1-Substituted 1,2,3-triazoles represents‘privileged’structural scaffolds of many clinical pharmaceuticals.However,the traditional methods for their preparation mainly rely on thermal[3+2]cycloaddition of potentially...1-Substituted 1,2,3-triazoles represents‘privileged’structural scaffolds of many clinical pharmaceuticals.However,the traditional methods for their preparation mainly rely on thermal[3+2]cycloaddition of potentially dangerous acetylene and azides.Here we report a base-mediated[4+1]annulation of azoalkenes generated in situ from readily available difluoroacetaldehyde N-tosylhydrazones(DFHZ-Ts)with amines under relatively mild conditions.This azide-and acetylene-free strategy provides facile access to diverse 1-substituted 1,2,3-triazole derivatives in high yield in a regiospecific manner.This transformation has great functional group tolerance and can suit a broad substrate scope.Furthermore,the application of this novel methodology in the gram-scale synthesis of an antibiotic drug PH-027 and in the late-stage derivatization of several bioactive small molecules and clinical drugs demonstrated its generality,practicability and applicability.展开更多
A new method to tetrahydro-β-carbolines(βCs) from tryptamine is described and the aromatization of THβCs to βCs by manganese dioxide is reported for the first time in this type of compounds.
A series of N1-substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyrazolethiocarboxamide were prepared from the Mannich bases of aryl ketones in good yields. Some derivatives were found to be active against the cysteine p...A series of N1-substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyrazolethiocarboxamide were prepared from the Mannich bases of aryl ketones in good yields. Some derivatives were found to be active against the cysteine protease of T.cruzi..展开更多
An efficient procedure for the preparation of 1-substituted-1H-1,2,3,4-tetrazoles via a three-component condensation of triethyl orthoformate, amine, and trimethylsilyl azide using inexpensive and environment-friendly...An efficient procedure for the preparation of 1-substituted-1H-1,2,3,4-tetrazoles via a three-component condensation of triethyl orthoformate, amine, and trimethylsilyl azide using inexpensive and environment-friendly FeCl3 as catalyst under solvent-free conditions has been reported. The reaction generates the corresponding 1-substituted tetrazole in excellent yields.展开更多
A series of novel 2-（1-substituted-1,11-undecylidene）-5-arylimino-△^3-1,3,4-thiadiazolines （4） were synthesized and their structure was characterized by ^1H NMR, ^13C NMR and elemental analysis. Their solubility ...A series of novel 2-（1-substituted-1,11-undecylidene）-5-arylimino-△^3-1,3,4-thiadiazolines （4） were synthesized and their structure was characterized by ^1H NMR, ^13C NMR and elemental analysis. Their solubility in both polar and non-polar solvents is significantly improved owing to the introduction of ethyl or methylthio group at cyclododecyl ring as compared with parent compounds [1, 2-（1,11-undecylidene）-5-arylimino-△^3-1,3,4-thiadiazolines]. However, their fungicidal activity against Rhizoctonia solani is less than that of parent compounds. X-ray diffraction analysis of a representative compound （4d） showed that the conformation of 12-membered ring is still [3333], in which the ethyl group present at the side-exo position and the thiadiazoline ring at the comer carbon. The thiadiazoline plane is perpendicular to the cyclododecyl one.展开更多
Using the ligand bis（3-（1H-imidazol-1-yl）-1-phenylpropan-1-one） L, two novel complexes [CuL2（ph））]·H2O 1 and [ZnL2（tp）] 2 （ph = phthalic acid, tp = terephthalic acid） have been synthesized and their cr...Using the ligand bis（3-（1H-imidazol-1-yl）-1-phenylpropan-1-one） L, two novel complexes [CuL2（ph））]·H2O 1 and [ZnL2（tp）] 2 （ph = phthalic acid, tp = terephthalic acid） have been synthesized and their crystal structures were determined by single-crystal X-ray diffraction analysis. Crystal data for 1： triclinic, space group P1^-, a = 9.4300（17）, b = 12.148（2）, c = 13.721（2） A, a = 109.620（2）,β = 94.351（2）, y = 94.830（2）°, C32H30N4O7Cu, Mr = 646.14, V= 1466.2（4） A^3, Z = 2, Dc = 1.464 g/cm3, It（MoKa） = 0.801 mm^-1, F（000） = 670, the final R = 0.0337 and wR = 0.0859 for 5122 observed reflections with I 〉 2σ（I）, And those for 2： monoclinic, space group P2/n, a = 7.1866（11）, b = 14.144（2）, c = 14.407（2）/k, β = 101.427（2）°, C32H28N4O6Zn, Mr = 629.95, V = 1435.4（4） A3, Z = 2, Dc = 1.457 g/cm3, μ（MoKa） = 0.908 mm^-1, F（000） = 652, the final R = 0.0438 and wR= 0.0821 for 2546 observed reflections with I〉 2σ（I）. In 1 and 2, ph or tp ligauds bridge the six-coordinated copper（Ⅱ） or four-coordinated zinc（Ⅱ） ions forming 1D zigzag chains while L ligands act as the terminal monodentate ligand. It is noted that weak non-classical C-H…O plays the important and dominating roles in the formation of 2D supramolecular architectures of 1, but in 2 non-classical C-H…O and aromatic π…π Stacking interactions are quite important and play dominant roles in the self-assembly of 2D supramolecular architectures.展开更多
A series of novel 5-（trifluoromethyl）-1H-pyrazole-4-carboxamide derivatives（6a–6n, 7a, 7b, and 8a-8f）were synthesised by placing the amide bond at the 4-position of the pyrazole ring. These derivatives differed f...A series of novel 5-（trifluoromethyl）-1H-pyrazole-4-carboxamide derivatives（6a–6n, 7a, 7b, and 8a-8f）were synthesised by placing the amide bond at the 4-position of the pyrazole ring. These derivatives differed from the structure of chlorantraniliprole analogues with the amide bond at the 5-position of the pyrazole ring. Preliminary bioassay results revealed that a few title compounds exhibited good insecticidal activities against lepidopteran pests, such as Plutella xylostella, Mythimna separate, Heliothis armigera, and Ostrinia nubilalis. Some title compounds also elicited broad-spectrum insecticidal activities against dipterous insects including Culex pipiens pallens after altering the amide position. Similar to pyrazole-5-carboxamide analogues, compounds 6b and 6e showed 100% insecticidal activity against P. xylostella, C. pipiens pallens, and M. separate at concentrations of 200, 2, and 200 mg/m L, respectively.This finding suggested that 5-（trifluoromethyl）-1H-pyrazole-4-carboxamide derivatives are potential alternative insecticides for management of agriculture pests.展开更多
A visible light-promoted fast photochemical Wolff rearrangement was developed toward synthesis ofα-substituted amides in continuous flow with the use of a photochemical oscillatory flow reactor(POFR).The control expe...A visible light-promoted fast photochemical Wolff rearrangement was developed toward synthesis ofα-substituted amides in continuous flow with the use of a photochemical oscillatory flow reactor(POFR).The control experiment indicates that a fast process of the Wolff rearrangement(<40 s)is involved.Notably,this protocol does not require excess use of any reactants,and the resultingα-substituted amides could be isolated by recrystallization in good to excellent yields.展开更多
Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development.The advantageous effects of covalent compounds compared with non...Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development.The advantageous effects of covalent compounds compared with non-covalent ones are highly dependent on electrophilic warheads.Hence,electrophilic warheads with tunable reactivity and selectivity are highly demanded in fields of medicinal chemistry and chemical biology.Herein,we report a novel electrophilic warhead,chloromethyl group activated by thiol-substituted 1,2,4-triazole.Interestingly,a pair of regioisomers could be simultaneously occurred in the step of alkylation during the synthesis of this unique motif.This is a rare example that the alkylation could simultaneously generate these two separable regioisomers of 1,2,4-triazole at the nitrogen or sulfur atom.The covalent-working mechanism of this new warhead is confirmed by various chemoproteomics experiments including target identification and binding site mapping.Importantly,the reactivity and selectivity of this new electrophilic warhead could be efficiently tuned by virtue of stereo effect.Interestingly,one pair of regioisomers(19S and 19X)induced distinct modes of cell death.Isomer 19S could induce apoptosis of colon cancer cells while 19X could induce both apoptosis and ferroptosis.Together,this study provides pairs of novel electrophilic warheads that could be useful not only in supporting the design of covalent compounds for drug discovery but also in providing chemical probes for the fundamental biological study.展开更多
Temperature plays a crucial role in regulating polymorphism in supramolecular polymers.Understanding the mechanism behind temperature-dependent supramolecular polymorphism is crucial as it provides an opportunity to t...Temperature plays a crucial role in regulating polymorphism in supramolecular polymers.Understanding the mechanism behind temperature-dependent supramolecular polymorphism is crucial as it provides an opportunity to tailor polymorphs for specific properties and applications.In this study,we present our findings on a naphthalimide-substituted benzene-1,3,5-tricarboxamide derivative,R-Nap-1,which exhibits two distinct polymerization pathways at varying temperatures.At 313 K,polymerization results in the formation of an M-chiral polymorph,whereas at 253 K,a P-chiral polymorph is formed.Both polymorphs are notably stable,remaining unchanged for over six months under ambient conditions.Theoretical calculations and experimental investigations allowed us to elucidate the mechanisms underlying these polymorphic transformations.The formation of the M-chiral polymorph at 313 K is attributed to the nucleation and growth of R-Nap-1 monomers once their concentration surpasses a critical threshold.Conversely,at lower temperatures(e.g.,253 K),the monomers undergo facile transformation into dimers due to a lower energy barrier and reduced Gibbs energy compared to the monomeric state.Subsequently,these dimers undergo nucleation-elongation to form the P-chiral polymorph when their concentration exceeds the critical polymerization concentration.The stability and lack of interconversion between the two polymorphs can be attributed to their close thermodynamic stabilities,as evidenced by variable-temperature CD spectra and DFT calculations.These findings highlight the importance of accurate temperature control in supramolecular polymerization processes,making a significant contribution to the understanding of supramolecular polymorphism,thus advancing the field of supramolecular chemistry.展开更多
基金supported by the National Natural Science Foundation of China(NSFC,Nos.21871043,21961130376)Department of Science and Technology of Jilin Province(Nos.20180101185JC,20190701012GH,20200801065GH)the Fundamental Research Funds for the Central Universities(Nos.2412019ZD001,2412020ZD003)。
文摘1-Substituted 1,2,3-triazoles represents‘privileged’structural scaffolds of many clinical pharmaceuticals.However,the traditional methods for their preparation mainly rely on thermal[3+2]cycloaddition of potentially dangerous acetylene and azides.Here we report a base-mediated[4+1]annulation of azoalkenes generated in situ from readily available difluoroacetaldehyde N-tosylhydrazones(DFHZ-Ts)with amines under relatively mild conditions.This azide-and acetylene-free strategy provides facile access to diverse 1-substituted 1,2,3-triazole derivatives in high yield in a regiospecific manner.This transformation has great functional group tolerance and can suit a broad substrate scope.Furthermore,the application of this novel methodology in the gram-scale synthesis of an antibiotic drug PH-027 and in the late-stage derivatization of several bioactive small molecules and clinical drugs demonstrated its generality,practicability and applicability.
基金Project supported by National Natural Science Foundation of China(No.2870083)
文摘A new method to tetrahydro-β-carbolines(βCs) from tryptamine is described and the aromatization of THβCs to βCs by manganese dioxide is reported for the first time in this type of compounds.
文摘A series of N1-substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyrazolethiocarboxamide were prepared from the Mannich bases of aryl ketones in good yields. Some derivatives were found to be active against the cysteine protease of T.cruzi..
文摘An efficient procedure for the preparation of 1-substituted-1H-1,2,3,4-tetrazoles via a three-component condensation of triethyl orthoformate, amine, and trimethylsilyl azide using inexpensive and environment-friendly FeCl3 as catalyst under solvent-free conditions has been reported. The reaction generates the corresponding 1-substituted tetrazole in excellent yields.
基金supports from the National Basic Research Program of China(No. 2003CB 114407)
文摘A series of novel 2-（1-substituted-1,11-undecylidene）-5-arylimino-△^3-1,3,4-thiadiazolines （4） were synthesized and their structure was characterized by ^1H NMR, ^13C NMR and elemental analysis. Their solubility in both polar and non-polar solvents is significantly improved owing to the introduction of ethyl or methylthio group at cyclododecyl ring as compared with parent compounds [1, 2-（1,11-undecylidene）-5-arylimino-△^3-1,3,4-thiadiazolines]. However, their fungicidal activity against Rhizoctonia solani is less than that of parent compounds. X-ray diffraction analysis of a representative compound （4d） showed that the conformation of 12-membered ring is still [3333], in which the ethyl group present at the side-exo position and the thiadiazoline ring at the comer carbon. The thiadiazoline plane is perpendicular to the cyclododecyl one.
基金Fund for Central Universities (ZXH2009D011)Natural Science Foundation of Tianjin (09JCYBJC04200)+1 种基金National Natural Science Foundation of China Civil Aviation Administration of China (61079010) Scientific Research Foundation of Civil Aviation University of China (2011KYS05)
文摘Using the ligand bis（3-（1H-imidazol-1-yl）-1-phenylpropan-1-one） L, two novel complexes [CuL2（ph））]·H2O 1 and [ZnL2（tp）] 2 （ph = phthalic acid, tp = terephthalic acid） have been synthesized and their crystal structures were determined by single-crystal X-ray diffraction analysis. Crystal data for 1： triclinic, space group P1^-, a = 9.4300（17）, b = 12.148（2）, c = 13.721（2） A, a = 109.620（2）,β = 94.351（2）, y = 94.830（2）°, C32H30N4O7Cu, Mr = 646.14, V= 1466.2（4） A^3, Z = 2, Dc = 1.464 g/cm3, It（MoKa） = 0.801 mm^-1, F（000） = 670, the final R = 0.0337 and wR = 0.0859 for 5122 observed reflections with I 〉 2σ（I）, And those for 2： monoclinic, space group P2/n, a = 7.1866（11）, b = 14.144（2）, c = 14.407（2）/k, β = 101.427（2）°, C32H28N4O6Zn, Mr = 629.95, V = 1435.4（4） A3, Z = 2, Dc = 1.457 g/cm3, μ（MoKa） = 0.908 mm^-1, F（000） = 652, the final R = 0.0438 and wR= 0.0821 for 2546 observed reflections with I〉 2σ（I）. In 1 and 2, ph or tp ligauds bridge the six-coordinated copper（Ⅱ） or four-coordinated zinc（Ⅱ） ions forming 1D zigzag chains while L ligands act as the terminal monodentate ligand. It is noted that weak non-classical C-H…O plays the important and dominating roles in the formation of 2D supramolecular architectures of 1, but in 2 non-classical C-H…O and aromatic π…π Stacking interactions are quite important and play dominant roles in the self-assembly of 2D supramolecular architectures.
基金financially supported by the Key Technologies R&D Program (No. 2014BAD23B01)National Natural Science Foundation of China (Nos. 21202025, 21372052)
文摘A series of novel 5-（trifluoromethyl）-1H-pyrazole-4-carboxamide derivatives（6a–6n, 7a, 7b, and 8a-8f）were synthesised by placing the amide bond at the 4-position of the pyrazole ring. These derivatives differed from the structure of chlorantraniliprole analogues with the amide bond at the 5-position of the pyrazole ring. Preliminary bioassay results revealed that a few title compounds exhibited good insecticidal activities against lepidopteran pests, such as Plutella xylostella, Mythimna separate, Heliothis armigera, and Ostrinia nubilalis. Some title compounds also elicited broad-spectrum insecticidal activities against dipterous insects including Culex pipiens pallens after altering the amide position. Similar to pyrazole-5-carboxamide analogues, compounds 6b and 6e showed 100% insecticidal activity against P. xylostella, C. pipiens pallens, and M. separate at concentrations of 200, 2, and 200 mg/m L, respectively.This finding suggested that 5-（trifluoromethyl）-1H-pyrazole-4-carboxamide derivatives are potential alternative insecticides for management of agriculture pests.
基金financial support from the National Natural Science Foundation of China(No.22208279)Financial support from the Fuzhou University(No.0041/511095)。
文摘A visible light-promoted fast photochemical Wolff rearrangement was developed toward synthesis ofα-substituted amides in continuous flow with the use of a photochemical oscillatory flow reactor(POFR).The control experiment indicates that a fast process of the Wolff rearrangement(<40 s)is involved.Notably,this protocol does not require excess use of any reactants,and the resultingα-substituted amides could be isolated by recrystallization in good to excellent yields.
基金The National Natural Science Foundation of China(No.22177136)CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.CIFMS-2021-I2M-1-007,2022-I2M-2-002)。
文摘Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development.The advantageous effects of covalent compounds compared with non-covalent ones are highly dependent on electrophilic warheads.Hence,electrophilic warheads with tunable reactivity and selectivity are highly demanded in fields of medicinal chemistry and chemical biology.Herein,we report a novel electrophilic warhead,chloromethyl group activated by thiol-substituted 1,2,4-triazole.Interestingly,a pair of regioisomers could be simultaneously occurred in the step of alkylation during the synthesis of this unique motif.This is a rare example that the alkylation could simultaneously generate these two separable regioisomers of 1,2,4-triazole at the nitrogen or sulfur atom.The covalent-working mechanism of this new warhead is confirmed by various chemoproteomics experiments including target identification and binding site mapping.Importantly,the reactivity and selectivity of this new electrophilic warhead could be efficiently tuned by virtue of stereo effect.Interestingly,one pair of regioisomers(19S and 19X)induced distinct modes of cell death.Isomer 19S could induce apoptosis of colon cancer cells while 19X could induce both apoptosis and ferroptosis.Together,this study provides pairs of novel electrophilic warheads that could be useful not only in supporting the design of covalent compounds for drug discovery but also in providing chemical probes for the fundamental biological study.
基金supported by the Chinese Academy of Sciences CAS Project for Young Scientists in Basic Research(No.YSBR-027)。
文摘Temperature plays a crucial role in regulating polymorphism in supramolecular polymers.Understanding the mechanism behind temperature-dependent supramolecular polymorphism is crucial as it provides an opportunity to tailor polymorphs for specific properties and applications.In this study,we present our findings on a naphthalimide-substituted benzene-1,3,5-tricarboxamide derivative,R-Nap-1,which exhibits two distinct polymerization pathways at varying temperatures.At 313 K,polymerization results in the formation of an M-chiral polymorph,whereas at 253 K,a P-chiral polymorph is formed.Both polymorphs are notably stable,remaining unchanged for over six months under ambient conditions.Theoretical calculations and experimental investigations allowed us to elucidate the mechanisms underlying these polymorphic transformations.The formation of the M-chiral polymorph at 313 K is attributed to the nucleation and growth of R-Nap-1 monomers once their concentration surpasses a critical threshold.Conversely,at lower temperatures(e.g.,253 K),the monomers undergo facile transformation into dimers due to a lower energy barrier and reduced Gibbs energy compared to the monomeric state.Subsequently,these dimers undergo nucleation-elongation to form the P-chiral polymorph when their concentration exceeds the critical polymerization concentration.The stability and lack of interconversion between the two polymorphs can be attributed to their close thermodynamic stabilities,as evidenced by variable-temperature CD spectra and DFT calculations.These findings highlight the importance of accurate temperature control in supramolecular polymerization processes,making a significant contribution to the understanding of supramolecular polymorphism,thus advancing the field of supramolecular chemistry.
