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1.
Bioconjug Chem ; 30(7): 1969-1978, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31251559

RESUMO

The ortho-hydroxy-protected aryl sulfate (OHPAS) linker is composed of a diaryl sulfate backbone equipped with a latent phenol moiety at the ortho position of one of the aryl units. The Ar-OH released when the ortho phenol undergoes intramolecular cyclization and displaces the second aryl unit can be viewed as a payload. We have shown in the preceding paper that the OHPAS linkers are highly stable chemically and in various plasmas, yet release payloads when exposed to suitable triggering conditions. As an extension of the OHPAS system, we employed a para-hydroxy benzyl (PHB) spacer for coupling to nonphenolic payloads; this tactic again provided a highly stable system capable of smooth release of appended payloads. The PHB modification works beautifully for tertiary amine and N-heterocycle payloads.


Assuntos
Aminas/química , Compostos de Benzil/química , Compostos Heterocíclicos/química , Fenol/química , Sulfatos/química , Álcoois/síntese química , Álcoois/química , Aminas/síntese química , Compostos de Benzil/síntese química , Ciclização , DNA/síntese química , DNA/química , Compostos Heterocíclicos/síntese química , Fenol/síntese química , RNA/síntese química , RNA/química , Sulfatos/síntese química
2.
Molecules ; 24(7)2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974778

RESUMO

In solid-phase organic synthesis, Wang resin is traditionally used for the immobilization of acids, alcohols, phenols, and amines. We report the use of Wang resin for the traceless synthesis of ketones via acid-labile enol ethers. We demonstrate the practicality of this synthetic strategy on the solid-phase synthesis of pyrrolidine-2,4-diones, which represent the core structure of several natural products, including tetramic acid. Base-triggered condensation of pyrrolidine-2,4-diones yielded 4-hydroxy-1,1',2',5-tetrahydro-2H,5'H-[3,3'-bipyrrole]-2,5'-diones.


Assuntos
Álcoois , Cetonas , Álcoois/síntese química , Álcoois/química , Aminas/química , Cetonas/síntese química , Cetonas/química
3.
Nat Chem ; 11(6): 571-577, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30988418

RESUMO

One of the core barriers to developing C-H activation reactions is the ability to distinguish between multiple C-H bonds that are nearly identical in terms of electronic properties and bond strengths. Through recognition of distance and molecular geometry, remote C(sp2)-H bonds have been selectively activated in the presence of proximate ones. Yet achieving such unconventional site selectivity with C(sp3)-H bonds remains a paramount challenge. Here we report a combination of a simple pyruvic acid-derived directing group and a 2-pyridone ligand that enables the preferential activation of the distal γ-C(sp3)-H bond over the proximate ß-C(sp3)-H bonds for a wide range of alcohol-derived substrates. A competition experiment between the five- and six-membered cyclopalladation step, as well as kinetic experiments, demonstrate the feasibility of using geometric strain to reverse the conventional site selectivity in C(sp3)-H activation.


Assuntos
Álcoois/química , Carbono/química , Técnicas de Química Sintética/métodos , Hidrogênio/química , Álcoois/síntese química , Derivados de Benzeno/síntese química , Ciclização , Estrutura Molecular , Compostos Organometálicos/síntese química , Paládio/química , Piridonas/química , Piruvatos/química
4.
Org Lett ; 21(7): 2204-2208, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30892050

RESUMO

Asymmetric reduction of hydroxynaphthoquinones to secondary metabolites, (3 S,4 R)-3,4,8- and (2 S,4 R)-2,4,8-trihydroxy-1-tetralone, a putative biosynthetic diketo intermediate and a probable natural analogue, (3 S,4 R)-7-acetyl-3,4,8-trihydroxy-6-methyl-3,4-dihydronaphthalene-1(2 H)-one, using NADPH-dependent tetrahydroxynaphthalene reductase (T4HNR) of Magnaporthe grisea is described. This work implies the involvement of T4HNR or related enzymes during the (bio)synthesis of other dihydroarenediols by reduction of the hydroxynaphthoquinone scaffold containing substrates.


Assuntos
Álcoois/síntese química , Proteínas Fúngicas/biossíntese , Magnaporthe/química , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/biossíntese , Proteínas Fúngicas/química , Estrutura Molecular , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química
5.
Artigo em Inglês | MEDLINE | ID: mdl-30853700

RESUMO

Biological homochirality, such as that of l-amino acids, has been a puzzle with regards to the chemical origin of life. Asymmetric autocatalysis is a reaction in which a chiral product acts as an asymmetric catalyst to produce more of itself in the same absolute configuration. 5-Pyrimidyl alkanol was found to act as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. Asymmetric autocatalysis of 2-alkynyl-5-pyrimidyl alkanol with an extremely low enantiomeric excess of ca. 0.00005% exhibited significant asymmetric amplification to afford the same pyrimidyl alkanol with >99.5% enantiomeric excess and with an increase in the quantity of the same compound. We have employed asymmetric autocatalysis to examine the origin of homochirality. Asymmetric autocatalysis triggered by circularly polarized light, chiral minerals such as quartz, chiral organic crystals composed of achiral compounds gave highly enantioenriched pyrimidyl alkanol with absolute configurations corresponding with those of the chiral triggers. Absolute asymmetric synthesis without the intervention of any chiral factor was achieved. Chiral isotopomers acted as chiral triggers of asymmetric autocatalysis.


Assuntos
Álcoois/síntese química , Aldeídos/síntese química , Pirimidinas/síntese química , Alquinos/química , Catálise , Estereoisomerismo , Compostos de Zinco/química
6.
Crit Rev Biotechnol ; 39(3): 366-379, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30700159

RESUMO

Alcohol dehydrogenases are a group of oxidoreductases that specifically use NAD(P)+ or NAD(P)H as cofactors for electron acceptance or donation and catalyze interconversion between alcohols and corresponding carbonyl compounds. In addition to their physiological roles in metabolizing alcohols and aldehydes or ketones, alcohol dehydrogenases have received considerable attention with respect to their symmetry-breaking traits in catalyzing asymmetric reactions and have Accordingly, they have become widely applied in fine chemical synthesis, particularly in the production of chiral alcohols and hydroxyl compounds that are key elements in the synthesis of active pharmaceutical ingredients (API) employed in the pharmaceutical industry. The application of structural bioinformatics to the study of functional enzymes and recent scientific breakthroughs in modern molecular biotechnology provide us with an effective alternative to gain an understanding of the molecular mechanisms involved in asymmetric bioreactions and in overcoming the limitations of enzyme availability. In this review, we discuss molecular mechanisms underlying alcohol dehydrogenase-mediated asymmetric reactions, based on protein structure-function relationships from domain structure to functional active sites. The molecular principles of the catalytic machinery involving stereochemical recognition and molecular interaction are also addressed. In addition, the diversity of enzymatic functions and properties, for example, enantioselectivity, substrate specificity, cofactor dependence, metal requirement, and stability in terms of organic solvent tolerance and thermostability, are also discussed and based on a comparative analysis of high-resolution 3 D structures of representative alcohol dehydrogenases.


Assuntos
Álcool Desidrogenase/química , Biotecnologia/tendências , Biologia Computacional/tendências , Conformação Proteica , Álcool Desidrogenase/genética , Álcoois/síntese química , Álcoois/química , Sequência de Aminoácidos/genética , Biotransformação/genética , Catálise , Humanos , Relação Estrutura-Atividade
7.
Bioorg Chem ; 86: 494-500, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30780018

RESUMO

Bromodomain PHD finger transcription factor (BPTF), a bromodomain-containing protein, plays a crucial role in the regulation of downstream gene expression through the specific recognition of lysine acetylation on bulk histones. The dysfunction of BPTF is closely involved with the development and progression of many human diseases, especially cancer. Therefore, BPTF bromodomain has become a promising drug target for epigenetic cancer therapy. However, unlike BET family inhibitors, few BPTF bromodomain inhibitors have been reported. In this study, by integrating docking-based virtual screening with biochemical analysis, we identified a novel selective BPTF bromodomain inhibitor DCB29 with the IC50 value of 13.2 ±â€¯1.6 µM by homogenous time-resolved fluorescence resonance energy transfer (HTRF) assays. The binding between DCB29 and BPTF was confirmed by NMR and SPR. Molecular docking disclosed that DCB29 occupied the pocket of acetylated H4 peptide substrate and provided detailed SAR explanations for its derivatives. Collectively, DCB29 presented great potential as a powerful tool for BPTF-related biological research and further medicinal chemistry optimization.


Assuntos
Álcoois/farmacologia , Benzamidas/farmacologia , Descoberta de Drogas , Fatores de Transcrição/antagonistas & inibidores , Álcoois/síntese química , Álcoois/química , Benzamidas/síntese química , Benzamidas/química , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Transferência Ressonante de Energia de Fluorescência , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Domínios Proteicos/efeitos dos fármacos , Relação Estrutura-Atividade , Fatores de Transcrição/isolamento & purificação , Fatores de Transcrição/metabolismo
8.
Chem Pharm Bull (Tokyo) ; 67(1): 1-17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30606946

RESUMO

This review reports on the development of new synthetic methods using oxiranyl anions and their application to the synthesis of polycyclic ether marine natural products. Novel iterative and convergent methods for large, complex polycyclic ether structures have been devised. In these, the reactions of sulfonyl-stabilized oxiranyl anions were employed to construct trans-fused polyether ring systems, along with 6-endo cyclization and ring expansion reactions. Total syntheses of polycyclic ether marine toxins, viz. hemibrevetoxin B, gambierol, and gymnocin-A, were achieved based on the oxiranyl anion strategy developed.


Assuntos
Álcoois/química , Produtos Biológicos/síntese química , Éteres/síntese química , Compostos Policíclicos/síntese química , Álcoois/síntese química , Ânions/síntese química , Ânions/química , Produtos Biológicos/química , Compostos de Epóxi/química , Éteres/química , Conformação Molecular , Compostos Policíclicos/química
9.
Chembiochem ; 20(9): 1150-1154, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30600894

RESUMO

Enzymes often convert both physiological and non-physiological substrates with high stereoselectivity; yet, for some enzymes, opposite product chirality is observed. A possible explanation is the existence of hidden specificities becoming apparent when non-physiological substrates confer different substrate-enzyme interactions than the physiological substrate. To test this hypothesis, a series of α-methylated ß-keto esters were converted with Tyl-KR1, a ketoreductase from polyketide synthesis in Streptomyces fradiae. The conversions of six substrates with different physicochemical properties exhibited enantioselectivities ranging from 84 % ee for R,R to 84 % ee for S,S, yet high and uniform diastereoselectivity (anti, d.r.>9:1). The exchange of a single atom, namely an oxygen ester instead of a thioester, led to almost complete loss of enantioselectivity (<5 % ee). An additional S,S-selective binding mode as a hidden specificity in Tyl-KR1 has been identified through molecular modeling and site-directed mutagenesis.


Assuntos
Oxirredutases do Álcool/química , Proteínas de Bactérias/química , Cetonas/química , Oxirredutases do Álcool/genética , Álcoois/síntese química , Álcoois/química , Proteínas de Bactérias/genética , Biocatálise , Mutação , Oxirredução , Estereoisomerismo , Streptomyces/enzimologia , Especificidade por Substrato
10.
J Am Chem Soc ; 140(49): 16976-16981, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30463404

RESUMO

Radical hydrofunctionalization occurs with ease using metal-hydride hydrogen atom transfer (MHAT) catalysis to couple alkenes and competent radicalophilic electrophiles. Traditional two-electron electrophiles have remained unreactive. Herein we report the reductive coupling of electronically unbiased olefins with imines and aldehydes. Iron catalysis allows addition of alkyl-substituted olefins into imines through the intermediacy of free radicals, whereas a combination of catalytic Co(Sal t-Bu, t-Bu) and chromium salts enables a branch-selective coupling of olefins and aldehydes through the formation of a putative alkyl chromium intermediate.


Assuntos
Aldeídos/química , Alcenos/química , Iminas/química , Álcoois/síntese química , Catálise , Técnicas de Química Sintética/métodos , Cromo/química , Cobalto/química , Radicais Livres/química , Ferro/química , Estrutura Molecular , Sulfonamidas/síntese química
11.
J Am Chem Soc ; 140(38): 12290-12295, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30176214

RESUMO

A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and α-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active α-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.


Assuntos
Álcoois/síntese química , Ésteres/química , Furanos/química , Cetonas/química , Nitrocompostos/química , Catálise , Ésteres/síntese química , Neodímio/química , Nitrocompostos/síntese química , Quinazolinas/síntese química , Sódio/química , Solventes/química , Estereoisomerismo , Triazóis/síntese química
12.
Enzyme Microb Technol ; 118: 83-91, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30143204

RESUMO

Biocatalysis has shown tremendous potential in the synthesis of drugs and drug intermediates in the last decade. Screening of novel biocatalysts from the natural genome space is the growing trend to replenish the harsh chemical synthetic routes, commonly used in the pharmaceutical and chemical industry. Here, we report a novel ketoreductase (KERD) and a nitrile reductase isolated from the PCR based library generated from the genome of Rhodococcus ruber and Bacillus subtilis, respectively. Both the proteins are hypothetical in nature as there is no putative homology found in the database, although both the enzymes have significant activity towards the synthesis of chiral alcohols and amines. Enzyme activity over a wide range of substrates (aromatic and aliphatic) for both the novel catalysts was observed. From the unique gene sequence to activity over a broad range of substrate and >99% conversion at higher concentrations (100 mM and above) entitles both the hypothetical enzymes as novel. The novel KERD has shown >99% selectivity for the synthesis of (S)-phenylethanol which makes it a potential candidate for industrial catalysis. The novel nitrile reductase has also shown promising activity for the synthesis of (R)-2-phenylethanolamine, which is a difficult moiety to synthesize chemically. In this report, starting from a homology based library, two highly potent whole cell biocatalysts are obtained.


Assuntos
Bacillus subtilis/enzimologia , Biblioteca Gênica , Oxirredutases/metabolismo , Reação em Cadeia da Polimerase , Rhodococcus/enzimologia , Álcoois/síntese química , Aminas/síntese química , Bacillus subtilis/genética , Bacillus subtilis/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biocatálise , Genoma Bacteriano , Nitrilos/metabolismo , Oxirredutases/genética , Rhodococcus/genética , Rhodococcus/crescimento & desenvolvimento , Estereoisomerismo , Especificidade por Substrato
13.
Inorg Chem ; 57(16): 10160-10169, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30070832

RESUMO

A mononuclear iron(II)-α-hydroxy acid complex [(TpPh,Me)FeII(benzilate)] (TpPh,Me = hydrotris(3-phenyl-5-methylpyrazol-1-yl)borate) of a facial tridentate ligand has been isolated and characterized to explore its catalytic efficiency for aerial oxidation of organic substrates. In the reaction between the iron(II)-benzilate complex and O2, the metal-coordinated benzilate is stoichiometrically converted to benzophenone with concomitant reduction of dioxygen on the iron center. Based on the results from interception experiments and labeling studies, different iron-oxygen oxidants are proposed to generate in situ in the reaction pathway depending upon the absence or presence of an external additive (such as protic acid or Lewis acid). The five-coordinate iron(II) complex catalytically cis-dihydroxylates olefins and oxygenates the C-H bonds of aliphatic substrates using O2 as the terminal oxidant. The iron(II) complex exhibits better catalytic activity in the presence of a Lewis acid.


Assuntos
Alcanos/química , Alcenos/química , Complexos de Coordenação/química , Compostos Ferrosos/química , Ferro/química , Oxigênio/química , Álcoois/síntese química , Benzilatos/síntese química , Benzilatos/química , Catálise , Complexos de Coordenação/síntese química , Compostos Ferrosos/síntese química , Hidroxilação , Ligantes , Modelos Químicos , Oxirredução
14.
CNS Neurol Disord Drug Targets ; 17(6): 448-457, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29972104

RESUMO

BACKGROUND & OBJECTIVE: A series of novel 3-Substituted-1,3,4,5-Tetrahydro-2H-benzo [b] azepine-2-one Derivatives (4, 5, 7, 10, 12, 5a-j, 8a-e) were synthesized from 1,2,3,4-Tetrahydro-1- naphthalenone. The structures of these compounds were confirmed by IR, 1H NMR, 13C NMR, MASS spectra and elemental analysis. Their anticonvulsant activity was evaluated by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test. Compound 4 showed the maximum anticonvulsant activity against the maximal electroshock test (ED50=26.4, PI =3.2) and against the subcutaneous pentylenetetrazol test (ED50=40.2, PI =2.1). CONCLUSION: Possible structure-activity relationship was discussed.


Assuntos
Álcoois , Anticonvulsivantes , Epilepsia/tratamento farmacológico , Álcoois/síntese química , Álcoois/química , Álcoois/farmacologia , Álcoois/uso terapêutico , Animais , Anticonvulsivantes/síntese química , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Modelos Animais de Doenças , Eletrochoque , Epilepsia/induzido quimicamente , Camundongos , Pentilenotetrazol/toxicidade , Relação Estrutura-Atividade
15.
ChemMedChem ; 13(16): 1711-1722, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-29924911

RESUMO

Extension of a structure-activity relationship study of the antitumor cytotoxicity of lipidic dialkynylcarbinols (DACs) is envisaged by formal methinylogation of one of the ethyndiyl moieties of the DAC warhead into the corresponding allenylalkynylcarbinol (AllAC) counterpart. External AllACs were directly obtained by methinylation of the parent DACs with formaldehyde in either the racemic or scalemic series. Isomers containing external progargyl and propynyl motifs were also prepared. Internal AllACs were obtained as racemic statistical mixtures of stereoisomers in two steps from the key C5 -DAC rac-TIPS-C≡C-CH(OH)-C≡CH and aldehydes. Kinetic resolution of the (S)-C5 -DAC in 97 % ee and (R)-C5 -DAC in 99 % ee was achieved by sequential lipase-mediated acetylation/hydrolysis using the Candida antartica lipase (Novozyme 435). The four internal AllAC stereoisomers were prepared by asymmetric methinylation with (R)- or (S)-diphenylprolinol as chiral auxiliary. Cytotoxicity assays on HCT116 cancer cells showed that the most active (eutomeric) external or internal AllAC exhibits an S configuration, a fatty chain length of n=12, and a 50 % inhibitory concentration IC50 ≈1.0 µm.


Assuntos
Álcoois/farmacologia , Alcenos/farmacologia , Alquinos/farmacologia , Antineoplásicos/farmacologia , Álcoois/síntese química , Álcoois/química , Alcenos/síntese química , Alcenos/química , Alquinos/síntese química , Alquinos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Células HCT116 , Humanos , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade
16.
Chem Commun (Camb) ; 54(48): 6088-6104, 2018 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-29770379

RESUMO

In the period 1985 to 1995 applications of biocatalysis, driven by the need for more sustainable manufacture of chemicals and catalytic, (enantio)selective methods for the synthesis of pharmaceutical intermediates, largely involved the available hydrolases. This was followed, in the next two decades, by revolutionary developments in protein engineering and directed evolution for the optimisation of enzyme function and performance that totally changed the biocatalysis landscape. In the same period, metabolic engineering and synthetic biology revolutionised the use of whole cell biocatalysis in the synthesis of commodity chemicals by fermentation. In particular, developments in the enzymatic enantioselective synthesis of chiral alcohols and amines are highlighted. Progress in enzyme immobilisation facilitated applications under harsh industrial conditions, such as in organic solvents. The emergence of biocatalytic or chemoenzymatic cascade processes, often with co-immobilised enzymes, has enabled telescoping of multi-step processes. Discovering and inventing new biocatalytic processes, based on (meta)genomic sequencing, evolving enzyme promiscuity, chemomimetic biocatalysis, artificial metalloenzymes, and the introduction of non-canonical amino acids into proteins, are pushing back the limits of biocatalysis function. Finally, the integral role of biocatalysis in developing a biobased carbon-neutral economy is discussed.


Assuntos
Biocatálise , Enzimas Imobilizadas , Álcoois/síntese química , Aminas/síntese química , Indústria Química/tendências , Enzimas Imobilizadas/química , Enzimas Imobilizadas/genética , Engenharia Metabólica/tendências , Engenharia de Proteínas/tendências , Estereoisomerismo
17.
J Am Chem Soc ; 140(15): 5300-5310, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29547276

RESUMO

A mild and operationally simple copper-catalyzed vinylogous aerobic oxidation of ß,γ- and α,ß-unsaturated esters is described. This method features good yields, broad substrate scope, excellent chemo- and regioselectivity, and good functional group tolerance. This method is additionally capable of oxidizing ß,γ- and α,ß-unsaturated aldehydes, ketones, amides, nitriles, and sulfones. Furthermore, the present catalytic system is suitable for bisvinylogous and trisvinylogous oxidation. Tetramethylguanidine (TMG) was found to be crucial in its role as a base, but we also speculate that it serves as a ligand to copper(II) triflate to produce the active copper(II) catalyst. Mechanistic experiments conducted suggest a plausible reaction pathway via an allylcopper(II) species. Finally, the breadth of scope and power of this methodology are demonstrated through its application to complex natural product substrates.


Assuntos
Álcoois/síntese química , Cobre/química , Ésteres/química , Ar , Álcoois/química , Catálise , Estrutura Molecular , Oxirredução , Estereoisomerismo
18.
J Biotechnol ; 271: 1-7, 2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29452130

RESUMO

Magnetic Fe3O4 nanoparticles were prepared and embedded into the Combi-CLEAs to produce the magnetic Combi-CLEAs in this work. The process for magnetic Combi-CLEAs preparation was optimized, and its properties were investigated. The optimum temperature, thermal stability and optimum pH of magnetic Combi-CLEAs were similar to those of Combi-CLEAs. The catalytic performance of magnetic Combi-CLEAs was tested with the biosynthesis of (S)-ethyl 4-chloro-3-hydroxybutyrate ((S)-CHBE). Magnetic Combi-CLEAs could tolerate higher substrate concentration in the biphasic system. The catalytic efficiency and long-term operational stability of magnetic Combi-CLEAs were obviously superior to those of Combi-CLEAs in both aqueous and biphasic systems. Embedding of magnetic Fe3O4 nanoparticles endowing rigidity contributed to these improvements. Furthermore, the preparation of magnetic Combi-CLEAs was easy, and its recovery during multiple batches of reactions could be fulfilled by magnetic field. Aforementioned advantages make the magnetic Combi-CLEAs hold obvious potential for industrial application.


Assuntos
Álcoois/síntese química , Enzimas Imobilizadas/metabolismo , Álcoois/química , Catálise , Reagentes para Ligações Cruzadas , Estabilidade Enzimática , Enzimas Imobilizadas/química , Nanopartículas de Magnetita/ultraestrutura
19.
ChemSusChem ; 11(5): 881-887, 2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29446547

RESUMO

Cu is a unique catalyst for CO2 electroreduction, since it can catalyze CO2 reduction to a series of hydrocarbons, alcohols, and carboxylic acids. Nevertheless, such Cu catalysts suffer from poor selectivity. High pressure of CO2 is considered to facilitate the activity and selectivity of CO2 reduction. Herein, a new strategy is presented for CO2 reduction with improved C2 H4 selectivity on a Cu catalyst by using CO2 capture materials as the support at ambient pressure. N-doped carbon (Nx C) was synthesized through high-temperature carbonization of melamine and l-lysine. We observed that the CO2 uptake capacity of Nx C depends on both the microporous area and the content of pyridinic N species, which can be controlled by the carbonization temperature (600-800 °C). The as-prepared CuO/Nx C catalysts exhibit a considerably higher C2 H4 faradaic efficiency (36 %) than CuO supported on XC-72 carbon black (19 %), or unsupported CuO (20 %). Moreover, there is a good linear relationship between the C2 H4 faradaic efficiency and CO2 uptake capacity of the supports for CuO. The local high CO2 concentration near Cu catalysts, created by CO2 capture materials, was proposed to increase the coverage of CO intermediate, which is favorable for the coupling of two CO units in the formation of C2 H4 . This study demonstrates that pairing Cu catalysts with CO2 capture supports is a promising approach for designing highly effective CO2 reduction electrocatalysts.


Assuntos
Dióxido de Carbono/química , Cobre/química , Técnicas Eletroquímicas/métodos , Álcoois/síntese química , Ácidos Carboxílicos/síntese química , Catálise , Etilenos/química , Hidrocarbonetos/síntese química , Oxirredução , Temperatura
20.
Chem Rec ; 18(6): 619-658, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29465807

RESUMO

A major proportion of basic cause for human cancer has been linked to widespread environmental pollutants including analogs of polyarenes. Search of an effective therapy can be started with the understanding of the generation of such "carcinogens" and their biological interactions. This review is to discuss the syntheses, structural activities, mechanistic and biological studies of polyarenes such as polycyclic aromatic hydrocarbons (PAHs), polycyclic azaarenes (PAAs) and their thia-analogs (PASH). It also summarizes the mechanism of mutagenicity and tumorigenicity via metabolic interventions producing diol epoxide complexes and eventually formation of DNA adducts. It suggests that inhibition of oxidative reactions and formation of diols and epoxides and unspecific intracellular activation of cytochrome P450 enzymes could be approaches in therapy against such mutagenicity and tumorigenicity. Thus, this review reflects that understanding of molecular mechanisms and activations along with a clinical and translational medicine approach would require achieving both prevention and treatment of this atrocity.


Assuntos
Carcinogênese/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/síntese química , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Álcoois/síntese química , Álcoois/química , Sistema Enzimático do Citocromo P-450/metabolismo , Compostos de Epóxi/síntese química , Compostos de Epóxi/química , Humanos , Estresse Oxidativo/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/química , Relação Estrutura-Atividade
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