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 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
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
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
Catalyst innovation lies at the heart of transition-metal-catalyzed reaction development. In this article, we have explored the C(sp2)–H alkenylation activity with novel spirocyclic N-heterocyclic carbene(NHC)-based ...Catalyst innovation lies at the heart of transition-metal-catalyzed reaction development. In this article, we have explored the C(sp2)–H alkenylation activity with novel spirocyclic N-heterocyclic carbene(NHC)-based cyclometalated ruthenium pincer catalyst system, SNRu-X. After screening catalyst and condition, a high valent Ru(Ⅳ) dioxide(X = O_(2)) species has demonstrated superior reactivity in the catalytic alkenylation of aromatic and olefinic C–H bonds with unactivated alkenyl bromides and triflates. This reaction has achieved the easy construction of a wide range of(hetero)aromatic alkenes and dienes, in good to excellent yields with exclusive selectivity. Preliminary mechanistic studies indicate that this reaction may proceed through a single electron transfer(SET) triggered oxidative addition, by doing so, providing valuable complementary to classical alkenylation reactions that are dependent on activated alkenyl precursors.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
Visible-light-induced reductive dearomatization of nonactivated arenes is a very challenging transformation and remains in its infancy.Herein,we report a novel strategy to achieve a visible-light-induced spirocyclizat...Visible-light-induced reductive dearomatization of nonactivated arenes is a very challenging transformation and remains in its infancy.Herein,we report a novel strategy to achieve a visible-light-induced spirocyclizative remote arylcarboxylation of nonactivated arenes including naphthalenyl-and phenyl-bearing aromatics with CO_(2) under mild conditions through a radical-polar crossover cascade(RPCC).This reductive dearomatization protocol rapidly delivers a broad range of spirocyclic and valuable carboxylic acid derivatives from readily accessible aromatic precursors with generally good regioselectivity and chemoselectivity.展开更多
Objective To study the chemical constituents from the aerial parts of Hypericum beani/. Methods Various chromatographic techniques were used to separate the constituents and their structures were elucidated on the bas...Objective To study the chemical constituents from the aerial parts of Hypericum beani/. Methods Various chromatographic techniques were used to separate the constituents and their structures were elucidated on the basis of extensive spectroscopic interpretation. Results Fifteen compounds were isolated from the aerial parts of H. beanii. Their structures were identified as hyperbeanol E (1), (E)-Iinalool-l-oic acid (2), (4S,5R)-5-(4'-methyl-3'-pentenyl)-4-hydroxy-5-methyl- dihydrofuran-2-one (3), benzoic acid (4), 4-(3-O-3")-3"-methylbutenyl-6-phenyl- pyran-2-one (5), 4-hydroxy-4a,7-dimethoxy-4,4a-dihydrodibenzo-p-dioxJn-2(3H)- one (6), isoimperatorin (7), 2,3-dimethoxyxanthone (8), 3,4-dihydroxy-2- methoxyxanthone (9), osajaxanthone (10), nigrolineaxanthone F (1 1), hypercohone G (12), betulinic acid (1 3), oleanolic acid 3.13-caffeate (14), and isoastilbin (1 5). Conclusion Compound 1 is a new menthane monoterpene derivative which owns an extra lactone ring. Compounds 2-7 and 10-1 5 are isolated from genus Hypericum Linn. for the first time and the other compounds are first obtained from the plants in H. beanii.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
In this work, we designed and synthesized a novel spirocyclic compound functionalized spiro[fluorene-9,9'- xanthene] with carbazole group (2-carbazolyl-spiro[fluorene-9,9'-xanthene], SFX-Cz) via Friedel-Crafts and...In this work, we designed and synthesized a novel spirocyclic compound functionalized spiro[fluorene-9,9'- xanthene] with carbazole group (2-carbazolyl-spiro[fluorene-9,9'-xanthene], SFX-Cz) via Friedel-Crafts and Ullmann reaction, which is expected to own high thermal and morphological stability, and good carrier injection/ transporting properties due to the excellent hole transporting characteristics of carbazole and cruciform structure of spiro[fluorene-9,9'-xanthene]. The carbazole end-capped spiro[fluorene-9,9'-xanthene] SFX-Cz based PhOLEDs with Flrpic as phosphor emitter have been researched by varying dopant concentration, which exhibit the maximum EQEs of 8.9%, 7.4%, 9.1%, and 4.7% with the doping increasing from 10% to 50%. The higher performance PhOLEDs are independent on concentration variation from 10% to 30%, which suggests the bulky steric hindrance of SFX-Cz might be a potential canditate for high performance and inexpensive device with simplified process.展开更多
In order to develop novel spirocyclic tetronic acid lead compounds,a series of new spirocyclic tetronic acid derivatives containing oxime ether moiety was synthesized and bioassayed.The stmctures of 16 target compound...In order to develop novel spirocyclic tetronic acid lead compounds,a series of new spirocyclic tetronic acid derivatives containing oxime ether moiety was synthesized and bioassayed.The stmctures of 16 target compounds were characterized by lH NMR spectra,13C NMR spectra and high-resolution mass spectrometer(HRMS).Preliminary bioassays indicated that most of the title compounds displayed excellent insecticidal activity against Aphis fabae and Nilapmyata lugens at 100 mg/L.In particular,compound 6k showed the similar activity(LC50=6.87 mg/L)against A.fabae as the spirotetramat(LC50=4.56 mg/L)and had better efIects(LC50=l.64 mg/L)against N.lugens in comparison with spirotetramat(LC5o=7.90 mg/L).The study showed that compound 6k exhibited more promising and broad-spectrum insecticide activity and may serve as a new insecticidal agent for sucking pests.展开更多
A new type of dianionic Ir(Ⅲ) CCC pincer complexes(SNHC-Ir, 1a–1c) is successfully designed and synthesized by developing a one-step methodology, which involves an initial coordination of Ir(I) with the NHC and subs...A new type of dianionic Ir(Ⅲ) CCC pincer complexes(SNHC-Ir, 1a–1c) is successfully designed and synthesized by developing a one-step methodology, which involves an initial coordination of Ir(I) with the NHC and subsequent metallation of double sp2C–H bonds. This method is considerably useful over those reported by using strong coordination ligand or carbonic anion exchange,and would provide an alternative efficient template of organometallics synthesis. Experimental and density functional theory(DFT) calculation results indicate that the spirocyclic framework is a favourable factor for the facile formation and stabilization of these complexes. Primary investigation shows that chloride 1b can well catalyze homo and hetero addition of styrene derivatives and remote olefin isomerization, which represents the first catalytic application of the dianionic CCC pincer complexes.展开更多
Although the NHC-catalyzed cyclization reactions have been well established for the synthesis of various heterocycles,the corresponding all carbon cyclization reaction for the synthesis of carbocycles is far less esta...Although the NHC-catalyzed cyclization reactions have been well established for the synthesis of various heterocycles,the corresponding all carbon cyclization reaction for the synthesis of carbocycles is far less established.In this note,the NHC-catalyzed all carbon[4+2]cyclocondensation of α,β-unsaturated acyl chlorides and 3-alkenyloxindoles was developed to give the corresponding spirocarbocyclic oxindoles in good yield with good to high diastereoselectivities.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
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.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 (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suported by the National Natural Science Foundation of China (2187,1117, 91956203)the “111” Program of Minister of Education, Beijing National Laboratory for Molecular Sciences (BNLMS202109)the Science and Technology Commission of Shanghai Municipality (19JC1430100)。
文摘Catalyst innovation lies at the heart of transition-metal-catalyzed reaction development. In this article, we have explored the C(sp2)–H alkenylation activity with novel spirocyclic N-heterocyclic carbene(NHC)-based cyclometalated ruthenium pincer catalyst system, SNRu-X. After screening catalyst and condition, a high valent Ru(Ⅳ) dioxide(X = O_(2)) species has demonstrated superior reactivity in the catalytic alkenylation of aromatic and olefinic C–H bonds with unactivated alkenyl bromides and triflates. This reaction has achieved the easy construction of a wide range of(hetero)aromatic alkenes and dienes, in good to excellent yields with exclusive selectivity. Preliminary mechanistic studies indicate that this reaction may proceed through a single electron transfer(SET) triggered oxidative addition, by doing so, providing valuable complementary to classical alkenylation reactions that are dependent on activated alkenyl precursors.
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.
基金the financial support from NSFC(grant nos.21871257,22022111,and 21801240)the Natural Science Foundation of Fujian Province(grant no.2020J02008)the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDB20000000).
文摘Visible-light-induced reductive dearomatization of nonactivated arenes is a very challenging transformation and remains in its infancy.Herein,we report a novel strategy to achieve a visible-light-induced spirocyclizative remote arylcarboxylation of nonactivated arenes including naphthalenyl-and phenyl-bearing aromatics with CO_(2) under mild conditions through a radical-polar crossover cascade(RPCC).This reductive dearomatization protocol rapidly delivers a broad range of spirocyclic and valuable carboxylic acid derivatives from readily accessible aromatic precursors with generally good regioselectivity and chemoselectivity.
基金National Natural Science Foundation of China(31300293,81422046)General Project of Applied Foundation Research,Yunnan Province(2013FB067)+2 种基金Basic Research Project of Ministry of Science and Technology of China(2012FY110300)Major State Basic Research Development Program(2010CB951704)Youth Innovation Promotion Association CAS and SRF for ROCS,SEM to WL.Xiao
文摘Objective To study the chemical constituents from the aerial parts of Hypericum beani/. Methods Various chromatographic techniques were used to separate the constituents and their structures were elucidated on the basis of extensive spectroscopic interpretation. Results Fifteen compounds were isolated from the aerial parts of H. beanii. Their structures were identified as hyperbeanol E (1), (E)-Iinalool-l-oic acid (2), (4S,5R)-5-(4'-methyl-3'-pentenyl)-4-hydroxy-5-methyl- dihydrofuran-2-one (3), benzoic acid (4), 4-(3-O-3")-3"-methylbutenyl-6-phenyl- pyran-2-one (5), 4-hydroxy-4a,7-dimethoxy-4,4a-dihydrodibenzo-p-dioxJn-2(3H)- one (6), isoimperatorin (7), 2,3-dimethoxyxanthone (8), 3,4-dihydroxy-2- methoxyxanthone (9), osajaxanthone (10), nigrolineaxanthone F (1 1), hypercohone G (12), betulinic acid (1 3), oleanolic acid 3.13-caffeate (14), and isoastilbin (1 5). Conclusion Compound 1 is a new menthane monoterpene derivative which owns an extra lactone ring. Compounds 2-7 and 10-1 5 are isolated from genus Hypericum Linn. for the first time and the other compounds are first obtained from the plants in H. beanii.
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).
文摘In this work, we designed and synthesized a novel spirocyclic compound functionalized spiro[fluorene-9,9'- xanthene] with carbazole group (2-carbazolyl-spiro[fluorene-9,9'-xanthene], SFX-Cz) via Friedel-Crafts and Ullmann reaction, which is expected to own high thermal and morphological stability, and good carrier injection/ transporting properties due to the excellent hole transporting characteristics of carbazole and cruciform structure of spiro[fluorene-9,9'-xanthene]. The carbazole end-capped spiro[fluorene-9,9'-xanthene] SFX-Cz based PhOLEDs with Flrpic as phosphor emitter have been researched by varying dopant concentration, which exhibit the maximum EQEs of 8.9%, 7.4%, 9.1%, and 4.7% with the doping increasing from 10% to 50%. The higher performance PhOLEDs are independent on concentration variation from 10% to 30%, which suggests the bulky steric hindrance of SFX-Cz might be a potential canditate for high performance and inexpensive device with simplified process.
基金Supported by the National Key Research&Development Program of China(No.2017YFDO2OO5O5)the Natural Science Foundation of Zhejiang Province,China(No.LY 19C140006).
文摘In order to develop novel spirocyclic tetronic acid lead compounds,a series of new spirocyclic tetronic acid derivatives containing oxime ether moiety was synthesized and bioassayed.The stmctures of 16 target compounds were characterized by lH NMR spectra,13C NMR spectra and high-resolution mass spectrometer(HRMS).Preliminary bioassays indicated that most of the title compounds displayed excellent insecticidal activity against Aphis fabae and Nilapmyata lugens at 100 mg/L.In particular,compound 6k showed the similar activity(LC50=6.87 mg/L)against A.fabae as the spirotetramat(LC50=4.56 mg/L)and had better efIects(LC50=l.64 mg/L)against N.lugens in comparison with spirotetramat(LC5o=7.90 mg/L).The study showed that compound 6k exhibited more promising and broad-spectrum insecticide activity and may serve as a new insecticidal agent for sucking pests.
基金This work was supported by the National Natural Science Foundation of China(21502080,21772076,21871117,21772071,21702136,91956203)the“111”Program of Ministry of Education of China,the Major Project(2018ZX09711001-005-002)of Ministry of Science and Technology of China+2 种基金the Science and Technology Commission of Shanghai Municipality(19IC1430100)This work was supported by the High-Performance Computing Center of Shanghai Jiao Tong UniversityAlso,we thank Prof.Qing-Wei Zhang from the University of Science and Technology of China for his helpful discussion.
文摘A new type of dianionic Ir(Ⅲ) CCC pincer complexes(SNHC-Ir, 1a–1c) is successfully designed and synthesized by developing a one-step methodology, which involves an initial coordination of Ir(I) with the NHC and subsequent metallation of double sp2C–H bonds. This method is considerably useful over those reported by using strong coordination ligand or carbonic anion exchange,and would provide an alternative efficient template of organometallics synthesis. Experimental and density functional theory(DFT) calculation results indicate that the spirocyclic framework is a favourable factor for the facile formation and stabilization of these complexes. Primary investigation shows that chloride 1b can well catalyze homo and hetero addition of styrene derivatives and remote olefin isomerization, which represents the first catalytic application of the dianionic CCC pincer complexes.
基金Financial support from National Natural Science Foundation of China(No.21272237)the Ministry of Science and Technology of China(No.2011CB808600)the Chinese Academy of Sciences is gratefully acknowledged.
文摘Although the NHC-catalyzed cyclization reactions have been well established for the synthesis of various heterocycles,the corresponding all carbon cyclization reaction for the synthesis of carbocycles is far less established.In this note,the NHC-catalyzed all carbon[4+2]cyclocondensation of α,β-unsaturated acyl chlorides and 3-alkenyloxindoles was developed to give the corresponding spirocarbocyclic oxindoles in good yield with good to high diastereoselectivities.
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.