulated the reaction path and synthesized one-dimensional nanoribbons with dimers as building blocks.This work not only validates the strategy of synthesizing dimeric nanostructures on different surfaces through cascade reactions induced by precursor design,but also enriches the research field of surface synthesis of COFs and nanoribbons.展开更多
Nickel-catalyzed reductive cross-coupling(RCC)reactions between alkenes and alkyl electrophiles are undoubtedly the attractive approaches to new functionalized heterocycles.However,the alkylation reagents are still ra...Nickel-catalyzed reductive cross-coupling(RCC)reactions between alkenes and alkyl electrophiles are undoubtedly the attractive approaches to new functionalized heterocycles.However,the alkylation reagents are still rather limited for the arylalkylation of tethered alkenes via RCC reactions.Thus,developing more robust methods to access heterocycles from stable and readily available starting materials under RCC conditions is still highly challenging and desirable.A new nickelcatalyzed reductive arylalkylation of tethered alkenes with cyclosulfonium salts as C(sp^(3))electrophiles to access the sulfurcontaining oxindoles is developed.This tandem ring-opening/cyclization/reductive coupling protocol enables the efficient construction of various oxindoles bearing all-carbon quaternary centers under mild conditions with broad functional group tolerance.Notably,many drug derivatives are readily functionalized using the developed protocol.展开更多
Utilizing the unique tumor microenvironment(TME)to conduct chemical reactions for cancer treatment becomes a hot topic recently.Nevertheless,single chemical reaction in TME is often restricted by scanty reaction subst...Utilizing the unique tumor microenvironment(TME)to conduct chemical reactions for cancer treatment becomes a hot topic recently.Nevertheless,single chemical reaction in TME is often restricted by scanty reaction substrates and slow reaction rate.Meanwhile,the toxic substances produced by the reactions are usually not enough to kill cancer cells.Herein,using covalent organic frameworks(COFs)as the template,Au nanoparticles(Au NPs)were subsequently grown on the surface of the COF,then a thin layer of manganese dioxide(MnO2)was coated over the material,and finally hyaluronic acid(HA)was introduced to improve the biocompatibility.The resultant product,named COF-Au-MnO2,was involved in several processes to form cascade reactions in the TME.Specifically,under hypoxic conditions,COF-Au-MnO2 could react with intratumoral H2O2 to produce O2 to enhance the type II photodynamic therapy(PDT),and Au NPs could decompose glucose to promote starving-like therapy.Besides,starving-like therapy can also produce H2O2 to increase O2 production.Simultaneously,MnO2 can consume glutathione(GSH)to enhance the antitumor efficacy,and the released Mn2+could be used for T1-weighted magnetic resonance imaging(MRI).Both in vitro and in vivo experiments had proven excellent cancer cell killing effect and antitumor efficacy of COF-Au-MnO2via such a cycle-like process.展开更多
Emerging nanozymes with natural enzyme-mimicking catalytic activities have inspired extensive research interests due to their high stability,low cost,and simple preparation,especially in the field of catalytic tumor t...Emerging nanozymes with natural enzyme-mimicking catalytic activities have inspired extensive research interests due to their high stability,low cost,and simple preparation,especially in the field of catalytic tumor therapy.Here,bio-breakable nanozymes based on glucose-oxidase(GOx)-loaded biomimetic Au–Ag hollow nanotriangles(Au–Ag–GOx HTNs)are designed,and they trigger an near-infrared(NIR)-II-driven plasmon-enhanced cascade catalytic reaction through regulating tumor microenvironment(TME)for highly efficient tumor therapy.Firstly,GOx can effectively trigger the generation of gluconic acid(H+)and hydrogen peroxide(H2O2),thus depleting nutrients in the tumor cells as well as modifying TME to provide conditions for subsequent peroxidase(POD)-like activity.Secondly,NIR-II induced surface plasmon resonance can induce hot electrons to enhance the catalytic activity of Au–Ag–GOx HTNs,eventually boosting the generation of hydroxyl radicals(•OH).Interestingly,the generated H2O2 and H+can simultaneously induce the degradation of Ag nanoprisms to break the intact triangle nanostructure,thus promoting the excretion of Au–Ag–GOx HTNs to avoid the potential risks of drug metabolism.Overall,the NIR-II driven plasmon-enhanced catalytic mechanism of this bio-breakable nanozyme provides a promising approach for the development of nanozymes in tumor therapy.展开更多
文摘A novel synthesis of C2-spiroindoline derivatives based on the cascade reaction of 2-aryl-3H-indoles with cyclo- propanols is presented. The formation of product involves Rh(III)-catalyzed aryl C(sp2)—H bond alkylation of 2-aryl- 3H-indole, which is followed by intramolecular spiroannulation. In this tandem process, cyclopropanol acts as not only an alkylating agent but also a masked nucleophile to take part in the construction of the spirocyclic scaffold. Meanwhile, air acts as an economical and sustainable oxidant to promote the regeneration of the active catalyst. By using this method, hybrid compounds containing the central scaffolds of some clinical drugs were prepared effectively. In general, this newly developed method has advantages such as easily obtainable substrates, concise synthetic procedure, excellent atom-economy, good compatibility with diverse functional groups and ready scalability.
基金supported by the National Natural Science Foundation of China Project(No.22208321)the China Postdoctoral Science Foundation Project(No.2022M720130)+1 种基金the Key Scientific Research Project of Henan Province High Education Institutions(No.24A350018)the Natural Science Foundation of Henan Province-Outstanding Youth Foundation(No.232300421058)。
文摘Wound healing in diabetic patients presents significant challenges due to heightened risks of bacterial infection,elevated glucose levels,and insufficient angiogenesis.Nanozymes are widely employed for wound healing,but most current nanozyme systems exhibit only moderate activity limited by incompatible reaction microenvironments including p H and hydrogen peroxide(H_(2)O_(2))concentration.Herein,a glucoseactivated nanozyme hydrogel was developed using bovine serum albumin(BSA)-modified gold nanoparticles(Au NPs)attached to a two-dimensional(2D)metal-organic framework(MOF)(Cu-TCPP(Fe)@Au@BSA)by an in situ growth method.The Au NPs function as a glucose oxidase(GOx)-like enzyme,converting glucose to gluconic acid and H_(2)O_(2),triggering the peroxidase(POD)-like activity of Cu-TCPP(Fe)to produce hydroxyl radicals(·OH),effectively eliminating bacteria.Additionally,the modification of BSA reduces the Au NP size,enhancing enzyme activity.Both in vitro and in vivo tests demonstrate that this nanozyme hydrogel can be activated by the microenvironment to lower blood glucose,eliminate bacterial infections,and promote epithelial formation and collagen deposition,thus accelerating diabetic wound healing effectively.The multifunctional nanozyme hydrogel dressing developed in this study presents a promising therapeutic approach to enhance diabetic wound healing.
基金Project supported by the Natural Science Foundation of Jiangsu Province (BK20210066)Natural Science Foundation of Heilongjiang Province (ZD2022E007).
文摘A composite metal-organic frameworks(MOFs)structure,designated as Co-hmta@La-salen,was synthesized through coordination interactions between a one-dimensional lanthanum MOFs(La-salen)with high density of uncoordinated imine(-CH=N-)groups and a cobalt-based MOFs(Co-hmta)structure prepared using hydrogen bonding stacking with hexamethylenetetramine(hmta)as the organic ligand.Subsequently,the Co-hmta@La-salen composite was chosen as a template for the pyrolysis process to synthesize a La(OH)_(3)supported metallic Co catalyst incorporating carbon-nitrogen(Co/La(OH)_(3)-CNhmta)catalyst.The catalytic results show that Co/La(OH)_(3)-CN-hmta(54%and 46%selectivity for aniline and N-phenylbenzylamine,respectively)displays superior cascade performance compared to classic Co/La(OH)_(3)-CN-nit catalyst(69%and 31%selectivity for aniline and N-phenylbenzylamine,respectively).Moreover,the kinetic test results indicate that N-alkylation is the rate-limiting step of the overall cascade reaction.The Co/La(OH)_(3)-CN-hmta catalyst can be separated from the reaction system using a magnet,and it also exhibits good cyclic stability.All of these suggest that the“MOFs plus MOFs via coordination”templating method can be employed as an efficient strategy for the preparation of supported catalysts.
基金supported by the Intercollegiate Key Scientific Research Projects of Henan Province(15A150018)~~
文摘An efficient Cu catalyzed selective arylation/annulation cascade reaction of 2-alkynylanilines with diaryliodonium salts was developed.This reaction was selective to N-arylation instead of C-arylation,which provides a simple synthetic method for N-aryl indoles.
基金supported by the National Natural Science Foundation of China (Nos. 21577037 and 21738002)the State Key Laboratory of Bioreactor Engineering, Shanghai Natural Science Fund (No. 20ZR1414700)+2 种基金Shanghai Sailing Program (No. 19YF1412500)Natural Science Basic Research Program of Shaanxi (No. 2019JQ-924)Key Breeding Program by Collaborative Innovation Center of Green Manufacturing Technology for Traditional Chinese Medicine in Shaanxi Province (No. 2019XT-1-03)。
文摘Selective detection of multiple analytes in a compact design with dual-modality and theranostic features presents great challenges. Herein, we wish to report a coumarin-thiazolidine masked D-penicillamine based dual-modality fluorescent probe COU-DPA-1 for selective detection, differentiation, and detoxification of multiple heavy metal ions(Ag^(+), Hg^(2+), Cu^(2+)). The probe shows divergent fluorescence(FL)/circular dichroism(CD) responses via divergent bond-cleavage cascade reactions(metal ion promoted C-S cleavage and hydrolysis at two distinctive cleavage sites): FL “turn-off” and CD “turn-on” for Ag+(no hydrolysis), FL “turn-on” and CD “turn-off” for Hg^(+)(imine hydrolysis), and FL “self-threshold ratiometric” and CD “turn-off” for excess Cu^(2+)(lactone and imine hydrolysis), providing the first example of a fluorescence/CD dual-modality probe for multiple species with complimentary responses. Moreover, the bond-cleavage cascade reactions also lead to the formation of D-penicillamine heavy metal ion complexes for potential detoxification treatments.
基金financially supported by the 973 Program (No.2013CB933800)National Natural Science Foundation of China (Nos.21525206,21402216,21272243)the Fundamental Research Funds for the Central Universities and Beijing Municipal Commission of Education
文摘We report a turn-on fluorescent probe for H2S through a cascade reaction using a new trap group 4- （bromomethyl）benzoate, based on excited-state intramolecular proton transfer （ESIPT） sensing mechanism. The probe showed good selectivity and high sensitivity towards H2S and it was capable of detecting and imaging H2S in living HeLa cells, indicating its potential biological applications.
基金financial support from Ministry of Science and Technology of China (No.2019ZX09721001-008)National Natural Science Foundation of China (Nos.81773890,22001024,82073997)the “Thousand Talents Program” of Sichuan Province and Xinglin Scholar Research Premotion Project of CDUTCM。
文摘An N-heterocyclic carbene(NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-basedβ-hydroxyaldehyde has been developed.The ring opening-closure process enables the diastereodivergent synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters by simply changing the reaction solvents(THF or DCE).The Michael/aldol/retro-aldol/aldol sequential protocol allows the diastereodivergent synthesis of spirocyclopentaneoxindoles from 3-substituted oxindole andα,β-unsaturated aldehyde under the relay catalysis of a chiral secondary amine and an NHC catalyst.Moreover,four stereoisomers of the product can be selectively provided by using different combinations of a chiral secondary amine and a solvent.
基金supported by the National Natural Science Foundation of China(Nos.21625205 and U19A2014)。
文摘The cascade reactions of alkyl α-diazoesters and ynones using Al(OTf)_(3) as the catalyst are described.A series of 4-substituted pyrazoles were obtained via [3+2] cycloaddition,1,5-ester shift,1,3-H shift,and N-H insertion process.Deuterium labelling experiments,kinetic studies and control experiments were carried out for the rationalization of the mechanism.
基金National Natural Science Foundation of China(NSFC,Nos.21772032,21877206,and 22101074)the 111 Project(No.D17007)+3 种基金Excellent Youth Foundation of Henan Scientific Committee(No.222300420012)China Postdoctoral Science Foundation(No.2019M660173)the Natural Science Foundation of Henan Province(No.202300410233)Henan Key Laboratory of Organic Functional Molecules and Drug Innovation for financial support。
文摘Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1,4‑dien-3-ones.Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of t BuOK in commercially available EtOH solvent at 60℃.Notably,the simple reactions can be run on a gram scale.Mechanistically,bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.
基金surpport from National Natural Science Foundation of China(21921002 and 21991114)National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(2018ZX09711003-015 and 2018ZX09711001-005-004).
文摘An asymmetric total synthesis of(+)-21-epi-eburnamonine has been achieved.Key features of the synthesis include a visible-light photocatalytic intra-/intramolecular radical cascade reaction to assemble the tetracyclic ABCD ring system,and a highly diastereoselective Johnson-Claisen rearrangement to establish the C20 all-carbon quaternary stereocenter.
基金the National Key Technology R&D Program‘‘New Drug Innovation’’of China(No.2013ZX09402103)
文摘A novel and efficient approach for the straightforward synthesis of biologically significant acenaphtho[1,2-b]quinoline derivatives in good yields utilizing CuI as a catalyst with a broad array of substrates has been developed. The strategy features as a CuI-catalyzed cascade reaction involving the formation of two new C–C bonds and one new C–N bond with high atom economy. A proposed mechanism for the reaction is described.
基金financially supported by the Natural Science Foundation of China(Nos.21302135 and 21272169)Taizhou Science & Technology program(No.111ZD02)
文摘An efficient method has been developed for the cascade synthesis of azo[1,2-a]indolones from azoles and2-fluoroaldehydes based on an iron-catalyzed SNAr and a direct acylation reaction.A number of azo[1,2-a]indolones containing different azole rings and substituents were obtained in good yields.
基金financially supported by the National Natural Science Foundation of China(No.92061201,21825106,22001238,and 22001235)the National Key R&D Program of China(2021YFA1200301)+3 种基金the China Postdoctoral Science Foundation(2019M662516)the Zhongyuan Thousand Talents(Zhongyuan Scholars)Program of Henan Province(234000510007)the 2023 Graduate Education Research Project of Zhengzhou University(YJSJY202317)supported by the Tianjian Laboratory of Advanced Biomedical Sciences.
文摘The integration of natural enzymes and nanomaterials with tailorable enzyme-like activities is highly desirable for cascade reactions.However,the ambiguous structure-performance relationship and uncontrollable activity are obstacles to their further application.Herein,we modulated the catalase(CAT)-like activity of atomically precise Au_(25)(MPA)_(18)(MPA=3-mercaptopropionic acid)nanoclusters(AuNCs)using single-heteroatom doping.Au_(24)Cu_(1)(MPA)_(18)(Au_(24)Cu_(1))exhibited elevated CAT-like activity.We revealed that the Cu atom is more favorable than Au in the NCs for stabilizing hydroxyl radicals during the catalytic process.Moreover,the synergetic effects of uric acid(UA)oxidation catalyzed by urate oxidase(UOx),oxygen generation from the toxic intermediate hydrogen peroxide facilitated by Au_(24)Cu_(1),and the protective function and nanoconfinement effect of zeolitic imidazolate framework-8(ZIF-8)enabled the UOx-Au_(24)Cu_(1)@ZIF-8 composite to degrade more UA.This study provides essential guidance for creating a tailored and biocompatible cascade system.
基金supported by the National Natural Science Foundation of China(Grant Nos.:51973053 and 51773055).
文摘To effectively exploit the tumor microenvironment(TME),TME-responsive nanocarriers based on cascade reactions have received much attention.In this study,we designed a novel nanoparticle PB@SiO_(2)@MnO_(2)@P-Arg(PMP)to construct a cascade reaction nanoplatform.While using biosafety Prussian blue(PB)for photothermal therapy(PTT),this nanoplatform uses silica(SiO_(2))as an intermediate layer to assemble Prussian blue and manganese dioxide(MnO_(2))into a core-shell structure,which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy(CDT)resulting from glutathione(GSH)depletion and Fenton-like reaction.The released Mn2+can also be used for magnetic resonance imaging(MRI).Through the cascade reaction,poly-l-arginine(P-Arg)coated on the surface of the nanoparticles can react with hydroxyl radical(•OH)obtained from the Fenton-like reaction to release nitric oxide(NO),which further reacts with O_(2•)^(−)to produce the more toxic peroxynitrite anion(ONOO−).The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment.In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies,providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions,as well as the application of cascade reactions in multimodal synergistic therapy.
基金We are grateful to Postdoctoral Research Grant in Henan Province(HN2022041)Key Research Projects of Universities in Henan Province(24A150018)NMPA Key Laboratory for Research and Evaluation of Innovative Drug,Henan Key Laboratory of Organic Functional Molecules and Drug Innovation,and 111 Project(D17007)for financial support.
文摘Presented herein is a novel synthesis of 3-hydroxyfluorenones through the cascade reaction of aryl enaminones with benzyl substituted cyclopropanols.The formation of product is initiated by the introduction of an enone moiety onto aryl enaminone with cyclopropanol as a homoenolate precursor through aryl C−H bond activation,followed by intramolecular enamine Michael addition,enol Michael addition,amine elimination and aromatization-driven oxidative dehydrogenation.To our knowledge,this should be the first example for the specific synthesis of 3-hydroxyfluorenone derivatives via simultaneous formation of both indenone and phenol scaffolds through cascade C−H/C−C/C−N bond activation and three C−C bond formation.In general,this newly developed protocol features easily accessible substrates,synthetically and pharmaceutically valuable products,unique reaction pathway,good compatibility with various functional groups and ready scalability.
基金the Qingdao Marine Science and Technology Center(No.2022QNLM030003-2)the Fundamental Research Funds for the Central Universities,Taishan Scholar Program of Shandong Province(No.tsqn201909056)+1 种基金Natural Science Foundation of Shandong Province(No.ZR2024MB122)National Natural Science Foundation of China(No.22171251)for financial support.
文摘A novel method for the asymmetric synthesis of 1,7-annulated indazoles has been developed via bifunctional Brønsted base catalyzed cascade reaction.This process enabled the formation of multiple chiral centers including a quaternary carbon center in high yields with excellent diastereoselectivities and enantioselectivities.The reaction exhibited broad functional group tolerance and mild reaction conditions.
基金supported by the National Natural Science Foundation of China(Nos.62271238,22372074,62301240)Yunnan Fundamental Research Projects(Nos.202201AT070078,202201BE070001-009 and 202301AW070017)+3 种基金the Major Basic Research Project of Science and Technology of Yunnan(202302AG050007)Yunnan Innovation Team of Graphene Mechanism Research and Application Industrialization(202305AS350017)Graphene Application and Engineering Research Center of Education Department of Yunnan Providence(KKPP202351001)Numerical computations were performed at Hefei Advanced Computing Center.
文摘In on-surface synthesis,dimers are typically utilized to explore reaction mechanisms or as intermediates in the formation of final products.However,constructing the innovative nanostructures with dimers as building blocks remains challenging.Here,using non-planar 2,2′,7,7′-tetrabromo-9,9′-biflurenyliden molecules,we have successfully synthesized dimeric covalent organic frameworks(COFs)on the Au(111)surface through a temperature-controlled cascade reaction.Notably,the H-H steric hindrance within precursors caused by double bonds leads to selective stepwise debromination during the thermal annealing,which promotes the dimerization through intermolecular Ullmann coupling and cyclodehydrogenation reaction to form COFs primarily constituted by dimer building blocks.Combining scanning tunneling microscopy/spectroscopy and density functional theory calculations,we have precisely confirmed the structural evolution and reaction mechanism.Furthermore,by introducing Ag adatoms to form C−Ag−C intermediates,we have successfully regulated the reaction path and synthesized one-dimensional nanoribbons with dimers as building blocks.This work not only validates the strategy of synthesizing dimeric nanostructures on different surfaces through cascade reactions induced by precursor design,but also enriches the research field of surface synthesis of COFs and nanoribbons.
基金Project supported by the National Natural Science Foundation of China(No.22271170)the Taishan Scholars Program from Shandong Province(No.tsqn202408197)the Natural Science Foundation of Shandong Province(No.ZR2024QB154)。
文摘Nickel-catalyzed reductive cross-coupling(RCC)reactions between alkenes and alkyl electrophiles are undoubtedly the attractive approaches to new functionalized heterocycles.However,the alkylation reagents are still rather limited for the arylalkylation of tethered alkenes via RCC reactions.Thus,developing more robust methods to access heterocycles from stable and readily available starting materials under RCC conditions is still highly challenging and desirable.A new nickelcatalyzed reductive arylalkylation of tethered alkenes with cyclosulfonium salts as C(sp^(3))electrophiles to access the sulfurcontaining oxindoles is developed.This tandem ring-opening/cyclization/reductive coupling protocol enables the efficient construction of various oxindoles bearing all-carbon quaternary centers under mild conditions with broad functional group tolerance.Notably,many drug derivatives are readily functionalized using the developed protocol.
基金the National Natural Science Foundation of China(21471145)the Science and Technology Development Planning Project of Jilin Province(20170101179JC)the“Hundred Talents Program”of Chinese Academy of Sciences。
文摘Utilizing the unique tumor microenvironment(TME)to conduct chemical reactions for cancer treatment becomes a hot topic recently.Nevertheless,single chemical reaction in TME is often restricted by scanty reaction substrates and slow reaction rate.Meanwhile,the toxic substances produced by the reactions are usually not enough to kill cancer cells.Herein,using covalent organic frameworks(COFs)as the template,Au nanoparticles(Au NPs)were subsequently grown on the surface of the COF,then a thin layer of manganese dioxide(MnO2)was coated over the material,and finally hyaluronic acid(HA)was introduced to improve the biocompatibility.The resultant product,named COF-Au-MnO2,was involved in several processes to form cascade reactions in the TME.Specifically,under hypoxic conditions,COF-Au-MnO2 could react with intratumoral H2O2 to produce O2 to enhance the type II photodynamic therapy(PDT),and Au NPs could decompose glucose to promote starving-like therapy.Besides,starving-like therapy can also produce H2O2 to increase O2 production.Simultaneously,MnO2 can consume glutathione(GSH)to enhance the antitumor efficacy,and the released Mn2+could be used for T1-weighted magnetic resonance imaging(MRI).Both in vitro and in vivo experiments had proven excellent cancer cell killing effect and antitumor efficacy of COF-Au-MnO2via such a cycle-like process.
基金This work was supported by the Young Elite Scientists Sponsorship Program by Tianjin(No.0701320001)major special project of Tianjin(No.0402080005).
文摘Emerging nanozymes with natural enzyme-mimicking catalytic activities have inspired extensive research interests due to their high stability,low cost,and simple preparation,especially in the field of catalytic tumor therapy.Here,bio-breakable nanozymes based on glucose-oxidase(GOx)-loaded biomimetic Au–Ag hollow nanotriangles(Au–Ag–GOx HTNs)are designed,and they trigger an near-infrared(NIR)-II-driven plasmon-enhanced cascade catalytic reaction through regulating tumor microenvironment(TME)for highly efficient tumor therapy.Firstly,GOx can effectively trigger the generation of gluconic acid(H+)and hydrogen peroxide(H2O2),thus depleting nutrients in the tumor cells as well as modifying TME to provide conditions for subsequent peroxidase(POD)-like activity.Secondly,NIR-II induced surface plasmon resonance can induce hot electrons to enhance the catalytic activity of Au–Ag–GOx HTNs,eventually boosting the generation of hydroxyl radicals(•OH).Interestingly,the generated H2O2 and H+can simultaneously induce the degradation of Ag nanoprisms to break the intact triangle nanostructure,thus promoting the excretion of Au–Ag–GOx HTNs to avoid the potential risks of drug metabolism.Overall,the NIR-II driven plasmon-enhanced catalytic mechanism of this bio-breakable nanozyme provides a promising approach for the development of nanozymes in tumor therapy.
