Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide.The metabolism of ethanol generates reactive oxygen species,which play a significant role in the deterio-ration of alcoholic l...Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide.The metabolism of ethanol generates reactive oxygen species,which play a significant role in the deterio-ration of alcoholic liver disease(ALD).Antioxidant phytochemicals,such as polyphenols,regulate the expression of ALD-associated proteins and peptides,namely,catalase,superoxide dismutase,glutathione,glutathione peroxidase,and glutathione reductase.These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1--NF--E2--related factor--2 pathway and antioxidant responsive elements.Furthermore,these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines.These phenomena are likely induced via the regulation of mitogen--activating protein kinase(MAPK)pathways by plant antioxidants,similar to preconditioning in ischemia-reperfusion models.Although the relationship between plant antioxidants and ALD has not been adequately investigated,plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.展开更多
Haloacetamides（HAMs） are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residue...Haloacetamides（HAMs） are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S_N2 reaction mechanism.Toxicity of the monohalogenated HAMs（iodoacetamide, IAM; bromoacetamide, BAM;or chloroacetamide, CAM） varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints.Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM 〉 BAM 〉 CAM for Rad51, and BAM ≈ IAM 〉 CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM.展开更多
Pyridinium ylids 4 were generated as reaction intermediates from the decarboxylation of pyridinium betaines 3, which were prepared from the reactions of a-amino acid ester hydrochlorides with 2, 4, 6-triphenylpyrylium...Pyridinium ylids 4 were generated as reaction intermediates from the decarboxylation of pyridinium betaines 3, which were prepared from the reactions of a-amino acid ester hydrochlorides with 2, 4, 6-triphenylpyrylium tetrafluoroborate. Protonation, addition and substitution reactions of 4 with electrophiles were studied in this paper.展开更多
A novel trifunctional initiator with one alkyne and two trifluoromethanesulfonate moieties was synthesized from a protected alcohol 5-hydroxyl-2-phenyl-1, 3-dioxane. The alkyne func- tionalized intermediate with two p...A novel trifunctional initiator with one alkyne and two trifluoromethanesulfonate moieties was synthesized from a protected alcohol 5-hydroxyl-2-phenyl-1, 3-dioxane. The alkyne func- tionalized intermediate with two protected alcohol groups was synthesized by reacting with propargyl bromide. The alcohol groups were cleaved using a mixture of tetrahydrofuran and hydrochloric acid aqueous solution. In the last step the initiator was synthesized us- ing triflic anhydride in carbon tetrachloride. The initiator was characterized by 1H NMR and used for the polymerization of 2-ethyl-2-oxazoline which gives polymers with narrow distribution. For comparison a similar initiator with two tosylates was prepared and used for the polymerization of the monomer 2-ethyl-2-oxazoline, the resulting product has a wide molecular weight distribution and most of the initiator remains unreacted after 24 h which may be due to the steric hindrance between the two tosylate groups. To further explore the steric hindrance phenomenon, a linear tosylate initiator was synthesized, but still some of the initiator remains unreacted, illustrating that both steric hindrance and electrophilic balance affect the efficiency of the cationic ring-opening polymerization. All of the polymers were characterized in detail by using IH NMR, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy, and size exclusion chromatography to confirm the purity and distribution of the polymers.展开更多
Transition-metal-catalyzed cross-electrophile coupling has emerged as a reliable method for constructing carbon–carbon bonds.Herein,we report a general method,cobalt-catalyzed reductive alkynylation,to construct C(sp...Transition-metal-catalyzed cross-electrophile coupling has emerged as a reliable method for constructing carbon–carbon bonds.Herein,we report a general method,cobalt-catalyzed reductive alkynylation,to construct C(sp)-C(sp^(3))and C(sp)-C(sp^(2))bonds.This presented reaction has a broad substrate scope,enabling the efficient cross-electrophile coupling between alkynyl bromides with alkyl halides and aryl or alkenyl(pseudo)halides.This presented reaction is conducted under mild conditions,tolerating many functional groups,thus suitable for the modification and synthesis of biologically active molecules.展开更多
Reported herein is the design of a new catalytic paradigm by synergistically combining sequential paired electrosynthesis with halogen-bonding(XB)activation for the cyclization of organochlorides with olefins.This dua...Reported herein is the design of a new catalytic paradigm by synergistically combining sequential paired electrosynthesis with halogen-bonding(XB)activation for the cyclization of organochlorides with olefins.This dual activation strategy enables rapid access to densely functionalized 2-alkylidene-tetrahydrofurans with exclusive Z-selectivities,which are challenging to be synthesized by other methods.4,4′-Di-tert-butyl-2,2′-bipyridine(dtbbpy)showed an unprecedented reactivity as a XB acceptor to activate C-Cl bond by shifting its reduction potential positively by 220 m V.Distinctly different from previous electroreductions of C-Cl bonds relying upon high electrode potentials or matched redox properties between mediators and organochlorides,the XB activator employed herein has no limit on the abovementioned redox property matching but can lower the applied electrode potentials.The decreased operating potential allows broad functional group tolerance,which was highlighted by the late-stage functionalization of 11 examples of drugs and natural products-derived alkenes.展开更多
Cross-electrophile coupling of triazine esters with aryl bromides could be facilely accomplished by employing nickel as catalyst,magnesium as metal mediator,and lithium chloride as additive.The reactions proceeded eff...Cross-electrophile coupling of triazine esters with aryl bromides could be facilely accomplished by employing nickel as catalyst,magnesium as metal mediator,and lithium chloride as additive.The reactions proceeded efficiently in THF at room temperature through C—O bond activation to afford an array of structurally different diaryl ketones in moderate to good yields with wide functional group tolerance.Control experiments showed that nickel,magnesium,lithium chloride,and THF are all indispensable for the good performance of the coupling reaction.Preliminary mechanistic exploration indicated that in situ formed arylmagnesium reagent by the insertion of magnesium into aryl bromide might serve as the key intermediate of the cross-coupling.The method which avoids the utilization of moisture-labile and relatively difficult-to-obtain organometallics is step-economical,cost-efficient,and operationally simple,potentially serving as an attractive alternative to documented methods.展开更多
An example of iron-catalyzed cross-electrophile couplingof inert C-O bonds with alkyl bromides via aniron/B_(2)pin_(2) catalytic system has been developed.Aryl and heteroaryl carbamates can smoothly undergothis transf...An example of iron-catalyzed cross-electrophile couplingof inert C-O bonds with alkyl bromides via aniron/B_(2)pin_(2) catalytic system has been developed.Aryl and heteroaryl carbamates can smoothly undergothis transformation under mild conditions, deliveringthe alkylated products with good efficiency.This protocol exhibits good functional group compatibilityand enables the late-stage functionalizationof biorelevant compounds, thus providingexcellent opportunities for applications in medicinalchemistry. Control experiments and computationalstudies reveal that a high spin Fe(I/II/III) catalyticmechanism might be involved in this reactionthrough single electron transfer to activate alkylbromides, oxidative addition of aryl carbamates, andreductive elimination to form Csp^(2)-Csp^(3) bonds.展开更多
A new protocol for the NiC12-catalyzed cross-electrophile coupling of aryl bromides with pyrimidin-2-yl tosyl- ates to give the corresponding C2-arylation pyrimidine derivatives has been developed. This study provides...A new protocol for the NiC12-catalyzed cross-electrophile coupling of aryl bromides with pyrimidin-2-yl tosyl- ates to give the corresponding C2-arylation pyrimidine derivatives has been developed. This study provides an improvement over previous methods by using pyrimidin-2-yl tosylates instead of halides as coupling partners that are stable and easily available.展开更多
Asymmetric synthesis of enantioenriched azo compounds bearing tetrasubstituted stereocenter was achieved through chiral N,N′-dioxide/metal Lewis acid promoted interrupted Japp-Klingemann reaction of aryldiazonium tet...Asymmetric synthesis of enantioenriched azo compounds bearing tetrasubstituted stereocenter was achieved through chiral N,N′-dioxide/metal Lewis acid promoted interrupted Japp-Klingemann reaction of aryldiazonium tetrafluoroborate salts with nucleophiles under mild conditions. This protocol features wide substrate scope and good functional group compatibility.Azaarene-containing chiral azo compounds were stable enough in Japp-Klingemann reaction condition. The key to success of the reaction was the employment of metal salt/N,N′-dioxide ligand and the dual-task roles of the base. Moreover, the X-ray crystal structure of Ni(II)/N,N′-dioxide/substrate complex confirmed that the substrate was activated by bidentate coordination, which shed light on the origin of chiral control of the reaction.展开更多
We report a Ni-catalyzed three-component cross-electrophile coupling of alkynes with alkenyl halides and fluoroalkyl halides to generate fluoroalkyl-incorporated 1,3-dienes.This mild and operationally simple protocol ...We report a Ni-catalyzed three-component cross-electrophile coupling of alkynes with alkenyl halides and fluoroalkyl halides to generate fluoroalkyl-incorporated 1,3-dienes.This mild and operationally simple protocol is distinguished by its broad substrate scope and excellent chemo-,regio-,and stereo-selectivity,offering a new and organometallic agent-free platform for the construction of fluoroalkyl-incorporated diene motifs.Preliminary mechanistic studies have been conducted to probe the potential reaction pathway.展开更多
In this paper,we developed an electrophilic ring-opening reaction,which is beyond the strained small ring system.Under reductive nickel catalysis,ring-opening of diverse benzofurans via endocyclic inert carbon–oxygen...In this paper,we developed an electrophilic ring-opening reaction,which is beyond the strained small ring system.Under reductive nickel catalysis,ring-opening of diverse benzofurans via endocyclic inert carbon–oxygen bond cleavage can be achieved with an array of inactivated secondary and tertiary alkyl halides as coupling partners,allowing for the preparation of a series of(E)-o-alkenylphenols with excellent E/Z-selectivity and high functional tolerance.The utility of this method was further demonstrated through derivatizations of the ring-opening products using the o-hydroxyl group as a functional handle,providing various organic compounds in good to high efficiency.展开更多
基金Supported by JSPS KAKENHI Grant Number 25450196grants-in-aid from The Ministry of Agriculture,Forestry and Fisheries of Japan
文摘Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide.The metabolism of ethanol generates reactive oxygen species,which play a significant role in the deterio-ration of alcoholic liver disease(ALD).Antioxidant phytochemicals,such as polyphenols,regulate the expression of ALD-associated proteins and peptides,namely,catalase,superoxide dismutase,glutathione,glutathione peroxidase,and glutathione reductase.These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1--NF--E2--related factor--2 pathway and antioxidant responsive elements.Furthermore,these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines.These phenomena are likely induced via the regulation of mitogen--activating protein kinase(MAPK)pathways by plant antioxidants,similar to preconditioning in ischemia-reperfusion models.Although the relationship between plant antioxidants and ALD has not been adequately investigated,plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.
基金partial support from the U.S.Army Engineer Research and Development Center and the Army Environmental Quality Technology program, CESU W9132T-16-2-0005 (MJP)partly supported by the interagency agreement IAG #NTR 12003 from the National Institute of Environmental Health Sciences/Division of the National Toxicology Program to the National Center for Advancing Translational Sciences, National Institutes of Health
文摘Haloacetamides（HAMs） are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S_N2 reaction mechanism.Toxicity of the monohalogenated HAMs（iodoacetamide, IAM; bromoacetamide, BAM;or chloroacetamide, CAM） varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints.Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM 〉 BAM 〉 CAM for Rad51, and BAM ≈ IAM 〉 CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM.
基金We want to express our sincere appreciation to Professor Joe Wilson of University of Kentucky and Professor Xiulin Ye of Peking University for their favorable suggestions and assistance for the work.
文摘Pyridinium ylids 4 were generated as reaction intermediates from the decarboxylation of pyridinium betaines 3, which were prepared from the reactions of a-amino acid ester hydrochlorides with 2, 4, 6-triphenylpyrylium tetrafluoroborate. Protonation, addition and substitution reactions of 4 with electrophiles were studied in this paper.
基金supported by the National Natural Scientific Foundation of China(No.21674107)the Fundamental Research Funds for the Central Universities(No.WK2340000066)the financial support from CASTWAS President’s PhD Fellowship Programme 2013
文摘A novel trifunctional initiator with one alkyne and two trifluoromethanesulfonate moieties was synthesized from a protected alcohol 5-hydroxyl-2-phenyl-1, 3-dioxane. The alkyne func- tionalized intermediate with two protected alcohol groups was synthesized by reacting with propargyl bromide. The alcohol groups were cleaved using a mixture of tetrahydrofuran and hydrochloric acid aqueous solution. In the last step the initiator was synthesized us- ing triflic anhydride in carbon tetrachloride. The initiator was characterized by 1H NMR and used for the polymerization of 2-ethyl-2-oxazoline which gives polymers with narrow distribution. For comparison a similar initiator with two tosylates was prepared and used for the polymerization of the monomer 2-ethyl-2-oxazoline, the resulting product has a wide molecular weight distribution and most of the initiator remains unreacted after 24 h which may be due to the steric hindrance between the two tosylate groups. To further explore the steric hindrance phenomenon, a linear tosylate initiator was synthesized, but still some of the initiator remains unreacted, illustrating that both steric hindrance and electrophilic balance affect the efficiency of the cationic ring-opening polymerization. All of the polymers were characterized in detail by using IH NMR, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy, and size exclusion chromatography to confirm the purity and distribution of the polymers.
基金the National Natural Science Foundation of China(Nos.22371273,22293011 and T2341001)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2023476)the National Science Foundation of Anhui Province(No.2208085J26)。
文摘Transition-metal-catalyzed cross-electrophile coupling has emerged as a reliable method for constructing carbon–carbon bonds.Herein,we report a general method,cobalt-catalyzed reductive alkynylation,to construct C(sp)-C(sp^(3))and C(sp)-C(sp^(2))bonds.This presented reaction has a broad substrate scope,enabling the efficient cross-electrophile coupling between alkynyl bromides with alkyl halides and aryl or alkenyl(pseudo)halides.This presented reaction is conducted under mild conditions,tolerating many functional groups,thus suitable for the modification and synthesis of biologically active molecules.
基金supported by the National Natural Science Foundation of China(21871019,22171015)Beijing Municipal Education Committee Project(KZ202110005003,KM202110005006)Beijing Natural Science Foundation(2222003)。
文摘Reported herein is the design of a new catalytic paradigm by synergistically combining sequential paired electrosynthesis with halogen-bonding(XB)activation for the cyclization of organochlorides with olefins.This dual activation strategy enables rapid access to densely functionalized 2-alkylidene-tetrahydrofurans with exclusive Z-selectivities,which are challenging to be synthesized by other methods.4,4′-Di-tert-butyl-2,2′-bipyridine(dtbbpy)showed an unprecedented reactivity as a XB acceptor to activate C-Cl bond by shifting its reduction potential positively by 220 m V.Distinctly different from previous electroreductions of C-Cl bonds relying upon high electrode potentials or matched redox properties between mediators and organochlorides,the XB activator employed herein has no limit on the abovementioned redox property matching but can lower the applied electrode potentials.The decreased operating potential allows broad functional group tolerance,which was highlighted by the late-stage functionalization of 11 examples of drugs and natural products-derived alkenes.
基金the financial support from Nanjing Tech University(Start-up Grant Nos.39837118 and 39837146)National Natural Science Foundation of China(22271062,22001121,and 22171137)+1 种基金Natural Science Foundation of Jiangsu Province(BK20180690)X.-Q.Chu is grateful for the financial support from the program of China Scholarship Council(No.201908320190).
文摘Cross-electrophile coupling of triazine esters with aryl bromides could be facilely accomplished by employing nickel as catalyst,magnesium as metal mediator,and lithium chloride as additive.The reactions proceeded efficiently in THF at room temperature through C—O bond activation to afford an array of structurally different diaryl ketones in moderate to good yields with wide functional group tolerance.Control experiments showed that nickel,magnesium,lithium chloride,and THF are all indispensable for the good performance of the coupling reaction.Preliminary mechanistic exploration indicated that in situ formed arylmagnesium reagent by the insertion of magnesium into aryl bromide might serve as the key intermediate of the cross-coupling.The method which avoids the utilization of moisture-labile and relatively difficult-to-obtain organometallics is step-economical,cost-efficient,and operationally simple,potentially serving as an attractive alternative to documented methods.
基金We thank the National Key Research and Development Program of China(grant no.2021YFA1500100)National Natural Science Foundation of China(grant nos.92156017 and 21890722)+3 种基金Natural Science Foundation of Sichuan(grant no.2021YJ0413)the Natural Science Foundation of Tianjin Municipality(grant no.19JCJQJC62300)Chongqing Postdoctoral Science Foundation(grant no.cstc2020jcyj-bshX0052)Affiliated Hospital of North Sichuan Medical College(grant no.2022JB001)for financial support.
文摘An example of iron-catalyzed cross-electrophile couplingof inert C-O bonds with alkyl bromides via aniron/B_(2)pin_(2) catalytic system has been developed.Aryl and heteroaryl carbamates can smoothly undergothis transformation under mild conditions, deliveringthe alkylated products with good efficiency.This protocol exhibits good functional group compatibilityand enables the late-stage functionalizationof biorelevant compounds, thus providingexcellent opportunities for applications in medicinalchemistry. Control experiments and computationalstudies reveal that a high spin Fe(I/II/III) catalyticmechanism might be involved in this reactionthrough single electron transfer to activate alkylbromides, oxidative addition of aryl carbamates, andreductive elimination to form Csp^(2)-Csp^(3) bonds.
基金We are thankful for the financial support from the National Natural Science Foundation of China （Nos. 21362032, 21362031 and 21562036） and Northwest Normal University （No. NWNU-LKQN- 15-1 ）.
文摘A new protocol for the NiC12-catalyzed cross-electrophile coupling of aryl bromides with pyrimidin-2-yl tosyl- ates to give the corresponding C2-arylation pyrimidine derivatives has been developed. This study provides an improvement over previous methods by using pyrimidin-2-yl tosylates instead of halides as coupling partners that are stable and easily available.
基金supported by the National Natural Science Foundation of China(21890723,21921002)。
文摘Asymmetric synthesis of enantioenriched azo compounds bearing tetrasubstituted stereocenter was achieved through chiral N,N′-dioxide/metal Lewis acid promoted interrupted Japp-Klingemann reaction of aryldiazonium tetrafluoroborate salts with nucleophiles under mild conditions. This protocol features wide substrate scope and good functional group compatibility.Azaarene-containing chiral azo compounds were stable enough in Japp-Klingemann reaction condition. The key to success of the reaction was the employment of metal salt/N,N′-dioxide ligand and the dual-task roles of the base. Moreover, the X-ray crystal structure of Ni(II)/N,N′-dioxide/substrate complex confirmed that the substrate was activated by bidentate coordination, which shed light on the origin of chiral control of the reaction.
基金financial support provided by the National Natural Science Foundation of China(Nos.21991123,21971036,21901036)the Shanghai Rising-Star Program(No.20QA1400200)。
文摘We report a Ni-catalyzed three-component cross-electrophile coupling of alkynes with alkenyl halides and fluoroalkyl halides to generate fluoroalkyl-incorporated 1,3-dienes.This mild and operationally simple protocol is distinguished by its broad substrate scope and excellent chemo-,regio-,and stereo-selectivity,offering a new and organometallic agent-free platform for the construction of fluoroalkyl-incorporated diene motifs.Preliminary mechanistic studies have been conducted to probe the potential reaction pathway.
基金supported by National Natural Science Foundation of China(grant no.21772183)the Fundamental Research Funds for the Central Universities(grant no.WK2060190086)“1000-Youth Talents Plan”start-up funding as well as the University of Science and Technology of China.
文摘In this paper,we developed an electrophilic ring-opening reaction,which is beyond the strained small ring system.Under reductive nickel catalysis,ring-opening of diverse benzofurans via endocyclic inert carbon–oxygen bond cleavage can be achieved with an array of inactivated secondary and tertiary alkyl halides as coupling partners,allowing for the preparation of a series of(E)-o-alkenylphenols with excellent E/Z-selectivity and high functional tolerance.The utility of this method was further demonstrated through derivatizations of the ring-opening products using the o-hydroxyl group as a functional handle,providing various organic compounds in good to high efficiency.
