A visible-light-induced spirocyclizative hydroarylation via reductive dearomatization of a series of non activated arenes including 2-phenyl indoles and naphthalene derivatives under mild conditions is de scribed.An i...A visible-light-induced spirocyclizative hydroarylation via reductive dearomatization of a series of non activated arenes including 2-phenyl indoles and naphthalene derivatives under mild conditions is de scribed.An intriguing chemoselective dearomative hydroarylation of 2-phenyl indoles is presented.Th dearomative hydroarylation protocol rapidly delivers valuable spirocycles with carbon-carbon doub bonds from readily accessible aromatic precursors in a single step.展开更多
A new method for the synthesis of 3-thioazaspiro[4,5]trienones was developed using Pd nanoparticle catalysts,which are highly efficient,environmentally friendly and recyclable.Alkynes and thiophene phenols are effecti...A new method for the synthesis of 3-thioazaspiro[4,5]trienones was developed using Pd nanoparticle catalysts,which are highly efficient,environmentally friendly and recyclable.Alkynes and thiophene phenols are effectively cyclized by Pd/ZrO2 catalyst under visible light irradiation.The present protocol simply utilizes visible light as the safe and ecofriendly energy source,and the Pd/ZrO2 nanocomposite as photocatalyst provides a simple and practical approach to various 3-thioazaspiro[4,5]trienones in moderate conditions to high yields.展开更多
The development of efficient and sustainable methods to obtain spirocyclic compounds is of significance as these structures are widely found in pharmaceuticals and agrochemicals.Herein,we disclose an electrochemical d...The development of efficient and sustainable methods to obtain spirocyclic compounds is of significance as these structures are widely found in pharmaceuticals and agrochemicals.Herein,we disclose an electrochemical dearomative spirocyclization of N-acyl sulfonamides in a continuous-flow cell.The reaction is simple and efficient without external catalysts or supporting electrolytes and could be applied in a decagram-scale synthesis.展开更多
Herein,we report a condition-controlled divergent synthesis of spiro indene-2,1'-isoindolinones and spiro isochroman-3,1'-isoindolinones through cobalt-catalyzed formal[4+1]and[4+1+1]spirocyclization of aromat...Herein,we report a condition-controlled divergent synthesis of spiro indene-2,1'-isoindolinones and spiro isochroman-3,1'-isoindolinones through cobalt-catalyzed formal[4+1]and[4+1+1]spirocyclization of aromatic amides with 2-diazo-1H-indene-1,3(2H)-dione.When the reaction is carried out under air in ethyl acetate,spiro indene-2,1'-isoindolinones are formed through Co(II)-catalyzed C—H/N—H[4+1]spirocyclization.When the reaction is run under O2 in CH3CN,on the other hand,spiro isochroman-3,1'-isoindolinones are generated through Baeyer-Villiger oxidation of the in situ formed spiro indene-2,1'-isoindolinones with O2 as a cheaper and environmental-friendly oxygen source.In general,these protocols have advantages such as using non-precious and earth-abundant metal catalyst,no extra additive,high efficiency and regioselectivity.A gram-scale synthesis and the removal of the directing group further highlight its utility.展开更多
Transition-metal-catalyzed cross-coupling reactions as very efficient and atom-economical approaches have been widely used to build up complex heterocyclic compounds.However,modification of 2-oxyl benzimidazole skelet...Transition-metal-catalyzed cross-coupling reactions as very efficient and atom-economical approaches have been widely used to build up complex heterocyclic compounds.However,modification of 2-oxyl benzimidazole skeleton using maleimide compounds via C–H activation has remained unprecedented.Herein,we developed a rhodium(III)-catalyzed[5+1]cascade spiroannulation to construct diversified novel benzimidazole-incorporated spirosuccinimide derivatives from 2-oxyl benzimidazoles and maleimides.展开更多
A new synthesis of spirocyclic oxindole analogue spiro[piperidine-4,3＇-pyrrolol2,3-b]pyridin]-2＇（1＇H）-one 1 is described. The key steps involve dialkylation of arylacetonitrile and cyclization of the azaoxindole ...A new synthesis of spirocyclic oxindole analogue spiro[piperidine-4,3＇-pyrrolol2,3-b]pyridin]-2＇（1＇H）-one 1 is described. The key steps involve dialkylation of arylacetonitrile and cyclization of the azaoxindole ring by an intramolecular Buchwald-Hartwig amidation of carboxylic amide and aryl chloride. A small library was obtained by reductive amination of 1 with various aldehydes and was screened against human lung cancer cell A549, human liver cancer cell BEL7402, and human colon cancer cell HCT-8. The results show that most of the library compounds 2 have some inhibitory activities. 2-（Trifluoromethoxy） benzylic substituted spirocyclic azaoxindole 2e was identified as a nanomolar inhibitor against human lung cancer cell A-549 （IC50 = 50 nmol/L）.展开更多
One new spirocyclic alkaloid,5-isopentenyl-cryptoechinuline D(1),along with 11 known compounds(2–12),were iso-lated from a marine fungus Aspergillus ruber TX-M4-1.The structures of compounds 1–12 were elucidated by ...One new spirocyclic alkaloid,5-isopentenyl-cryptoechinuline D(1),along with 11 known compounds(2–12),were iso-lated from a marine fungus Aspergillus ruber TX-M4-1.The structures of compounds 1–12 were elucidated by spectroscopic evi-dences.Compound 1 was initially isolated as an enantiomer,and further separation of 1 by chiral HPLC afforded a pair of enantio-mers,including(-)-5-isopentenyl-cryptoechinuline D(1a)and(+)-5-isopentenyl-cryptoechinuline D(1b).Their absolute configura-tions were elucidated by ECD spectroscopic data.Compounds 1a,5 and 10 could inhibit thioredoxin reductase(TrxR)activity with IC50 values of 6.2,36.3 and 18.6μmol L^(-1),respectively.Surface plasmon resonance(SPR)study also demonsrated the interactions between compounds 6,8 and Niemann-Pick C1 Like 1(NPC1L1)respectively,which indicate that compounds 6 and 8 are potential NPC1L1 inhibitors.展开更多
A novel spiro-compound（C20 H15 N2 O3 P） has been synthesized and characterized by means of IR and 1H NMR. Its crystal structure was determined by X-ray diffractometry. The crystal belongs to the monoclinic system, s...A novel spiro-compound（C20 H15 N2 O3 P） has been synthesized and characterized by means of IR and 1H NMR. Its crystal structure was determined by X-ray diffractometry. The crystal belongs to the monoclinic system, space group P21 /c with a = 9.1628（7）, b = 12.9490（7）, c = 15.7898（11）, β = 103.952（8）o, Mr = 36.08, V = 1818.2（2）3, Z = 4, Dc = 1.382 g/cm3, F（000） = 788, μ = 0.179 mm-1, R = 0.0701 and wR = 0.1513. The preliminary biological test showed that the title compound has activities against Escherichia coli, S.albus, Bacillus subtilis, Staphylocc- ocusaureus and Micrococcus tetragenus with MIC to be 0.038, 0.038, 0.075, 2.48, and 0.15 mg/mL, respectively.展开更多
The double [3 + 2] cycloaddition of allenoates with nitrile oxides is presented. The reaction worked well under mild reaction conditions to give the spirobidihydroisoxazole in moderate to excellent yields with excelle...The double [3 + 2] cycloaddition of allenoates with nitrile oxides is presented. The reaction worked well under mild reaction conditions to give the spirobidihydroisoxazole in moderate to excellent yields with excellent diastereoselectivities. The two dihydroisoxazole rings have been formed via a sequential double [3 + 2] cycloaddition.展开更多
The present study aimed at identifying cell cycle inhibitors from the fermentation broth of Streptomyces pseudoverticillus YN17707. Activity-guided isolation was performed on ts FT210 cells. Compounds were isolated th...The present study aimed at identifying cell cycle inhibitors from the fermentation broth of Streptomyces pseudoverticillus YN17707. Activity-guided isolation was performed on ts FT210 cells. Compounds were isolated through various chromatographic methods and elucidated by spectroscopic analyses. Flow cytometry was used to evaluate the cell cycle inhibitory activities of the fractions and compounds. Two compounds were obtained and identified as pteridic acid hydrate(1) and pteridic acid C(2), which arrested the ts FT210 cells at the G0/G1 phase with the MIC values being 32.8 and 68.9 μmol·L-1, respectively. These results provide a basis for future development of Compounds 1 and 2 as novel cell cycle inhibitors for cancer therapy.展开更多
Spirohypatone A(1),a spirocyclic PPAP(polycyclic polyprenylated acylphloroglucinol) bearing an unprecedented hexahydro-1’H-spiro[cyclohexane-1,2’-pentalene]-2,4,6-trione core and a new homologue(spirohypatone B,2) w...Spirohypatone A(1),a spirocyclic PPAP(polycyclic polyprenylated acylphloroglucinol) bearing an unprecedented hexahydro-1’H-spiro[cyclohexane-1,2’-pentalene]-2,4,6-trione core and a new homologue(spirohypatone B,2) were isolated from Hypericum patulum together with two known biosynthetic precursors.Compound 1 represents the first spirocyclic PPAP possessing a 5/5/6 carbon ring system,biogenetically derived from the intermediate 3(attack from C-3 to C-12),which was differed from normal spirocyclic PPAPs(attack from C-3 to C-11).In addition,through extensive spectroscopic analysis,an interconversion mechanism of keto-enol of 1 was postulated and confirmed by its methylated reaction.The structures and absolute configurations of 1 and 2 were determined by comprehensive spectroscopic and chemical derivatized methods and X-ray crystallography.Compounds 1,2,and 4 were tested to exhibit cytotoxic activities against several cancer cell lines.展开更多
A simultaneous C2-H arylation and C8-H alkylation of naphthalene ring has been achieved by palladiumcatalyzed cascade reaction of N-(2-halophenyl)-2-(naphthalen-1-yl)acrylamides with aryl iodides,which provides an eff...A simultaneous C2-H arylation and C8-H alkylation of naphthalene ring has been achieved by palladiumcatalyzed cascade reaction of N-(2-halophenyl)-2-(naphthalen-1-yl)acrylamides with aryl iodides,which provides an efficient method for synthesizing various aryl-substituted spirocyclic oxindoles.The protocol enables three C-C bonds formation via an intramolecular Heck reaction and sequentially regioselective C-H bond activation.展开更多
Aminosilane bearing bulky substituents on nitrogen： LH2 （L = Me2Si（NDipp＇）2, Dipp = 2,6-diisopropylphenyl） was reacted with BuLi in toluene. The resulting bulky chelating dianion Me2Si（NDipp）2 was used to synt...Aminosilane bearing bulky substituents on nitrogen： LH2 （L = Me2Si（NDipp＇）2, Dipp = 2,6-diisopropylphenyl） was reacted with BuLi in toluene. The resulting bulky chelating dianion Me2Si（NDipp）2 was used to synthesize the unusual spirocyclic heterotriatomic complex [MeESi（NDipp）2]ESn （1） by its reaction with SnCl4 and the bulky heterotriatomic complex Me2Si（NDipp）2SnPh2 （2） with Ph2SnC12. 1 belongs to the monoclinic system, space group P21/n with a = 13.193（2）, b = 20.663（3）, c = 20.403（3）A, β = 99.954（2）°, V = 5478.3（15） A3, C55H85.5N4Si2Sn, Mr = 977.64, Z = 4, Dc. = 1.185 Mg/m3, μ（MoKa） = 0.547 mm-1, F（000） = 2086, S = 1.000, the final R = 0.0614 and wR = 0.1322 for 14446 observed reflections （1 〉 2σ（I）） and R = 0.0797 and wR = 0.1456 for all data. 2 belongs to the triclinic system, space group P1 with a = 10.36（15）, b = 13.204（7）, c = 14.363（7） A, a = 90.214（10）, β = 106.182（7）, y = 109.854（8）°, V = 1764.4（15） A3, C38HsoN2SiSn, M,. = 681.58, Z = 2, Dc = 1.283 Mg/m^3,μ（MoKa） = 0.785 mm-1, F（000） = 712, S = 1.002, the final R = 0.0498 and wR = 0.0955 for 7533 observed reβections （I 〉 2σ（I）） and R = 0.0676 and wR = 0.1018 for all data. In the structure of 1, the tin atom is located in the spirocyclic center of the two fused four-membered SnN2Si rings. The two complexes were characterized by ^1H NMR, elemental analysis, and single-crystal X-ray structural analysis.展开更多
A simple and direct method for preparation of N-substituted spirocyclic dieSter of □-amino phosphonic acid (4) in high yield is introduced. The reaction consists of the threecomponent reachon of phenylurea (1), an ar...A simple and direct method for preparation of N-substituted spirocyclic dieSter of □-amino phosphonic acid (4) in high yield is introduced. The reaction consists of the threecomponent reachon of phenylurea (1), an aromatic aldehyde (2), and 3,9-dichloro-2,4,8,10-tetraoxa- 3, 9 -diphosphaspiro [5,5] undecane (3) in anhydrous benzene.展开更多
A green and highly efficient strategy for the preparation of bridged spirocyclic compounds via visible-light-induced cyclization of 2-(2-(arylethynyl)benzylidene)malononitrile derivatives with 2,6-di(tert-butyl)-4-met...A green and highly efficient strategy for the preparation of bridged spirocyclic compounds via visible-light-induced cyclization of 2-(2-(arylethynyl)benzylidene)malononitrile derivatives with 2,6-di(tert-butyl)-4-methylphenol(BHT)at room temperature was developed.The photoinduced radical reactions generated the corresponding products in good yields under simple and mild reaction conditions.展开更多
Dyes endowed with aggregation-induced emission(AIE)properties represent a very significant class of chromophores.Nonetheless,current AIE dyes have yet to possess a readily tunable fluorescence switching mechanism.Here...Dyes endowed with aggregation-induced emission(AIE)properties represent a very significant class of chromophores.Nonetheless,current AIE dyes have yet to possess a readily tunable fluorescence switching mechanism.Here,we delineate a structurally distinctive family of dyes,termed XD dyes,which exhibit AIE attributes.Notably,the novel XD dyes feature an intrinsic helical cyclization as a tunable fluorescence switch,conferring them with an advantage over conventional AIE fluorophores.Initially,the fluorescence of the XD dyes in water-tetrahydrofuran mixtures was investigated through spectral analysis as the volume of the aqueous component increased.Subsequently,particle size analysis,in conjunction with scanning electron microscopy(SEM),was employed to substantiate the aggregation propensity of the XD dyes.Of particular significance,XD-4 was observed for the first time to exhibit pronounced solid-state fluorescence,thereby corroborating the XD dyes'capacity for robust fluorescence emission in the aggregated state.Moreover,alterations in optical properties and aggregation behavior of the XD dyes were elucidated theoretically through quantum chemical computations and molecular dynamics simulations.Critically,the calculated reorganization energy of XD-4 was reduced in an aqueous medium was reduced compared to the gas phase,providing further confirmation of its AIE nature.The unique AIE characteristics of the XD dyes were validated through the integration of experimental data and theoretical insights,offering novel perspectives for the advancement of highperformance fluorescent dyes and probes.展开更多
Herein,we disclose a highly regio-/chemoselective tandem asymmetric dearomatized halofunctionalization reaction of phenoltethered ynamides with diverse electrophilic halogenation sources in a catalyst-free manner for ...Herein,we disclose a highly regio-/chemoselective tandem asymmetric dearomatized halofunctionalization reaction of phenoltethered ynamides with diverse electrophilic halogenation sources in a catalyst-free manner for the practical and rapid assembly of a series of halogenated spirocyclic enones.Besides,the related dearomatized selenation and protonation are also achieved,affording the corresponding selenated and protonated spirocycles in high efficiency.Moreover,the enantioselectivities of these products can be perfectly induced by Evans auxiliaries(99%ees).Significantly,this protocol not only represents the first tandem asymmetric halofunctionalization reaction of phenol derivatives,but also constitutes the first asymmetric halogenation/selenation of ynamides.Theoretical calculations indicate a remote induction model of Evans chiral auxiliary-attached keteniminium.展开更多
Stability against oxygen is an important factor affecting the performance of organic semiconductor devices.Improving photooxidation stability can prolong the service life of the device and maintain the mechanical and ...Stability against oxygen is an important factor affecting the performance of organic semiconductor devices.Improving photooxidation stability can prolong the service life of the device and maintain the mechanical and photoelectric properties of the device.Generally,various encapsulation methods from molecular structure to macroscopic device level are used to improve photooxidation stability.Here,we adopted a crystallization strategy to allow 14H-spiro[dibenzo[c,h]acridine-7,9′-fluorene](SFDBA)to pack tightly to resist fluorescence decay caused by oxidation.In this case,the inert group of SFDBA acts as a“steric armor”,protecting the photosensitive group from being attacked by oxygen.Therefore,compared with the fluorescence quenching of SFDBA powder under 2 h of sunlight,SFDBA crystal can maintain its fluorescence emission for more than 8 h under the same conditions.Furthermore,the photoluminescence quantum yields(PLQYs)of the crystalline film is 327%higher than that of the amorphous film.It shows that the crystallization strategy is an effective method to resist oxidation.展开更多
The difunctionalization of bicyclo[1.1.0]butanes is an under-explored transformation that accesses to moieties that are otherwise difficult to prepare.Herein,a new oxidative radical alkylarylation of N-aryl bicyclobut...The difunctionalization of bicyclo[1.1.0]butanes is an under-explored transformation that accesses to moieties that are otherwise difficult to prepare.Herein,a new oxidative radical alkylarylation of N-aryl bicyclobutyl amides with C(sp^(3))−H feedstocks is achieved in an atom-economic and photocatalyst-and light-free manner.This protocol follows a sequential C(sp^(3))–H/C(sp^(2))–H functionalization,providing an efficient route for diversity-oriented synthesis of functionalized 3-spirocyclobutyl oxindoles.In particular,a wide range of C(sp^(3))−H feedstocks,including ether,alcohol,amine,thioether,polychlorinated methane,silane,acetone,acetonitrile,toluene,and alkane are all suitable for the C(sp^(3))−H functionalization,demonstrating the broad applicability of this transformation.展开更多
The design of new ligands with high affinity and specificity against the targets of interest has been a central focus in drug discovery.As one of the most commonly used methods in drug discovery,the cyclization repres...The design of new ligands with high affinity and specificity against the targets of interest has been a central focus in drug discovery.As one of the most commonly used methods in drug discovery,the cyclization represents a feasible strategy to identify new lead compounds by increasing structural novelty,scaffold diversity and complexity.Such strategy could also be potentially used for the follow-on drug discovery without patent infringement.In recent years,the cyclization strategy has witnessed great success in the discovery of new lead compounds against different targets for treating various diseases.Herein,we first briefly summarize the use of the cyclization strategy in the discovery of new small-molecule lead compounds,including the proteolysis targeting chimeras(PROTAC)molecules.Particularly,we focus on four main strategies including fused ring cyclization,chain cyclization,spirocyclization and macrocyclization and highlight the use of the cyclization strategy in lead generation.Finally,the challenges including the synthetic intractability,relatively poor pharmacokinetics(PK)profiles and the absence of the structural information for rational structure-based cyclization are also briefly discussed.We hope this review,not exhaustive,could provide a timely overview on the cyclization strategy for the discovery of new lead compounds.展开更多
基金the financial supports from the National Natural Science Foundation of China(Nos.22022111,21871257,21801240)the Natural Science Foundation of Fujian Province(No.2020J02008)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB20000000)。
文摘A visible-light-induced spirocyclizative hydroarylation via reductive dearomatization of a series of non activated arenes including 2-phenyl indoles and naphthalene derivatives under mild conditions is de scribed.An intriguing chemoselective dearomative hydroarylation of 2-phenyl indoles is presented.Th dearomative hydroarylation protocol rapidly delivers valuable spirocycles with carbon-carbon doub bonds from readily accessible aromatic precursors in a single step.
基金financial support from Jiangsu Planned Projects for Postdoctoral Research Funds(No.2018K293C)。
文摘A new method for the synthesis of 3-thioazaspiro[4,5]trienones was developed using Pd nanoparticle catalysts,which are highly efficient,environmentally friendly and recyclable.Alkynes and thiophene phenols are effectively cyclized by Pd/ZrO2 catalyst under visible light irradiation.The present protocol simply utilizes visible light as the safe and ecofriendly energy source,and the Pd/ZrO2 nanocomposite as photocatalyst provides a simple and practical approach to various 3-thioazaspiro[4,5]trienones in moderate conditions to high yields.
基金supported by the National Natural Science Foundation of China(No.22171046)the Hundred-Talent Project of Fujian(No.50021113).
文摘The development of efficient and sustainable methods to obtain spirocyclic compounds is of significance as these structures are widely found in pharmaceuticals and agrochemicals.Herein,we disclose an electrochemical dearomative spirocyclization of N-acyl sulfonamides in a continuous-flow cell.The reaction is simple and efficient without external catalysts or supporting electrolytes and could be applied in a decagram-scale synthesis.
基金the National Natural Science Foundation of China(22101075,U2004189)Central Plains Science and Technology Innovation Leader Project(224200510009)+1 种基金Postdoctoral Research Grant in Henan Province(202103085)Henan Key Laboratory of Organic Functional Molecules and Drug Innovation,and 111 Project(D17007)for financial support.
文摘Herein,we report a condition-controlled divergent synthesis of spiro indene-2,1'-isoindolinones and spiro isochroman-3,1'-isoindolinones through cobalt-catalyzed formal[4+1]and[4+1+1]spirocyclization of aromatic amides with 2-diazo-1H-indene-1,3(2H)-dione.When the reaction is carried out under air in ethyl acetate,spiro indene-2,1'-isoindolinones are formed through Co(II)-catalyzed C—H/N—H[4+1]spirocyclization.When the reaction is run under O2 in CH3CN,on the other hand,spiro isochroman-3,1'-isoindolinones are generated through Baeyer-Villiger oxidation of the in situ formed spiro indene-2,1'-isoindolinones with O2 as a cheaper and environmental-friendly oxygen source.In general,these protocols have advantages such as using non-precious and earth-abundant metal catalyst,no extra additive,high efficiency and regioselectivity.A gram-scale synthesis and the removal of the directing group further highlight its utility.
基金We are grateful for the financial support from 111 Project(No.B18035)and“the Fundamental Research Funds for the Central Universities”.
文摘Transition-metal-catalyzed cross-coupling reactions as very efficient and atom-economical approaches have been widely used to build up complex heterocyclic compounds.However,modification of 2-oxyl benzimidazole skeleton using maleimide compounds via C–H activation has remained unprecedented.Herein,we developed a rhodium(III)-catalyzed[5+1]cascade spiroannulation to construct diversified novel benzimidazole-incorporated spirosuccinimide derivatives from 2-oxyl benzimidazoles and maleimides.
基金supported by the program of research fund for returning scholars of Ministry of Education of China(No.200812)the Open Foundation of Chemical Engineering Subject(No.200903),Qingdao University of Science & Technology,China
文摘A new synthesis of spirocyclic oxindole analogue spiro[piperidine-4,3＇-pyrrolol2,3-b]pyridin]-2＇（1＇H）-one 1 is described. The key steps involve dialkylation of arylacetonitrile and cyclization of the azaoxindole ring by an intramolecular Buchwald-Hartwig amidation of carboxylic amide and aryl chloride. A small library was obtained by reductive amination of 1 with various aldehydes and was screened against human lung cancer cell A549, human liver cancer cell BEL7402, and human colon cancer cell HCT-8. The results show that most of the library compounds 2 have some inhibitory activities. 2-（Trifluoromethoxy） benzylic substituted spirocyclic azaoxindole 2e was identified as a nanomolar inhibitor against human lung cancer cell A-549 （IC50 = 50 nmol/L）.
基金supported by the National Natural Science Foundation of China(No.82204276)the Guangxi Natural Science Foundation(No.2021GXNSFBA075036)+4 种基金the Specific Research Project of Guangxi for Research Bases and Talents(Nos.AD22035018,AD20297036)the 2021 University-Level Scientific Research Projects of Guangxi Minzu University(No.2021MDKJ003)the Talent Scientific Research Initiation Project of Guangxi Minzu University(No.2021KJQD09)the Xiangsi Lake Youth Innovation Team Project of Guangxi Minzu University(No.2021 RSCXSHQN01)the Guangxi Scholarship Fund of Guangxi Education Department.
文摘One new spirocyclic alkaloid,5-isopentenyl-cryptoechinuline D(1),along with 11 known compounds(2–12),were iso-lated from a marine fungus Aspergillus ruber TX-M4-1.The structures of compounds 1–12 were elucidated by spectroscopic evi-dences.Compound 1 was initially isolated as an enantiomer,and further separation of 1 by chiral HPLC afforded a pair of enantio-mers,including(-)-5-isopentenyl-cryptoechinuline D(1a)and(+)-5-isopentenyl-cryptoechinuline D(1b).Their absolute configura-tions were elucidated by ECD spectroscopic data.Compounds 1a,5 and 10 could inhibit thioredoxin reductase(TrxR)activity with IC50 values of 6.2,36.3 and 18.6μmol L^(-1),respectively.Surface plasmon resonance(SPR)study also demonsrated the interactions between compounds 6,8 and Niemann-Pick C1 Like 1(NPC1L1)respectively,which indicate that compounds 6 and 8 are potential NPC1L1 inhibitors.
基金Project supported by the National Natural Science Foundation of China(No.21162008)
文摘A novel spiro-compound（C20 H15 N2 O3 P） has been synthesized and characterized by means of IR and 1H NMR. Its crystal structure was determined by X-ray diffractometry. The crystal belongs to the monoclinic system, space group P21 /c with a = 9.1628（7）, b = 12.9490（7）, c = 15.7898（11）, β = 103.952（8）o, Mr = 36.08, V = 1818.2（2）3, Z = 4, Dc = 1.382 g/cm3, F（000） = 788, μ = 0.179 mm-1, R = 0.0701 and wR = 0.1513. The preliminary biological test showed that the title compound has activities against Escherichia coli, S.albus, Bacillus subtilis, Staphylocc- ocusaureus and Micrococcus tetragenus with MIC to be 0.038, 0.038, 0.075, 2.48, and 0.15 mg/mL, respectively.
基金supported by the National Natural Science Foundation of China(Nos. 21372256, 21572264)
文摘The double [3 + 2] cycloaddition of allenoates with nitrile oxides is presented. The reaction worked well under mild reaction conditions to give the spirobidihydroisoxazole in moderate to excellent yields with excellent diastereoselectivities. The two dihydroisoxazole rings have been formed via a sequential double [3 + 2] cycloaddition.
基金supported by the National Natural Science Foundation of China(No.30472079)National Basic Research Program of China(No.2006CB504100)
文摘The present study aimed at identifying cell cycle inhibitors from the fermentation broth of Streptomyces pseudoverticillus YN17707. Activity-guided isolation was performed on ts FT210 cells. Compounds were isolated through various chromatographic methods and elucidated by spectroscopic analyses. Flow cytometry was used to evaluate the cell cycle inhibitory activities of the fractions and compounds. Two compounds were obtained and identified as pteridic acid hydrate(1) and pteridic acid C(2), which arrested the ts FT210 cells at the G0/G1 phase with the MIC values being 32.8 and 68.9 μmol·L-1, respectively. These results provide a basis for future development of Compounds 1 and 2 as novel cell cycle inhibitors for cancer therapy.
基金financially supported by the NSFC-Joint Foundation of Yunnan Province(No.U1902213)the Second Tibetan Plateau Scientific Expedition and Research(STEP)Program(No.2019QZKK0502020303)+1 种基金Southeast Asia Biodiversity Research Institute,CAS(No.2017CASSEABRIQG003)the Natural Sciences Foundation of Yunnan Province(No.2019FA003)。
文摘Spirohypatone A(1),a spirocyclic PPAP(polycyclic polyprenylated acylphloroglucinol) bearing an unprecedented hexahydro-1’H-spiro[cyclohexane-1,2’-pentalene]-2,4,6-trione core and a new homologue(spirohypatone B,2) were isolated from Hypericum patulum together with two known biosynthetic precursors.Compound 1 represents the first spirocyclic PPAP possessing a 5/5/6 carbon ring system,biogenetically derived from the intermediate 3(attack from C-3 to C-12),which was differed from normal spirocyclic PPAPs(attack from C-3 to C-11).In addition,through extensive spectroscopic analysis,an interconversion mechanism of keto-enol of 1 was postulated and confirmed by its methylated reaction.The structures and absolute configurations of 1 and 2 were determined by comprehensive spectroscopic and chemical derivatized methods and X-ray crystallography.Compounds 1,2,and 4 were tested to exhibit cytotoxic activities against several cancer cell lines.
基金the National Natural Science Foundation of China (Nos.21572051,21602057,21901071,and 21971061)Natural Science Foundation of Hunan Province (Nos.2020JJ5350 and 2020JJ5347)+1 种基金Scientific Research Fund of Hunan ProvincialEducation Department (Nos.18A002,19B359 and 17C1137)Science and Technology Planning Project of Hunan Province (No. 2018TP1017) for financial support。
文摘A simultaneous C2-H arylation and C8-H alkylation of naphthalene ring has been achieved by palladiumcatalyzed cascade reaction of N-(2-halophenyl)-2-(naphthalen-1-yl)acrylamides with aryl iodides,which provides an efficient method for synthesizing various aryl-substituted spirocyclic oxindoles.The protocol enables three C-C bonds formation via an intramolecular Heck reaction and sequentially regioselective C-H bond activation.
基金supported by the National Natural Science Foundation of China (No.21001016 and 20901009)
文摘Aminosilane bearing bulky substituents on nitrogen： LH2 （L = Me2Si（NDipp＇）2, Dipp = 2,6-diisopropylphenyl） was reacted with BuLi in toluene. The resulting bulky chelating dianion Me2Si（NDipp）2 was used to synthesize the unusual spirocyclic heterotriatomic complex [MeESi（NDipp）2]ESn （1） by its reaction with SnCl4 and the bulky heterotriatomic complex Me2Si（NDipp）2SnPh2 （2） with Ph2SnC12. 1 belongs to the monoclinic system, space group P21/n with a = 13.193（2）, b = 20.663（3）, c = 20.403（3）A, β = 99.954（2）°, V = 5478.3（15） A3, C55H85.5N4Si2Sn, Mr = 977.64, Z = 4, Dc. = 1.185 Mg/m3, μ（MoKa） = 0.547 mm-1, F（000） = 2086, S = 1.000, the final R = 0.0614 and wR = 0.1322 for 14446 observed reflections （1 〉 2σ（I）） and R = 0.0797 and wR = 0.1456 for all data. 2 belongs to the triclinic system, space group P1 with a = 10.36（15）, b = 13.204（7）, c = 14.363（7） A, a = 90.214（10）, β = 106.182（7）, y = 109.854（8）°, V = 1764.4（15） A3, C38HsoN2SiSn, M,. = 681.58, Z = 2, Dc = 1.283 Mg/m^3,μ（MoKa） = 0.785 mm-1, F（000） = 712, S = 1.002, the final R = 0.0498 and wR = 0.0955 for 7533 observed reβections （I 〉 2σ（I）） and R = 0.0676 and wR = 0.1018 for all data. In the structure of 1, the tin atom is located in the spirocyclic center of the two fused four-membered SnN2Si rings. The two complexes were characterized by ^1H NMR, elemental analysis, and single-crystal X-ray structural analysis.
文摘A simple and direct method for preparation of N-substituted spirocyclic dieSter of □-amino phosphonic acid (4) in high yield is introduced. The reaction consists of the threecomponent reachon of phenylurea (1), an aromatic aldehyde (2), and 3,9-dichloro-2,4,8,10-tetraoxa- 3, 9 -diphosphaspiro [5,5] undecane (3) in anhydrous benzene.
基金the National Natural Science Foundation of China (No. 22071171)the Natural Science Foundation of Zhejiang Province (No. LZ22B020003)
文摘A green and highly efficient strategy for the preparation of bridged spirocyclic compounds via visible-light-induced cyclization of 2-(2-(arylethynyl)benzylidene)malononitrile derivatives with 2,6-di(tert-butyl)-4-methylphenol(BHT)at room temperature was developed.The photoinduced radical reactions generated the corresponding products in good yields under simple and mild reaction conditions.
基金supported by the National Natural Science Foundation of China(22277014,22077048)the Guangxi Natural Science Foundation(AD21220061,2021GXNSFDA075003)+2 种基金the Startup Fund of Guangxi University(A3040051003)the financial support from the National Research Foundation of Republic of Korea(CRI Project No.2018R1A3B1052702,J.S.K)the University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering,Henan Normal University(2020ZD01)for support。
文摘Dyes endowed with aggregation-induced emission(AIE)properties represent a very significant class of chromophores.Nonetheless,current AIE dyes have yet to possess a readily tunable fluorescence switching mechanism.Here,we delineate a structurally distinctive family of dyes,termed XD dyes,which exhibit AIE attributes.Notably,the novel XD dyes feature an intrinsic helical cyclization as a tunable fluorescence switch,conferring them with an advantage over conventional AIE fluorophores.Initially,the fluorescence of the XD dyes in water-tetrahydrofuran mixtures was investigated through spectral analysis as the volume of the aqueous component increased.Subsequently,particle size analysis,in conjunction with scanning electron microscopy(SEM),was employed to substantiate the aggregation propensity of the XD dyes.Of particular significance,XD-4 was observed for the first time to exhibit pronounced solid-state fluorescence,thereby corroborating the XD dyes'capacity for robust fluorescence emission in the aggregated state.Moreover,alterations in optical properties and aggregation behavior of the XD dyes were elucidated theoretically through quantum chemical computations and molecular dynamics simulations.Critically,the calculated reorganization energy of XD-4 was reduced in an aqueous medium was reduced compared to the gas phase,providing further confirmation of its AIE nature.The unique AIE characteristics of the XD dyes were validated through the integration of experimental data and theoretical insights,offering novel perspectives for the advancement of highperformance fluorescent dyes and probes.
基金supported by the National Natural Science Foundation of China(22125108 and 22121001 for Ye LW,22122109 and 22271253 for Hong X)the National Key R&D Program of China(2022YFA1504301,Hong X)+8 种基金the Zhejiang Provincial Natural Science Foundation of China(LDQ23B020002,Hong X)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SNZJU-SIAS-006,Hong X)the Beijing National Laboratory for Molecular Sciences(BNLMS202102,Hong X)the CAS Youth Interdisciplinary Team(JCTD-2021-11,Hong X)the Fundamental Research Funds for the Central Universities(226-2022-00140,226-2022-00224,and 226-2023-00115,Hong X)the State Key Laboratory of Physical Chemistry of Solid Surfaces(202210,Hong X)the Leading Innovation Team grant from the Department of Science and Technology of Zhejiang Province(2022R01005,Hong X)the Natural Science Foundation of Jiangsu Province(BK20211059)National Found for Fostering Talents of Basic Science(NFFTBS,J1310024).
文摘Herein,we disclose a highly regio-/chemoselective tandem asymmetric dearomatized halofunctionalization reaction of phenoltethered ynamides with diverse electrophilic halogenation sources in a catalyst-free manner for the practical and rapid assembly of a series of halogenated spirocyclic enones.Besides,the related dearomatized selenation and protonation are also achieved,affording the corresponding selenated and protonated spirocycles in high efficiency.Moreover,the enantioselectivities of these products can be perfectly induced by Evans auxiliaries(99%ees).Significantly,this protocol not only represents the first tandem asymmetric halofunctionalization reaction of phenol derivatives,but also constitutes the first asymmetric halogenation/selenation of ynamides.Theoretical calculations indicate a remote induction model of Evans chiral auxiliary-attached keteniminium.
基金supported by the Natural Science Foundation of Nanjing University of Posts and Telecommunications(NY222157,NY221085)State Key Laboratory of Organic Electronics and Information Display(GZR2022010008)+5 种基金Key Laboratory of Low-dimensional Materials Chemistry of Jiangsu Province(JSKC20022)General Program of China Postdoctoral Science Foundation(2022M711684)General Program of Basic Science(Natural Science)of Colleges and Universities of Jiangsu Province(22KJB430036)National Overseas Study Fund(202008320051)National Key Laboratory(2009DS690095)the National Natural Science Foundation of China(62288102).
文摘Stability against oxygen is an important factor affecting the performance of organic semiconductor devices.Improving photooxidation stability can prolong the service life of the device and maintain the mechanical and photoelectric properties of the device.Generally,various encapsulation methods from molecular structure to macroscopic device level are used to improve photooxidation stability.Here,we adopted a crystallization strategy to allow 14H-spiro[dibenzo[c,h]acridine-7,9′-fluorene](SFDBA)to pack tightly to resist fluorescence decay caused by oxidation.In this case,the inert group of SFDBA acts as a“steric armor”,protecting the photosensitive group from being attacked by oxygen.Therefore,compared with the fluorescence quenching of SFDBA powder under 2 h of sunlight,SFDBA crystal can maintain its fluorescence emission for more than 8 h under the same conditions.Furthermore,the photoluminescence quantum yields(PLQYs)of the crystalline film is 327%higher than that of the amorphous film.It shows that the crystallization strategy is an effective method to resist oxidation.
基金funded by National Natural Science Foundation of China(No.22201070).
文摘The difunctionalization of bicyclo[1.1.0]butanes is an under-explored transformation that accesses to moieties that are otherwise difficult to prepare.Herein,a new oxidative radical alkylarylation of N-aryl bicyclobutyl amides with C(sp^(3))−H feedstocks is achieved in an atom-economic and photocatalyst-and light-free manner.This protocol follows a sequential C(sp^(3))–H/C(sp^(2))–H functionalization,providing an efficient route for diversity-oriented synthesis of functionalized 3-spirocyclobutyl oxindoles.In particular,a wide range of C(sp^(3))−H feedstocks,including ether,alcohol,amine,thioether,polychlorinated methane,silane,acetone,acetonitrile,toluene,and alkane are all suitable for the C(sp^(3))−H functionalization,demonstrating the broad applicability of this transformation.
基金This work is supported by the National Natural Science Foundation of China(Nos.22277110,81973177 and 31900875,China)the Natural Science Foundation of Henan Province(Nos.222300420069 and 222301420049,China)Program for Science&Technology Innovation Talents in Universities of Henan Province(No.21HASTIT045,China).
文摘The design of new ligands with high affinity and specificity against the targets of interest has been a central focus in drug discovery.As one of the most commonly used methods in drug discovery,the cyclization represents a feasible strategy to identify new lead compounds by increasing structural novelty,scaffold diversity and complexity.Such strategy could also be potentially used for the follow-on drug discovery without patent infringement.In recent years,the cyclization strategy has witnessed great success in the discovery of new lead compounds against different targets for treating various diseases.Herein,we first briefly summarize the use of the cyclization strategy in the discovery of new small-molecule lead compounds,including the proteolysis targeting chimeras(PROTAC)molecules.Particularly,we focus on four main strategies including fused ring cyclization,chain cyclization,spirocyclization and macrocyclization and highlight the use of the cyclization strategy in lead generation.Finally,the challenges including the synthetic intractability,relatively poor pharmacokinetics(PK)profiles and the absence of the structural information for rational structure-based cyclization are also briefly discussed.We hope this review,not exhaustive,could provide a timely overview on the cyclization strategy for the discovery of new lead compounds.
