Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83.622
Filtrar
1.
J Agric Food Chem ; 67(38): 10782-10790, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31490683

RESUMO

Systematic investigation of cyproconazole, including absolute stereochemistry, fungicidal activity, quantification in two matrixes, and stereoselective degradation in cucumber, are conducted in this study. By virtue of vibrational circular dichroism (VCD) spectroscopy, absolute configurations of four stereoisomers were identified to be (2R,3R)-(+)-, (2R,3S)-(+)-, (2S,3S)-(-)-, and (2S,3R)-(-)-cyproconazoles. Then four stereoisomers exhibited stereoselective fungicidal activities against Fusarium graminearum Schw and Magnaporthe oryzae, and the order of fungicidal activity was (2S,3S)-(-)-stereoisomer > the stereoisomer mixture > (2S,3R)-(-)-stereoisomer > (2R,3R)-(+)-stereoisomer > (2R,3S)-(+)-stereoisomer. Moreover, chiral liquid chromatography-tandem mass spectrometry was used to identify and quantify cyproconazole stereoisomers in soil and cucumber matrixes. Good linearity (R2 ≥ 0.99) and recoveries (86.79-92.47%, RSD ≤ 3.94%) for them were achieved, individually. Furthermore, stereoselective degradation of four cyproconazole stereoisomers was observed in cucumber and the order of degradation rate was (2R,3R)-(+)-cyproconazole > (2S,3S)-(-)-cyproconazole > (2R,3S)-(+)-cyproconazole > (2S,3R)-(-)-cyproconazole. We envision that such systematic assessments of chiral fungicides at an enantiomeric level would provide valuable information in future studies involving enantioselective physiological, metabolic, and toxicological activities.


Assuntos
Fungicidas Industriais/química , Triazóis/química , Alternaria/efeitos dos fármacos , Alternaria/crescimento & desenvolvimento , Cromatografia Líquida de Alta Pressão , Cucumis sativus/química , Contaminação de Alimentos/análise , Fungicidas Industriais/farmacologia , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Poluentes do Solo/química , Poluentes do Solo/farmacologia , Estereoisomerismo , Espectrometria de Massas em Tandem , Triazóis/farmacologia
2.
Chem Pharm Bull (Tokyo) ; 67(8): 775-777, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366826

RESUMO

Nocardia is a potent bacterial producer of bioactive compounds. From a culture of Nocardia beijingensis NBRC 16342, we isolated four aromatic compounds, named beijinchromes A-D (1-4). We purified them by silica gel chromatography and reverse phase HPLC, and identified their structures by NMR and high resolution (HR)-MS analyses. 1, 2, and 4 are novel 1,2,3,8-tetrasubstituted naphthalenes, and 3 is a novel 3,8-disubstituted ortho-naphthoquinone. 1 and 2 exert antioxidant activities, and 3 exhibits antibiotic activity. Remarkably, the putative biosynthetic gene clusters for 1-4 are widely distributed in 37 Nocardia species, implying their potential to produce this family of compounds and important biological functions of beijinchromes.


Assuntos
Hidrocarbonetos Aromáticos/isolamento & purificação , Nocardia/química , Composição de Medicamentos , Hidrocarbonetos Aromáticos/química , Estrutura Molecular , Estereoisomerismo
3.
Anticancer Res ; 39(8): 4479-4483, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366548

RESUMO

BACKGROUND/AIM: The stereo-configuration (R-, S-configuration) of chiral-2-nitroimidazole derivatives alters their radiosensitizing activity. This study aimed at examining the molecular features of these enantiomers by molecular simulation techniques. MATERIALS AND METHODS: A series of 2-nitroimidazole-based radiosensitizer TX-2036 molecules were synthesized, and their profiles were examined using molecular structural analysis such as conformation analysis, molecular orbital analysis, and electrostatic potential analysis. RESULTS: R-configured TXs (TX-2043, -2030, -2036) had a weaker radiosensitizing activity than S-configured TXs (TX-2044, -2031, -2037), and R-compounds had a small minus electrostatic potential (ESP) field in the cyclopentene-1,3-dione region. S-configured TX-2046 had weaker radiosensitizing activity than R-configured TX-2045, and TX-2046 had a small minus ESP field as well as R-configured TX-2043, -2030, - 2036. CONCLUSION: The cyclopentene-1,3-dione involved in the small minus ESP field affected the radiosensitizing activity of the TX-2036 series of molecules.


Assuntos
Desenho de Drogas , Nitroimidazóis/química , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/química , Hipóxia Celular/efeitos dos fármacos , Ciclopentanos/síntese química , Ciclopentanos/química , Humanos , Nitroimidazóis/síntese química , Radiossensibilizantes/síntese química , Eletricidade Estática , Estereoisomerismo , Relação Estrutura-Atividade
4.
J Agric Food Chem ; 67(33): 9362-9370, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31368700

RESUMO

This manuscript presents an effective and robust method for simultaneous stereoselective determination of two pyrethroid insecticides, tetramethrin and α-cypermethrin in different food products by high-performance liquid chromatography. Enantioseparation was carried out using reversed-phase chromatography, and the influences of four polysaccharide-based chiral columns, mobile phase composition, and column temperature on retention were fully investigated. Satisfactory separation was obtained on Chiralpak IG column using acetonitrile-water (75:25, v/v) under isocratic conditions. To extract and purify the target analytes from food matrices, matrix solid-phase dispersion was employed with C18 as dispersant and primary secondary amine as well as graphitized carbon black as cleanup sorbents. Response surface method based on Box-Behnken design was implemented to assist optimization of the extraction variables. Then, method validation was done in real samples including specificity, linearity, sensitivity, trueness, precision, as well as stability, and its analytical performance fulfills the criteria recommended by the European Union SANTE/11945/2015, demonstrating its applicability in studying the stereochemistry of chiral tetramethrin and α-cypermethrin in food products.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Grão Comestível/química , Frutas/química , Inseticidas/química , Piretrinas/química , Verduras/química , Cromatografia de Fase Reversa/métodos , Contaminação de Alimentos/análise , Inseticidas/isolamento & purificação , Piretrinas/isolamento & purificação , Extração em Fase Sólida , Estereoisomerismo
5.
Fitoterapia ; 137: 104287, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386898

RESUMO

Phytochemical investigation of the fruit of Crataegus pinnatifida led to the isolation of four pairs of dihydrobenzofuran neolignan enantiomers (1a/1b-4a/4b) including six new compounds (1a/1b, 2a/2b, 3a and 4a). The enantioseparations of the racemates were achieved successfully by chiral chromatographic column. Their structures were established by comprehensive spectroscopic analyses and the absolute configurations were determined by quantum mechanical calculation of electronic circular dichroism (ECD) spectra. All compounds were evaluated in vitro for their cytotoxicity using human hepatocellular carcinoma Hep3B and HepG2 cells. Among them, it was found that 2a had a selective cytotoxicity against Hep3B cells with IC50 value of 25.47 µM, while the IC50 value of its enantiomer 2b on Hep3B cells was 59.37 µM. These results implied that the absolute configurations of 2a and 2b possessed remarkable influences on their cytotoxicity. Further flow cytometry analysis indicated that 2a performed more significant effect on cell apoptosis compared with its enantiomer 2b.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Crataegus/química , Frutas/química , Lignanas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , China , Células Hep G2 , Humanos , Lignanas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Estereoisomerismo
6.
J Enzyme Inhib Med Chem ; 34(1): 1400-1413, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401897

RESUMO

A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives.


Assuntos
Ácido Benzoico/química , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/efeitos dos fármacos , Desenho de Drogas , Isoenzimas/efeitos dos fármacos , Inibidores da Anidrase Carbônica/síntese química , Domínio Catalítico , Cromatografia Líquida de Alta Pressão , Humanos , Simulação de Acoplamento Molecular , Estereoisomerismo , Relação Estrutura-Atividade
7.
Chem Commun (Camb) ; 55(70): 10480-10483, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31411608

RESUMO

A new enzymatic assay for the preparation of chiral sulfoxides that is enantiocomplementary to the known (S)-enantiomer-reducing activity of methionine sulfoxide reductase A (MsrA) is described. To this end, we have utilized the enzyme DMSO reductase (DmsABC), recently discovered by us being highly upregulated in stationary phase E. coli bacteria.


Assuntos
Sulfóxidos/química , Escherichia coli/metabolismo , Proteínas com Ferro-Enxofre/química , Cinética , Metionina Sulfóxido Redutases/química , Oxirredutases/química , Estereoisomerismo
8.
Chem Pharm Bull (Tokyo) ; 67(7): 729-732, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257328

RESUMO

Intramolecular Büchner reaction of 1-diazo-5-phenylpentan-2-ones followed by oxidation with SeO2 or O2 in the presence of silica gel regioselectively gave 8-formyl-1-tetralones or one-carbon-lacking 1-tetralones, respectively.


Assuntos
Oxigênio/química , Pentanonas/química , Óxidos de Selênio/química , Tetralonas/química , Oxirredução , Estereoisomerismo
9.
J Agric Food Chem ; 67(30): 8303-8311, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31298535

RESUMO

Exposure to chiral pesticides poses many potential health risks. In this study, we examined the impacts of exposure to penconazole and its enantiomers on gut microbiota and metabolic profiles in mice. The relative abundance of microbiota in cecal content significantly changed following exposure to penconazole and its enantiomers. At the genus level, the relative abundances of seven gut microflora were altered following exposure to (-)-penconazole. Both (±)-penconazole and (+)-penconazole caused significant changes in the relative abundances of five gut microflora. In addition, targeted serum metabolomics analysis showed disturbed metabolic profiles following exposure. Respectively, (±)-penconazole, (+)-penconazole, and (-)-penconazole exposure significantly altered the relative levels of 29, 23, and 36 metabolites. In general, exposure to penconazole and its enantiomers caused disorders in gut microbiota and metabolic profiles of mice. The potential health risks of penconazole and its enantiomers now require further evaluation.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos/metabolismo , Praguicidas/química , Praguicidas/farmacologia , Triazóis/química , Triazóis/farmacologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Trato Gastrointestinal/microbiologia , Masculino , Camundongos Endogâmicos ICR , Filogenia , Estereoisomerismo
10.
Chem Commun (Camb) ; 55(65): 9590-9605, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31334709

RESUMO

The study of artificial receptor molecules with the intention to mimic enzyme-substrate binding processes and catalysis in nature has always been a traditional area of research in supramolecular chemistry. Along this line, our group has developed a family of porphyrin cage compounds based on glycoluril and employed these in host-guest binding studies, as components of allosterically controlled self-assembled processes, in which structural changes in the cage upon complexation of a guest or a ligand change binding equilibria, and as enzyme mimics in supramolecular catalysis. In a recently started research program aimed at developing a new molecular approach to long-term data storage, porphyrin cage compounds are studied as molecular machines to encode information into synthetic polymer chains. In this Feature Article we will give an overview of the above aspects of our porphyrin cage compounds and place them in the context of related systems reported in the literature.


Assuntos
Alquinos/química , Materiais Biomiméticos/química , Imidazóis/química , Porfirinas/química , Receptores Artificiais/química , Materiais Biomiméticos/síntese química , Catálise , Imidazóis/síntese química , Ligantes , Metaloporfirinas/síntese química , Metaloporfirinas/química , Nanotecnologia/métodos , Porfirinas/síntese química , Receptores Artificiais/síntese química , Estereoisomerismo , Termodinâmica
11.
Chem Commun (Camb) ; 55(65): 9697-9700, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31347623

RESUMO

An ultra-high sensitivity sensor with the function of chiral signal amplification has been proposed for the enantiomer discrimination of various amino acid enantiomers based on charge transfer (CT)-induced SERS spectroscopy. The introduced TiO2 in this sensor improves the CT behavior and discrimination efficiency distinctly and enantiomeric discrimination is realized even at low concentration.


Assuntos
Compostos de Anilina/química , Nanopartículas Metálicas/química , Compostos de Sulfidrila/química , Triptofano/análise , beta-Ciclodextrinas/química , Ligações de Hidrogênio , Fenilalanina/análise , Fenilalanina/química , Prata/química , Análise Espectral Raman/métodos , Estereoisomerismo , Titânio/química , Triptofano/química , Tirosina/análise , Tirosina/química
12.
Phys Chem Chem Phys ; 21(29): 16017-16031, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31304940

RESUMO

Enterobactin (Ent) is a typical siderophore with strong iron affinity. Its dynamics in its intact form and holo state remains to be studied to understand its role in the in vivo behavior of metal ions and to facilitate its potential application in drug design and environmental remediation. Here, we report molecular dynamics simulations of both Ent enantiomers and their complexes with key actinides (Am3+, Cm3+, Th4+, U4+, Np4+ and Pu4+) to study the folding equilibria of Ent enantiomers and their binding affinity with actinides. For comparison, the ferric cation was also considered. In their neutral state, both enantiomers may exist in their folded and extended states in the aqueous phase with the former more stable owing to the favorable cation-π, π-π, and H-bond interactions. A helicity preference was observed in the folded states of Ent enantiomers, which was solidified when binding with Fe3+ while disrupted when binding with actinides. Upon binding with metal ions, the dynamics of Ent enantiomers exhibited dependence on the metal ions, and appeared to be more flexible in An3+/4+-Ent complexes than in Fe3+-Ent complexes. The conformational analysis and the energy decomposition of M3+/4+-Ent complexes indicated that their distinct conformational variations and dynamic fluxionality are enthalpy driven behaviors and dependent on the nature of the loaded metal ions. The Fe3+-Ent complexes had a more compact conformation, while the relatively loosely bound An3+/4+-Ent complexes allowed solvent water molecules to access the first coordination shell of An3+/4+ and weaken the interaction between An3+/4+ and Ent. This work is expected to enrich our knowledge of the folding equilibria of Ent enantiomers and their An3+/4+-Ent complexes, and contribute to communities that concern the in vivo and in vitro behaviors of Ent enantiomers and actinides.


Assuntos
Elementos da Série Actinoide/química , Enterobactina/química , Modelos Moleculares , Conformação Molecular , Simulação de Dinâmica Molecular , Estereoisomerismo , Termodinâmica
13.
Chem Commun (Camb) ; 55(58): 8402-8405, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31257385

RESUMO

A proof-of-principle for the application of hemi-indigo derivatives as RNA binders with photocontrollable fluorescence is presented. The photoswitch binds to the human immunodeficiency virus type 1 (HIV-1) RNA with a significant light-up effect. The fluorescence of the RNA-bound ligand can be reversibly switched ON and OFF by light without destroying the ligand-RNA associates.


Assuntos
Corantes Fluorescentes/metabolismo , HIV-1/genética , Indóis/metabolismo , RNA/metabolismo , Fluorescência , Corantes Fluorescentes/química , Corantes Fluorescentes/efeitos da radiação , Indóis/química , Indóis/efeitos da radiação , Ligantes , Luz , Estudo de Prova de Conceito , RNA/genética , Elementos de Resposta , Estereoisomerismo
14.
J Chem Ecol ; 45(8): 667-672, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313134

RESUMO

Agriotes ustulatus is an economically important click beetle in Europe. A female-produced pheromone, (E,E)-farnesyl acetate, has been identified and is used for monitoring and detecting males. More recently, a floral lure targeting females with modest, but significant, activity has been described. Based on preliminary data, we hypothesized, that similar to the effects on the congeneric A. brevis, addition of the pheromone to the floral lure should improve female A. ustulatus catches. Also, as click beetles have been reported to respond to white light, we studied possible interactions between visual and chemical cues. In field trials, the addition of the synthetic pheromone to the floral lure resulted in a dramatic increase in the number of females trapped, whereas male catches remained unaffected and equal to those in traps baited with pheromone only. A white visual cue did not influence trap catches. Maximum catches of both sexes of A. ustulatus can be achieved using the pheromone and the floral lure inside the same trap. Furthermore, the compounds can be formulated in a single polyethylene bag dispenser, making handling of the trap easier. Due to a much larger proportion of females in the catch, this improved trap may be a promising tool for semiochemical-based, environmentally sound agricultural practice against this important pest.


Assuntos
Besouros/fisiologia , Feromônios/química , Acroleína/análogos & derivados , Acroleína/química , Acroleína/farmacologia , Animais , Anisóis/química , Anisóis/farmacologia , Comportamento Animal/efeitos dos fármacos , Farneseno Álcool/análogos & derivados , Farneseno Álcool/química , Farneseno Álcool/farmacologia , Feminino , Flores/química , Flores/metabolismo , Controle de Insetos , Masculino , Feromônios/farmacologia , Estereoisomerismo
15.
Fa Yi Xue Za Zhi ; 35(3): 337-343, 2019 Jun.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31282632

RESUMO

Abstract: Methamphetamine (MAMP) is a kind of amphetamine-type stimulants (ATS) which contains one chiral carbon atom in its structure. Therefore a pair of enantiomers, S-(+)-MAMP and R-(-)-MAMP exist. R type and S type methamphetamines possess similar physicochemical properties, but has largely different pharmacological and toxic effects. S-(+)-MAMP is the main component of addictive drug "Ice" at present, seriously affecting human health and public safety. The separation analysis and mechanism of toxic effects discussions on MAMP are the current research focuses. This paper reviews the research progress of separation analysis methods and toxic effects of methamphetamine enantiomers to provide reference for forensic study and forensic practice.


Assuntos
Metanfetamina/química , Estimulantes do Sistema Nervoso Central , Humanos , Estereoisomerismo , Detecção do Abuso de Substâncias
16.
Chem Pharm Bull (Tokyo) ; 67(9): 966-976, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31257308

RESUMO

Honokiol, a biphenolic neolignan isolated from Magnolia officinalis, was reported to have a promising anti-inflammatory activity for the treatment of various diseases. There are many efforts on the synthesis and structure-activity relationship of honokiol derivatives. However, regioselective O-alkylation of honokiol remains a challenge and serves as a tool to provide not only some derivatives but also chemical probes for target identification and mode of action. In this study, we examined the reaction condition for regioselective O-alkylation, in which C2 and C4'-alkylated analogs of honokiol were synthesized and evaluated for inhibitory activity on nitric oxide production and cyclooxygenase-2 expression. Furthermore, we successfully synthesized a potential photoaffinity probe consisting of biotin and benzophenone based on a C4'-alkylated derivative.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Compostos de Bifenilo/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inflamação/tratamento farmacológico , Lignanas/farmacologia , Alquilação , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Humanos , Inflamação/metabolismo , Lignanas/síntese química , Lignanas/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Estereoisomerismo
17.
J Phys Chem Lett ; 10(15): 4197-4202, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31287701

RESUMO

A great deal of thermally instable cis form photoisomerization products will be formed from the thermally stable trans form of the plant sunscreens sinapate esters upon ultraviolet radiation. To reveal the photoisomerization mechanism of the cis-isomer, we explore the photodynamics of a model plant sunscreen methyl sinapate (MS) in the cis form in organic solution. The high photoisomerization quantum yield of the cis-isomer results in the relatively higher photostability of trans-MS. By utilizing femtosecond transient absorption spectroscopy and quantum chemical calculation, we propose that an adiabatic relaxation competes with nonadiabatic relaxation for the excited-state cis form of methyl sinapate. These results suggest that the photoprotection mechanism of the cis form of sinapate esters is significantly different from that of the trans form of sinapate esters and plays an important role in the overall photoprotection effect.


Assuntos
Cinamatos/química , Plantas/química , Protetores Solares/química , Cinética , Processos Fotoquímicos , Estereoisomerismo , Termodinâmica , Raios Ultravioleta
18.
Phytochemistry ; 166: 112061, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299396

RESUMO

(-)-Mesembrine is a chiral alkaloid that features an aryloctahydroindole skeleton and is most commonly found in species of the succulent genus Sceletium. Several Sceletium species are used by various ethnic groups in South Africa to manage disorders of the central nervous system. Binding assays have revealed that mesembrine is a more potent inhibitor of the serotonin transporter (SERT) than fluoxetine (Prozac) which has prompted the commercialization of mesembrine-containing consumer products. The congested all carbon quaternary stereocenter present at the bridgehead of mesembrine has rendered it a compound of interest for research in synthetic chemistry, which has assisted in the absolute configuration of the naturally occurring isomer to be assigned. Accordingly, this review will cover the recent literature pertaining to the distribution, structural elucidation, chemotaxonomy, biosynthesis, organic synthesis, as well as the biological activities of (-)-mesembrine. Recent synthetic procedures of the non-natural enantiomer as well as the racemate are also considered.


Assuntos
Aizoaceae/química , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Psicotrópicos/química , Psicotrópicos/farmacologia , Estereoisomerismo
19.
Chemistry ; 25(51): 11945-11954, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31294500

RESUMO

Acyl transferase from Mycobacterium smegmatis (MsAcT) is a promising biocatalyst because it catalyzes an acyl transfer reaction in aqueous solution, thereby accepting many primary and secondary alcohols as substrates. MsAcT also exhibits high enantioselectivity for a selected number of secondary alcohols. To increase the applicability of this enzyme for the production of optically active compounds, a detailed understanding of the reaction mechanism and the factors that affect enantioselectivity is essential. Herein, quantum chemical calculations are employed to study the reactions of two secondary alcohols, 1-isopropyl propargyl alcohol and 2-hydroxy propanenitrile, for which the enzyme displays opposite enantiopreference, favoring the S enantiomer in the former case and R enantiomer in the latter. A model of the active site has been designed and for both substrates various binding modes are evaluated and the intermediates and transition states along the reaction path are then located. The calculated energy profiles agree with the experimental observations, and reproduce the selectivity outcome. Through a detailed analysis of the geometries of key transition states, insights into the origins of the enantiopreference are obtained.


Assuntos
Álcoois/química , Mycobacterium smegmatis/química , Transferases/metabolismo , Catálise , Domínio Catalítico , Estereoisomerismo
20.
Nat Commun ; 10(1): 2507, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175289

RESUMO

(‒)-Morphine, which is selected as an essential medicine by World Health Organization, is widely applied in the treatment of the pain-related diseases. Due to its synthetically challenging molecular architecture and important clinical role, extensive synthetic studies of morphine-type alkaloids have been conducted. However, catalytic asymmetric total synthesis of (‒)-morphine remains a long-standing challenge. Here, we disclose an efficient enantioselective total synthesis of (‒)-morphine in a longest linear sequence of 16 steps. The key transformation features a highly enantioselective Robinson annulation enabled by our spiro-pyrrolidine catalyst to rapidly construct the densely functionalized cis-hydrodibenzofuran framework containing vicinal stereocenters with an all-carbon quaternary center. This asymmetric approach provides an alternative strategy for the synthesis of (‒)-morphine and its analogues.


Assuntos
Analgésicos Opioides/síntese química , Morfina/síntese química , Benzofuranos/síntese química , Carbono , Estereoisomerismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA