P450 enzymes-catalyzed aromatic hydroxylation plays an important role in detoxification,biosynthesis,and potential carcinogenic effect of aromatic compounds.Though it has been explored for decades,the actual process o...P450 enzymes-catalyzed aromatic hydroxylation plays an important role in detoxification,biosynthesis,and potential carcinogenic effect of aromatic compounds.Though it has been explored for decades,the actual process of aromatic hydroxylation and mechanism of regioselectivity catalyzed by cytochrome P450 monooxygenases remained ambiguous.Here,we have resolved these issues.With a stable chiral organofluorine probe,and especially with X-ray data of two isolated arene oxides derivatives,we demonstrate that an arene oxide pathway is definitely involved in P450-catalyzed aromatic hydroxylation.By the capture,isolation,identification and reactivity exploration of the arene 1,2-oxide and arene 2,3-oxide intermediates,together with advanced QM calculations,the mechanism of how two intermediates go to the same product has been elucidated.In addition to the model substrate,we also confirmed that an arene oxide intermediate is involved in the P450-catalyzed hydroxylation pathway of a natural product derivative methyl cinnamate,which indicates that this intermediate appears to be universal in P450-catalyzed aromatic hydroxylation.Our work not only provides the most direct evidence for the arene oxide pathway and new insights into the regioselectivity involved in P450-catalyzed aromatic hydroxylation,but also supplies a new synthetic approach to achieve the dearomatization of aromatic compounds.展开更多
UiO-66-H MOFs can effectively catalyze the direct selective oxidation of methane(DSOM)to high value-added oxygenates under mild conditions.However,UiO-66-NH_(2)with benzene-1,4-dicarboxylate(NH_(2)-BDC)ligand modifyin...UiO-66-H MOFs can effectively catalyze the direct selective oxidation of methane(DSOM)to high value-added oxygenates under mild conditions.However,UiO-66-NH_(2)with benzene-1,4-dicarboxylate(NH_(2)-BDC)ligand modifying the Zr-oxo nodes exhibits relatively inferior catalytic performance for DSOM.Here,a combination of density functional theory(DFT)calculations and experiments was employed to explore the underlying reasons for the limited catalytic activity of UiO-66-NH_(2).The results indicate that the methane hydroxylation performance of UiO-66-NH_(2)is almost unaffected by the increase of·OH concentration.This is attributed to the formation of substantial non-covalent hydrogen bonds between the oxygen atoms of oxygenic species on the Zr-oxo nodes and the hydrogen atoms of-NH_(2)groups,which diminishes the spin density distribution on the active sites of(·OH)m/UiO-66-NH_(2),leading to minimal change of the adsorption energy of CH_(4).Additionally,the calculated adsorption energies(Eads)of CH_(4)exhibit a linear relationship with the catalytic activity of UiO-66-NH_(2)for DSOM reaction.展开更多
A catalytic diastereoselective Prins reaction for hydroxymethylation and hydroxylation of 1,3-diarylpropene was successfully utilized to prepare various 1,3-dioxanes7 in 14-88%yields.Take advantage of the synthetic in...A catalytic diastereoselective Prins reaction for hydroxymethylation and hydroxylation of 1,3-diarylpropene was successfully utilized to prepare various 1,3-dioxanes7 in 14-88%yields.Take advantage of the synthetic intermediate7h,the key B/C rings in brazilin core could be constructed by the sequential of Friedel-Crafts/Ullmann-Ma rather than Ullmann-Ma/Friedel-Crafts reactions.展开更多
Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts.Here a green and efficient asymmetric hydroxylation of primary and secondary C-H bon...Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts.Here a green and efficient asymmetric hydroxylation of primary and secondary C-H bonds at propargylic positions has been established.A series of optically active propargylic alcohols were prepared with high regio-and enantioselectivity(up to 99%ee)under mild reaction conditions by using P450tol,while the C≡C bonds in the molecule remained unreacted.This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols.In addition,we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96%ee,which’s an important synthetic intermediate of antifungal drug Ravuconazole.展开更多
S─mephenytoin and debrisoquin hydroxylation abilities were investigated in 118 normal Chinese Zhuang minority volunteers after co─administration po 100 mg racemic mephenytoin(MP)and 10 mg debrisoquin (DB). The rat...S─mephenytoin and debrisoquin hydroxylation abilities were investigated in 118 normal Chinese Zhuang minority volunteers after co─administration po 100 mg racemic mephenytoin(MP)and 10 mg debrisoquin (DB). The ratio between S─and R─enantiomers of mephenytoin in urinewas determined by implication of GC─NPD and used as the measure of the drug hydroxylation. 2 ofthe 118 subjects had S/R ratios greater than 1.0 and were poor hydroxylators of S─mephenytoin. The frequency of S─mephenytoin poor metabolizers (PM) was 10.2%. No PM of debrisoquin was found in the volunteers. It indicated that there was no relationship between S─mephenytoin P(4′)─ hydroxylation and debrisoquin 4─hydroxylation polymorphisms in Chinese Zhuang Minority population. In addition, 16 of the 118 volunteers(4 PMs and 12 EMs of S-mephenytoin) were se─lected to conduct the elimination kinetic studies of racemic mephenytoin and debrisoquin in urine. The pharmacokinetic parameters of S─, R─mephenytoin, DB and 4─OH─DB were calculated.展开更多
Keggin type molybdovanadophosphoric heteropoly acids, H3＋nPMo12-nVnO40（n=1-3）, were prepared by a novel environmentally benign method, and their catalytic performances were evaluated via hydroxylation of benzene to...Keggin type molybdovanadophosphoric heteropoly acids, H3＋nPMo12-nVnO40（n=1-3）, were prepared by a novel environmentally benign method, and their catalytic performances were evaluated via hydroxylation of benzene to phenol with hydrogen peroxide as oxidant in a mixed solvent of glacial acetic acid and acetonitrile. Various reaction parameters, such as reaction time, reaction temperature, ratio of benzene to hydrogen peroxide, concentration of aqueous hydrogen peroxide, ratio of glacial acetic acid to acetonitrile in solvent and catalyst con- centration, were changed to obtain an optimal reaction conditions. H3＋nPMo12-nVnO40（n=1-3） are revealed to be highly efficient catalyst for hydroxylation of benzene. In case of H5PMo10V2O40, a conversion of benzene of 34.5% with the selectivity of phenol of 100% can be obtained at the optimal reaction conditions.展开更多
Fe-containing graphitic carbon nitride（Fe-g-C3N4） materials were synthesized via one-step pyroly-sis of FeCl3 and dicyandiamide. The physicochemical properties of the synthesized Fe-g-C3N4 sam-ples were characterize...Fe-containing graphitic carbon nitride（Fe-g-C3N4） materials were synthesized via one-step pyroly-sis of FeCl3 and dicyandiamide. The physicochemical properties of the synthesized Fe-g-C3N4 sam-ples were characterized by N2 adsorption-desorption, X-ray diffraction, thermal gravimetric, Fourier transform infrared, UV-vis diffuse reflectance, X-ray photoelectron spectroscopy, and transmission electron microscopy. The Fe cations were anchored by nitrogen-rich g-C3N4, whereas the graphitic structures of g-C3N4 were retained after the introduction of Fe. As heterogeneous catalysts, Fe-g-C3 N4 exhibited good catalytic activity in the direct hydroxylation of benzene to phenol with H2O2, affording a maximum yield of phenol of up to 17.5%. Compared with other Fe- and V-containing g-C3N4 materials, Fe-g-C3N4 features a more convenient preparation procedure and higher catalytic productivity of phenol.展开更多
Self‐assembled mesoporous polyoxometalate‐based ionic hybrid catalyst,[PxyDim]2.5PMoV2,was prepared by combining p‐xylene‐tethered diimidazole ionic liquid[PxyDim]Cl2with Keggin‐structured V‐substituted polyoxom...Self‐assembled mesoporous polyoxometalate‐based ionic hybrid catalyst,[PxyDim]2.5PMoV2,was prepared by combining p‐xylene‐tethered diimidazole ionic liquid[PxyDim]Cl2with Keggin‐structured V‐substituted polyoxometalate H5PMo10V2O40.The obtained hybrid was shown to be a mesostructured and hydrophobic material with good thermal stability.In the H2O2‐based hydroxylation of benzene to phenol,the hybrid showed extraordinary catalytic activity and rate,and quite stable reusability.The unique hydrophobic properties and mesoporous structure of the hybrid were responsible for its excellent catalytic performance.展开更多
A new route towards phenol production by one-step selective hydroxylation of benzene with hydrogen peroxide over ultrafine titanium silicalites-1(TS-1) in a submerged ceramic membrane reactor was developed, which can ...A new route towards phenol production by one-step selective hydroxylation of benzene with hydrogen peroxide over ultrafine titanium silicalites-1(TS-1) in a submerged ceramic membrane reactor was developed, which can maintain the in situ removal of ultrafine catalyst particles from the reaction slurry and keep the process continuous.The effects of key operating parameters on the benzene conversion and phenol selectivity, as well as the membrane filtration resistance were examined by single factor experiments. A continuous reaction process was carried out under the obtained optimum operation conditions. Results showed that the system can be continuously and stably operated over 20 h, and the benzene conversion and phenol selectivity kept at about 4% and 91%, respectively. The ceramic membrane exhibits excellent thermal and chemical stability in the continuous reaction process.展开更多
This ranearch is focused on the, develonment of a simnle design model of the submerged catalysis/membrane filtration （catalysis/MF） system for phenol hydroxylation over TS-1 based on the material balance of the phen...This ranearch is focused on the, develonment of a simnle design model of the submerged catalysis/membrane filtration （catalysis/MF） system for phenol hydroxylation over TS-1 based on the material balance of the phenol under steady state and the reported kinetic studies. Based on the developed model, the theoretical phenol Conversions at steady state could be calculated using the kinetic parameters obtained from the previous batch experiments. The theoretical conversions are in good agreement with the experimental data obtained in the submerged catalysis/MF system within relative error of ±5%. The model can be used to determine the optimal experimental conditions to carry out the phenol hydroxylation over TS-1 in the submerged catalysis/MF system.展开更多
MCM-41 zeolite and Iron (Ⅱ) -Phen/MCM-41 zeolite have been preparedand characterized by XRD,IR, NH3-TPD, BET and UV-Vis. The Iron(Ⅱ)-Phen/MCM-41 zeolite+30% H2O2 system is capable for catalyzing hydroxylation of Phe...MCM-41 zeolite and Iron (Ⅱ) -Phen/MCM-41 zeolite have been preparedand characterized by XRD,IR, NH3-TPD, BET and UV-Vis. The Iron(Ⅱ)-Phen/MCM-41 zeolite+30% H2O2 system is capable for catalyzing hydroxylation of Phenol.展开更多
Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-p...Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.展开更多
The selective H2O2 oxidation reaction of phenol to catechol on Ln-ZrO2 catalyst has improved the selectivity to 85%, to compare with the conventional titania catalyst. With addition of rare earth such as lanthanum, ne...The selective H2O2 oxidation reaction of phenol to catechol on Ln-ZrO2 catalyst has improved the selectivity to 85%, to compare with the conventional titania catalyst. With addition of rare earth such as lanthanum, neodymium, to zirconia as catalyst, the selectivity is increased by 72% and 60% respectively in comparison with the bare titania catalyst.展开更多
A new Fenton-like system in a medium of hydrophilic triethylammonium type of ionic liquid（IL） was used for the hydroxylation of benzene to phenol. The triethylammonium acetate（[Et3NH][CH3COO]） IL exhibited retarda...A new Fenton-like system in a medium of hydrophilic triethylammonium type of ionic liquid（IL） was used for the hydroxylation of benzene to phenol. The triethylammonium acetate（[Et3NH][CH3COO]） IL exhibited retardation performance for the decomposition of H2O2 and protection performance for the further oxidation of phenol, thus the yield and selectivity to phenol were promoted greatly. The acidity of the system was proved to be an important factor for the selectivity to phenol. The utilization of H2O2 and the selectivity to phenol, as well as the Turnover number（TON） of the catalyst were effectively enhanced by a benzene-[Et3NH][CH3COO] bi-phase system. The catalyst with [Et3NH][CH3COO] IL was recycled with stable catalytic performance.展开更多
The hydroxylation reaction mechanism of nitrosodimethylamine（NDMA） by oxygen atom was theoretically investigated at the B3LYP/6-31G＊＊ level. It has been found that the path of the oxydation of the C―H bond is eas...The hydroxylation reaction mechanism of nitrosodimethylamine（NDMA） by oxygen atom was theoretically investigated at the B3LYP/6-31G＊＊ level. It has been found that the path of the oxydation of the C―H bond is easier than the path involving a Singlet/Triplet crossing. The study of the potential surface shows that both solvent effect at B3LYP/6-31G＊＊ level and different method at more credible MP2/6-311G＊＊ level in the gas phase have no effect on the hydroxylation reaction mechanism. The oxidation hydroxylation process of NDMA by O is exothermic reaction and easy to occur.展开更多
Liquid phase catalytic hydroxylation of phenol by Fe-containing metal-organic framework, Fe-BTC (BTC = 1,3,5-benzenetricarboxylate) using 30% H2O2 as an oxidant and H2O as solvent showed good activity and stability un...Liquid phase catalytic hydroxylation of phenol by Fe-containing metal-organic framework, Fe-BTC (BTC = 1,3,5-benzenetricarboxylate) using 30% H2O2 as an oxidant and H2O as solvent showed good activity and stability under mild reaction conditions. Phenol reacts with hydrogen peroxide over Fe-BTC to produce two main products, viz., catechol and hydroquinone. The effect of temperature, time, substrate/hydrogen peroxide mole ratio and amount of catalyst on catalytic performance were studied. The catalyst could be reused four times without losing significant loss of catalytic performance. The crystallinity and structure of catalyst were unchanged during the catalysis reaction, as confirmed by comparison of XRD and SEM of the fresh and reused catalyst. A reaction mechanism is proposed based on the experimental results.展开更多
Metallodeuteroporphyrins（MDPs） were employed as the catalysts for aerobic oxidation of β-pinene in absence of solvents and additives. Allylic hydroxylation products were found to be the main products from this prot...Metallodeuteroporphyrins（MDPs） were employed as the catalysts for aerobic oxidation of β-pinene in absence of solvents and additives. Allylic hydroxylation products were found to be the main products from this protocol. The catalytic activity of MDPs with different metal nuclei and the influences of technological conditions on this reaction were investigated. This catalytic system has bright application prospect since only eco-friendly and readily available dioxygen were needed.展开更多
Various catalysts, including the heteropolyacid(HPA) H4PMo11VO40, its cesium salts, and inorganic–organic dual modified HPA catalyst, were prepared and characterized by Fourier transform infrared spectroscopy(FT-IR),...Various catalysts, including the heteropolyacid(HPA) H4PMo11VO40, its cesium salts, and inorganic–organic dual modified HPA catalyst, were prepared and characterized by Fourier transform infrared spectroscopy(FT-IR), nuclear magnetic resonance(13C NMR), N2 adsorption, acid–base titration, electron spin resonance(ESR) and X-ray diffraction(XRD) techniques as well as elemental analysis. These prepared catalysts were used in the hydroxylation of benzene to phenol by H2O2 as oxidant. The inorganic–organic dual modified HPA Cs2.5(MIMPS)1.5PMo11VO40, prepared by partially exchanging Cs+with protons in H4PMo11VO40 and followed by the immobilization of 3-(1-methylimidazolium-3-yl)propane-1-sulfonate(MIMPS), led to a liquid–solid biphasic catalysis system in the hydroxylation, which showed the best catalytic performance in terms of reusability and catalytic activity. The high reusability of Cs2.5(MIMPS)1.5PMo11VO40 in the heterogeneous hydroxylation was probably due to its high resistance in leaching of bulk HPA into the reaction medium. The slightly enhanced catalytic activity for the catalyst was due to the acid sites available from MIMPS beneficial to the hydroxylation.展开更多
The regio- and stereo-selective hydroxylations of two ingenane diterpenoids, 20-deoxyingenol(1) and 13-oxyingenol dodecanoat(2), by the filamentous fungi Mortierella ramanniana and Gibberella fujikuroi were investigat...The regio- and stereo-selective hydroxylations of two ingenane diterpenoids, 20-deoxyingenol(1) and 13-oxyingenol dodecanoat(2), by the filamentous fungi Mortierella ramanniana and Gibberella fujikuroi were investigated in the present study. Four undescribed metabolites(3–6) of substrate 1 and two undescribed metabolites(7 and 8) of substrate 2 were isolated. All the lites were identified as hydroxylated ingenane derivatives by extensive NMR and HR-ESI-MS data analyses. All the biotransformed compounds and the substrates were evaluated for their cytotoxicities against three human cancer cell lines, including human colon cancer Caco-2, breast cancer MCF-7, and adriamycin(ADM)-resistant MCF-7/ADM cell lines. All ingenane alcohols(1, and 3–6) displayed no significant cytotoxic activities. The substrate 13-oxyingenol dodecanoat(2) showed moderate cytotoxicity with IC50 values being 35.59 ± 5.37 μmol·L^(-1)(Caco-2), 24.04 ± 4.70 μmol·L^(-1)(MCF-7), and 22.24 ± 5.19 μmol·L^(-1)(MCF-7/ADM). However, metabolites 7 and 8 displayed no significant cytotoxicity. These results indicated that the hydroxylation at the C^(-1)3 aliphatic acid ester of substrate 2 can significantly reduce the cytotoxic activity.展开更多
The direct hydroxylation of benzene to phenol catalyzed by activated carbon-supported Fe （Fe/AC） in acetonitrile using H2O2 as the oxidant was studied in a continuous flow reactor. Results showed that the continuous...The direct hydroxylation of benzene to phenol catalyzed by activated carbon-supported Fe （Fe/AC） in acetonitrile using H2O2 as the oxidant was studied in a continuous flow reactor. Results showed that the continuous operation could obtain high phenol yield of 28.1%, coupled with the turnover frequency of 3 h^-1, and high selectivity of 98% under mild condition. The catalyst was characterized by N2 adsorption/desorption, Boehm titration, X-ray photoelectron spectra, and Fourier transform infrared spectroscopy. It was observed that iron may interact with the carboxyl group forming iron-carboxylate like species, which act as the active phase. The apparent activation energy obtained by fitting an Arrhenius model to the experimental data was 13.4 kJ/mol. The reaction order was calculated to be about i, 0.2 for benzene and 0.7 for H202.展开更多
文摘P450 enzymes-catalyzed aromatic hydroxylation plays an important role in detoxification,biosynthesis,and potential carcinogenic effect of aromatic compounds.Though it has been explored for decades,the actual process of aromatic hydroxylation and mechanism of regioselectivity catalyzed by cytochrome P450 monooxygenases remained ambiguous.Here,we have resolved these issues.With a stable chiral organofluorine probe,and especially with X-ray data of two isolated arene oxides derivatives,we demonstrate that an arene oxide pathway is definitely involved in P450-catalyzed aromatic hydroxylation.By the capture,isolation,identification and reactivity exploration of the arene 1,2-oxide and arene 2,3-oxide intermediates,together with advanced QM calculations,the mechanism of how two intermediates go to the same product has been elucidated.In addition to the model substrate,we also confirmed that an arene oxide intermediate is involved in the P450-catalyzed hydroxylation pathway of a natural product derivative methyl cinnamate,which indicates that this intermediate appears to be universal in P450-catalyzed aromatic hydroxylation.Our work not only provides the most direct evidence for the arene oxide pathway and new insights into the regioselectivity involved in P450-catalyzed aromatic hydroxylation,but also supplies a new synthetic approach to achieve the dearomatization of aromatic compounds.
基金the financial support from National Natural Science Foundation of China(22363001,22378379,22479032,22022814)the National Key R&D Project(2022YFA1503900)+6 种基金the Natural Science Special Foundation of Guizhou University(No.202140)National Natural Science Foundation of China for Single-Atom Catalysis(22388102)the Youth Innovation Promotion Association CAS(Y2021057)Dalian Science Foundation for Distinguished Young Scholars(2021RJ10)Grant.YLU-DNL Fund(2022010)the Young Top-notch Talents of Liaoning Province(XLYC2203140)the Liaoning Foundation for Distinguished Young Scholars(2025JH6/101100011).
文摘UiO-66-H MOFs can effectively catalyze the direct selective oxidation of methane(DSOM)to high value-added oxygenates under mild conditions.However,UiO-66-NH_(2)with benzene-1,4-dicarboxylate(NH_(2)-BDC)ligand modifying the Zr-oxo nodes exhibits relatively inferior catalytic performance for DSOM.Here,a combination of density functional theory(DFT)calculations and experiments was employed to explore the underlying reasons for the limited catalytic activity of UiO-66-NH_(2).The results indicate that the methane hydroxylation performance of UiO-66-NH_(2)is almost unaffected by the increase of·OH concentration.This is attributed to the formation of substantial non-covalent hydrogen bonds between the oxygen atoms of oxygenic species on the Zr-oxo nodes and the hydrogen atoms of-NH_(2)groups,which diminishes the spin density distribution on the active sites of(·OH)m/UiO-66-NH_(2),leading to minimal change of the adsorption energy of CH_(4).Additionally,the calculated adsorption energies(Eads)of CH_(4)exhibit a linear relationship with the catalytic activity of UiO-66-NH_(2)for DSOM reaction.
基金support from National Natural Science Foundation of China(82260683 and 22267024)Scientific and Technological Project of Yunnan Precious Metals Laboratory(YPML-2023050265 and YPML-2023050217)+3 种基金Yunnan Science and Technology Talent and Platform Program(202105AG070012)the Top Young Talent of Ten Thousand Talents Program of Yunnan Province(D.L.and L.-D.S.)the Start-up Fund of Yunnan University of Chinese Medicine(2019YZG03)the Bioactive Ethnopharmacol Molecules Chemical Conversion and Application Innovation Team of Department of Education of Yunnan Province(2022).
文摘A catalytic diastereoselective Prins reaction for hydroxymethylation and hydroxylation of 1,3-diarylpropene was successfully utilized to prepare various 1,3-dioxanes7 in 14-88%yields.Take advantage of the synthetic intermediate7h,the key B/C rings in brazilin core could be constructed by the sequential of Friedel-Crafts/Ullmann-Ma rather than Ullmann-Ma/Friedel-Crafts reactions.
基金financial support from the National Natural Science Foundation of China(No.32271537 and 22061049)the Science and Technology Department of Guizhou province(QKHJCZK2021-036 and QKHRCPTGCC-2023-003)+1 种基金the Science and Technology Department of Zunyi(ZSKRPT-2020-5,ZSKH-2018-3,ZSKRPT-2021-5)Zunyi Medical University(QKH-2018-5772-014).
文摘Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts.Here a green and efficient asymmetric hydroxylation of primary and secondary C-H bonds at propargylic positions has been established.A series of optically active propargylic alcohols were prepared with high regio-and enantioselectivity(up to 99%ee)under mild reaction conditions by using P450tol,while the C≡C bonds in the molecule remained unreacted.This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols.In addition,we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96%ee,which’s an important synthetic intermediate of antifungal drug Ravuconazole.
文摘S─mephenytoin and debrisoquin hydroxylation abilities were investigated in 118 normal Chinese Zhuang minority volunteers after co─administration po 100 mg racemic mephenytoin(MP)and 10 mg debrisoquin (DB). The ratio between S─and R─enantiomers of mephenytoin in urinewas determined by implication of GC─NPD and used as the measure of the drug hydroxylation. 2 ofthe 118 subjects had S/R ratios greater than 1.0 and were poor hydroxylators of S─mephenytoin. The frequency of S─mephenytoin poor metabolizers (PM) was 10.2%. No PM of debrisoquin was found in the volunteers. It indicated that there was no relationship between S─mephenytoin P(4′)─ hydroxylation and debrisoquin 4─hydroxylation polymorphisms in Chinese Zhuang Minority population. In addition, 16 of the 118 volunteers(4 PMs and 12 EMs of S-mephenytoin) were se─lected to conduct the elimination kinetic studies of racemic mephenytoin and debrisoquin in urine. The pharmacokinetic parameters of S─, R─mephenytoin, DB and 4─OH─DB were calculated.
基金Supported by the National Natural Science Foundation of China （Nos.20306011, 20476046） and the Ph.D. Program Foundation for Chinese Universities （No.20040291002）.
文摘Keggin type molybdovanadophosphoric heteropoly acids, H3＋nPMo12-nVnO40（n=1-3）, were prepared by a novel environmentally benign method, and their catalytic performances were evaluated via hydroxylation of benzene to phenol with hydrogen peroxide as oxidant in a mixed solvent of glacial acetic acid and acetonitrile. Various reaction parameters, such as reaction time, reaction temperature, ratio of benzene to hydrogen peroxide, concentration of aqueous hydrogen peroxide, ratio of glacial acetic acid to acetonitrile in solvent and catalyst con- centration, were changed to obtain an optimal reaction conditions. H3＋nPMo12-nVnO40（n=1-3） are revealed to be highly efficient catalyst for hydroxylation of benzene. In case of H5PMo10V2O40, a conversion of benzene of 34.5% with the selectivity of phenol of 100% can be obtained at the optimal reaction conditions.
基金supported by the National Natural Science Foundation of China (21673024)Advanced Catalysis and Green Manufacturing Collaborative Innovation Center (ACGM2016-06-28)+1 种基金Foundation of State Key Laboratory of High-efficiency Utilization of Coal and Green Chemical Engineering (2017-K28)the Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (PPZY2015B145)~~
文摘Fe-containing graphitic carbon nitride（Fe-g-C3N4） materials were synthesized via one-step pyroly-sis of FeCl3 and dicyandiamide. The physicochemical properties of the synthesized Fe-g-C3N4 sam-ples were characterized by N2 adsorption-desorption, X-ray diffraction, thermal gravimetric, Fourier transform infrared, UV-vis diffuse reflectance, X-ray photoelectron spectroscopy, and transmission electron microscopy. The Fe cations were anchored by nitrogen-rich g-C3N4, whereas the graphitic structures of g-C3N4 were retained after the introduction of Fe. As heterogeneous catalysts, Fe-g-C3 N4 exhibited good catalytic activity in the direct hydroxylation of benzene to phenol with H2O2, affording a maximum yield of phenol of up to 17.5%. Compared with other Fe- and V-containing g-C3N4 materials, Fe-g-C3N4 features a more convenient preparation procedure and higher catalytic productivity of phenol.
基金supported by the National Natural Science Foundation of China (21506118,21476132,51574160)Shandong Province Founda-tion for Outstanding Young Scientist (BS2014CL030)~~
文摘Self‐assembled mesoporous polyoxometalate‐based ionic hybrid catalyst,[PxyDim]2.5PMoV2,was prepared by combining p‐xylene‐tethered diimidazole ionic liquid[PxyDim]Cl2with Keggin‐structured V‐substituted polyoxometalate H5PMo10V2O40.The obtained hybrid was shown to be a mesostructured and hydrophobic material with good thermal stability.In the H2O2‐based hydroxylation of benzene to phenol,the hybrid showed extraordinary catalytic activity and rate,and quite stable reusability.The unique hydrophobic properties and mesoporous structure of the hybrid were responsible for its excellent catalytic performance.
基金Supported by the National High Technology Research and Development Program(2012AA03A606)the National Natural Science Foundation(21306081,21125629)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20130920)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)of China
文摘A new route towards phenol production by one-step selective hydroxylation of benzene with hydrogen peroxide over ultrafine titanium silicalites-1(TS-1) in a submerged ceramic membrane reactor was developed, which can maintain the in situ removal of ultrafine catalyst particles from the reaction slurry and keep the process continuous.The effects of key operating parameters on the benzene conversion and phenol selectivity, as well as the membrane filtration resistance were examined by single factor experiments. A continuous reaction process was carried out under the obtained optimum operation conditions. Results showed that the system can be continuously and stably operated over 20 h, and the benzene conversion and phenol selectivity kept at about 4% and 91%, respectively. The ceramic membrane exhibits excellent thermal and chemical stability in the continuous reaction process.
基金Supported by the National-Basic Research Program of China （2009CB623406）, the National High Technology Research and Development Program of China （2007AA06A402） and the National Natural Science Foundation of China （20636020）.
文摘This ranearch is focused on the, develonment of a simnle design model of the submerged catalysis/membrane filtration （catalysis/MF） system for phenol hydroxylation over TS-1 based on the material balance of the phenol under steady state and the reported kinetic studies. Based on the developed model, the theoretical phenol Conversions at steady state could be calculated using the kinetic parameters obtained from the previous batch experiments. The theoretical conversions are in good agreement with the experimental data obtained in the submerged catalysis/MF system within relative error of ±5%. The model can be used to determine the optimal experimental conditions to carry out the phenol hydroxylation over TS-1 in the submerged catalysis/MF system.
文摘MCM-41 zeolite and Iron (Ⅱ) -Phen/MCM-41 zeolite have been preparedand characterized by XRD,IR, NH3-TPD, BET and UV-Vis. The Iron(Ⅱ)-Phen/MCM-41 zeolite+30% H2O2 system is capable for catalyzing hydroxylation of Phenol.
基金supported by the National Key R&D Program of China(2019YFA0904900)the National Natural Science Foundation of China(21877112,21837002,21721004)。
文摘Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.
文摘The selective H2O2 oxidation reaction of phenol to catechol on Ln-ZrO2 catalyst has improved the selectivity to 85%, to compare with the conventional titania catalyst. With addition of rare earth such as lanthanum, neodymium, to zirconia as catalyst, the selectivity is increased by 72% and 60% respectively in comparison with the bare titania catalyst.
基金Supported by the National Natural Science Foundation of China(Nos.20502017, 20872102)
文摘A new Fenton-like system in a medium of hydrophilic triethylammonium type of ionic liquid（IL） was used for the hydroxylation of benzene to phenol. The triethylammonium acetate（[Et3NH][CH3COO]） IL exhibited retardation performance for the decomposition of H2O2 and protection performance for the further oxidation of phenol, thus the yield and selectivity to phenol were promoted greatly. The acidity of the system was proved to be an important factor for the selectivity to phenol. The utilization of H2O2 and the selectivity to phenol, as well as the Turnover number（TON） of the catalyst were effectively enhanced by a benzene-[Et3NH][CH3COO] bi-phase system. The catalyst with [Et3NH][CH3COO] IL was recycled with stable catalytic performance.
基金Supported by the Foundation of Shanghai Municipal Education Commission,China(No.09YZ390)
文摘The hydroxylation reaction mechanism of nitrosodimethylamine（NDMA） by oxygen atom was theoretically investigated at the B3LYP/6-31G＊＊ level. It has been found that the path of the oxydation of the C―H bond is easier than the path involving a Singlet/Triplet crossing. The study of the potential surface shows that both solvent effect at B3LYP/6-31G＊＊ level and different method at more credible MP2/6-311G＊＊ level in the gas phase have no effect on the hydroxylation reaction mechanism. The oxidation hydroxylation process of NDMA by O is exothermic reaction and easy to occur.
文摘Liquid phase catalytic hydroxylation of phenol by Fe-containing metal-organic framework, Fe-BTC (BTC = 1,3,5-benzenetricarboxylate) using 30% H2O2 as an oxidant and H2O as solvent showed good activity and stability under mild reaction conditions. Phenol reacts with hydrogen peroxide over Fe-BTC to produce two main products, viz., catechol and hydroquinone. The effect of temperature, time, substrate/hydrogen peroxide mole ratio and amount of catalyst on catalytic performance were studied. The catalyst could be reused four times without losing significant loss of catalytic performance. The crystallinity and structure of catalyst were unchanged during the catalysis reaction, as confirmed by comparison of XRD and SEM of the fresh and reused catalyst. A reaction mechanism is proposed based on the experimental results.
基金funded by the Fundamental Research Funds for Jiangsu Key Lab of Biomass Energy and Material(No.JSBEM-S-201605)the National Natural Science Foundation of China(No.31600466)the Fundamental Research Funds for the Central Non-profit Research Institution of CAF(No.CAFYBB2014QA022)
文摘Metallodeuteroporphyrins（MDPs） were employed as the catalysts for aerobic oxidation of β-pinene in absence of solvents and additives. Allylic hydroxylation products were found to be the main products from this protocol. The catalytic activity of MDPs with different metal nuclei and the influences of technological conditions on this reaction were investigated. This catalytic system has bright application prospect since only eco-friendly and readily available dioxygen were needed.
基金Supported by the National Natural Science Foundation of China(20806075,20971109,21036006)the Program for Changjiang Scholars and Innovative Research Team in Chinese Universities(IRT0980)
文摘Various catalysts, including the heteropolyacid(HPA) H4PMo11VO40, its cesium salts, and inorganic–organic dual modified HPA catalyst, were prepared and characterized by Fourier transform infrared spectroscopy(FT-IR), nuclear magnetic resonance(13C NMR), N2 adsorption, acid–base titration, electron spin resonance(ESR) and X-ray diffraction(XRD) techniques as well as elemental analysis. These prepared catalysts were used in the hydroxylation of benzene to phenol by H2O2 as oxidant. The inorganic–organic dual modified HPA Cs2.5(MIMPS)1.5PMo11VO40, prepared by partially exchanging Cs+with protons in H4PMo11VO40 and followed by the immobilization of 3-(1-methylimidazolium-3-yl)propane-1-sulfonate(MIMPS), led to a liquid–solid biphasic catalysis system in the hydroxylation, which showed the best catalytic performance in terms of reusability and catalytic activity. The high reusability of Cs2.5(MIMPS)1.5PMo11VO40 in the heterogeneous hydroxylation was probably due to its high resistance in leaching of bulk HPA into the reaction medium. The slightly enhanced catalytic activity for the catalyst was due to the acid sites available from MIMPS beneficial to the hydroxylation.
文摘The regio- and stereo-selective hydroxylations of two ingenane diterpenoids, 20-deoxyingenol(1) and 13-oxyingenol dodecanoat(2), by the filamentous fungi Mortierella ramanniana and Gibberella fujikuroi were investigated in the present study. Four undescribed metabolites(3–6) of substrate 1 and two undescribed metabolites(7 and 8) of substrate 2 were isolated. All the lites were identified as hydroxylated ingenane derivatives by extensive NMR and HR-ESI-MS data analyses. All the biotransformed compounds and the substrates were evaluated for their cytotoxicities against three human cancer cell lines, including human colon cancer Caco-2, breast cancer MCF-7, and adriamycin(ADM)-resistant MCF-7/ADM cell lines. All ingenane alcohols(1, and 3–6) displayed no significant cytotoxic activities. The substrate 13-oxyingenol dodecanoat(2) showed moderate cytotoxicity with IC50 values being 35.59 ± 5.37 μmol·L^(-1)(Caco-2), 24.04 ± 4.70 μmol·L^(-1)(MCF-7), and 22.24 ± 5.19 μmol·L^(-1)(MCF-7/ADM). However, metabolites 7 and 8 displayed no significant cytotoxicity. These results indicated that the hydroxylation at the C^(-1)3 aliphatic acid ester of substrate 2 can significantly reduce the cytotoxic activity.
文摘The direct hydroxylation of benzene to phenol catalyzed by activated carbon-supported Fe （Fe/AC） in acetonitrile using H2O2 as the oxidant was studied in a continuous flow reactor. Results showed that the continuous operation could obtain high phenol yield of 28.1%, coupled with the turnover frequency of 3 h^-1, and high selectivity of 98% under mild condition. The catalyst was characterized by N2 adsorption/desorption, Boehm titration, X-ray photoelectron spectra, and Fourier transform infrared spectroscopy. It was observed that iron may interact with the carboxyl group forming iron-carboxylate like species, which act as the active phase. The apparent activation energy obtained by fitting an Arrhenius model to the experimental data was 13.4 kJ/mol. The reaction order was calculated to be about i, 0.2 for benzene and 0.7 for H202.
