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1.
Talanta ; 233: 122488, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215110

RESUMO

Candida antarctica lipase B (CALB) is a natural biocatalyst with an intrinsically strong chiral environment and a high degree of enantio-selectivity, which is widely used in the separation of racemates. Here, a facile and efficient covalent immobilization approach was utilized to immobilize CALB onto the capillary inner wall as a novel chiral stationary phase to explore and broaden its application in the direct chiral separation by electrochromatography. The obtained CALB immobilized capillary column was characterized by scanning electron microscopy (SEM), fluorescence imaging and Fourier transform infrared spectroscopy (FT-IR). The enantioseparation property of the CALB immobilized capillary column was confirmed by direct chiral separation of several pairs of monoamine neurotransmitter enantiomers in OT-CEC mode. Outstanding enantioseparation performance for three types of monoamine neurotransmitter enantiomers including epinephrine, norepinephrine and phenylephrine was obtained by the CALB immobilized column. Thanks to the effectiveness of covalent bonding method and the intrinsic stability of CALB, the prepared CALB immobilized capillary columns were quite steady and reproducible. The relative standard deviations for retention times of the enantiomers were as follows: for intra-day (n = 5) runs (≤0.25%), inter-day (n = 3) runs (≤0.72%) and between-columns (n = 3) (≤2.42%). After 90 consecutive runs in CEC mode, the CALB immobilized column still exhibited desirable enantionseparation performance.


Assuntos
Eletrocromatografia Capilar , Basidiomycota , Lipase , Espectroscopia de Infravermelho com Transformada de Fourier , Estereoisomerismo
2.
Molecules ; 26(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208623

RESUMO

Furan-2-carboxylic acid was used as a starting material for the synthesis of dehydro-homopilopic acid. Esterification, hydrogenation and enzymatic hydrolysis followed by the reduction of Weinreb amides and a single-step attachment of a 1-methyl-imidazole residue allowed for the concise synthesis of both enantiomers of pilocarpine.


Assuntos
4-Butirolactona/análogos & derivados , Furanos/química , Pilocarpina/síntese química , 4-Butirolactona/síntese química , Amidas/química , Ácidos Carboxílicos/química , Esterificação , Hidrogenação , Hidrólise , Pilocarpina/química , Estereoisomerismo
3.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199610

RESUMO

During the last few decades, pyridazine derivatives have emerged as privileged structures in heterocyclic chemistry, both because of their excellent chemistry and because of their potential applications in medicinal chemistry and optoelectronics. This review is focused on the recent advances in [3 + n] cycloaddition reactions in the pyridazine series as well as their medicinal chemistry and optoelectronic applications over the last ten years. The stereochemistry and regiochemistry of the cycloaddition reactions are discussed. Applications in optoelectronics (in particular, as fluorescent materials and sensors) and medicinal chemistry (in particular, antimicrobials and anticancer) are also reviewed.


Assuntos
Reação de Cicloadição/métodos , Piridazinas/síntese química , Piridazinas/farmacologia , Química Farmacêutica , Eletrônica , Humanos , Fenômenos Ópticos , Piridazinas/química , Estereoisomerismo
4.
Ceska Slov Farm ; 70(2): 51-58, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34237944

RESUMO

The present paper reports the synthesis of a series of seven compounds with a hetero aminopropanol chain. The compounds were prepared by the conversion of 3-alkoxy-4-hydroxyphenyl alkanones with 2-chloromethyl oxirane and subsequent reaction of the products with heterocyclic amines (pyrrolidine, azepane, 4-methylpiperazine and 2-methoxyphenyl piperazine). The target compounds were synthesized in the form of racemates. The purity of the products was confirmed by thin layer chromatography and their IR, UV-VIS and 1H-NMR spectra were recorded. Enantioseparation of the racemic products was accomplished by HPLC on a Chiralpak AD chiral chromatographic column with tris(3,5-dimethylphenyl)carbamate as the chiral selector. The efficiency of enantioseparation was determined in relation to the composition of the mobile phase (hexane : ethanol : methanol : ethylethanamine) and to the structure of the prepared compounds. Baseline separation was achieved with all compounds using mobile phases A (78 : 11 : 11 : 0,1 v/v/v/v) and B (80 : 10 : 10 : 0,1 v/v/v/v), with selectivity factor ranging from 1.07 to 1.42 and resolution from 0.76 to 5.47. The mobile phase containing a higher amount of hexane did not allow for successful enantioseparation of the piperazine derivatives.


Assuntos
Carbamatos , Etanol , Álcoois , Cromatografia Líquida de Alta Pressão , Estereoisomerismo
5.
Ceska Slov Farm ; 70(1): 7-17, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34237948

RESUMO

Since the advent of nitric oxide, diethyl ether, chloroform and cyclopropane, the greatest advancement in the area of general inhalational anesthetics has been achieved by the introduction of fluorinated anesthetics and the relevant chiral techniques. This progress led to marked decrease in mortality rates in anesthesia. In the group of chiral fluorinated compounds, halothane (Fluotan®), isoflurane (Foran®), desflurane (Supran®) and enflurane (Ehran®) are deployed as volatile anesthetics. Chiral anesthetics possess a stereogenic center in their molecules and thus exist as two enantiomers (S)-(+) and (R)-(-). Although these chiral anesthetics are used as racemates, it is crucial to study besides the bioactivities of the racemic compounds also the biological activity and other properties of the particular enantiomers. The present survey discusses the drug category known as inhalational anesthetics in regard to their chiral aspects. These compounds exhibit marked differences between the (R) and (S)-enantiomers in their pharmacodynamics, pharmacokinetics and toxicity. The main analytical technique employed in the enantioseparation of these compounds is gas chromatography (GC). This review lists the individual chiral phases (chiral selectors) used in the enantioseparation as well as in pharmacokinetic studies. The possibilities of preparation of these compounds in their enantiomerically pure form by means of stereoselective synthesis are also mentioned.


Assuntos
Anestésicos Inalatórios , Isoflurano , Enflurano , Halotano , Estereoisomerismo
6.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205002

RESUMO

Numerous chemical compounds of high practical importance, such as drugs, fertilizers, and food additives are being commercialized as racemic mixtures, although in most cases only one of the isomers possesses the desirable properties. As our understanding of the biological actions of chiral compounds has improved, the investigation of the pharmacological and toxicological properties has become more and more important. Chirality has become a major issue in the pharmaceutical industry; therefore, there is a continuous demand to extend the available analytical methods for enantiomeric separations and enhance their efficiency. Direct liquid chromatography methods based on the application of chiral stationary phases have become a very sophisticated field of enantiomeric separations by now. Hundreds of chiral stationary phases have been commercialized so far. Among these, macrocyclic glycopeptide-based chiral selectors have proved to be an exceptionally useful class of chiral selectors for the separation of enantiomers of biological and pharmacological importance. This review focuses on direct liquid chromatography-based enantiomer separations, applying macrocyclic glycopeptide-based chiral selectors. Special attention is paid to the characterization of the physico-chemical properties of these macrocyclic glycopeptide antibiotics providing detailed information on their applications published recently.


Assuntos
Antibacterianos/química , Glicopeptídeos/química , Compostos Macrocíclicos/química , Cromatografia Líquida , Estrutura Molecular , Fenômenos Físicos , Estereoisomerismo
7.
J Org Chem ; 86(12): 8274-8285, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34061532

RESUMO

Despite having the capability to construct benzo-fused heterocycles in complete atom economy and high chemo-, regio-, enantio-, and diastereoselectivities, intramolecular Friedel-Crafts epoxide arene cyclization (IFCEAC) remains underutilized in organic synthesis. The wide adaptation of this powerful Csp2-Csp3 bond-forming reaction, therefore, requires a broad understanding of the substrate scope to better impact heterocycle synthesis. Along this line, we investigated the applicability of IFCEAC for the synthesis of 1,7- and 1,2-fused indoles. In this article, we report the results of our systematic investigation into the scope and limitations of the first examples of the hexafluoro-2-propanol (HFIP)-mediated IFCEAC of readily accessible indolyl-N-tethered epoxides. We observed that the nature and position of the indole and epoxide substituents and the tether length separating these two reacting moieties have strong effects on the cyclization. This mild and transition-metal-free protocol delivered pyrrolo[3,2,1-ij]quinolin-5-ols in moderate to good yields from substrates bearing both a methylene linker that connects the indole and epoxide moieties and an electron-rich indole carbocyclic ring. Notably, the reactions required the presence of a π-activating aryl substituent on the reacting epoxide carbon atom. Interestingly, replacing the methylene tether with an ethylene unit resulted in regioswitching, which delivered the corresponding tetrahydropyrido[1,2-a]indol-8-ols in good to high yields. We could also successfully extend this methodology to pyrrolyl-N-tethered epoxides for a very high-yielding synthesis of tetrahydroindolizin-7-ols.


Assuntos
Compostos de Epóxi , Indóis , Ciclização , Estrutura Molecular , Propanóis , Estereoisomerismo
8.
Toxins (Basel) ; 13(5)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064772

RESUMO

Ergot alkaloids are mycotoxins formed by fungi of the Claviceps genus, which are some of the most common contaminants of food and feed worldwide. These toxins are a structurally heterogeneous group of compounds, sharing an ergoline backbone. Six structures and their corresponding stereoisomers are typically quantified by either HPLC-FLD or HPLC-MS/MS and the values subsequently summed up to determine the total ergot alkaloid content. For the development of a screening method targeting all ergot alkaloids simultaneously, the alkaloids need to be transferred to one homogeneous structure: a lysergic acid derivative. In this study, two promising cleaving methods-acidic esterification and hydrazinolysis-are compared, using dihydroergocristine as a model compound. While the acidic esterification proved to be unsuitable, due to long reaction times and oxidation sensitivity, hydrazinolysis reached a quantitative yield in 40‒60 min. Parallel workup of several samples is possible. An increasing effect on the reaction rate by the addition of ammonium iodide was demonstrated. Application of hydrazinolysis to a major ergot alkaloid mix solution showed that all ergopeptines were cleaved, but ergometrine/-inine was barely affected. Still, hydrazinolysis is a suitable tool for the development of a sum parameter screening method for ergot alkaloids in food and feed.


Assuntos
Claviceps/metabolismo , Alcaloides de Claviceps/análise , Micotoxinas/análise , Cromatografia Líquida de Alta Pressão , Alcaloides de Claviceps/química , Hidrazinas/química , Micotoxinas/química , Estereoisomerismo , Espectrometria de Massas em Tandem
9.
Food Chem ; 361: 130130, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062458

RESUMO

A comprehensive data collection of mass spectral and gas chromatographic data of a series of esters of diastereomeric menthols (menthol, isomenthol, neomenthol, and neoisomenthol), in total 150 chemical entities, obtained by GC-MS on commonly used capillary columns of different polarity (non-polar HP-5MS and polar HP-Innowax), was created. Also, MS libraries containing electron ionization MS recorded on single quadrupole as well as on quadrupole ion-trap mass detectors together with the RIs on non-polar and polar columns were compiled (available as supplementary materials). The results point out to frequent misidentification of neoisomenthyl acetate as isomenthyl acetate in the literature, and the means of how to resolve this issue was suggested. The outcomes of this study provide chemists and food technologists with a useful tool in the field of food analysis of compounds with important food aroma properties.


Assuntos
Ésteres/química , Mentol/química , Acetatos/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Estereoisomerismo
10.
J Org Chem ; 86(12): 8295-8307, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34100288

RESUMO

The reactivity of "furan-ynes" in combination with pyridine and quinoline N-oxides in the presence of a Au(I) catalyst, has been studied, enabling the synthesis of three different heterocyclic scaffolds. Selective access to two out of the three possible products, a dihydropyridinone and a furan enone, has been achieved through the fine-tuning of the reaction conditions. The reactions proceed smoothly at room temperature and open-air, and were further extended to a broad substrate scope, thus affording functionalized dihydropyridinones and pyranones.


Assuntos
Ouro , Óxidos , Catálise , Ciclização , Furanos , Estrutura Molecular , Estereoisomerismo
11.
J Chromatogr A ; 1651: 462318, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34161834

RESUMO

BMS-962212, a parenteral Factor XIa inhibitor, was scaled-up for toxicity studies. Two steps of supercritical fluid chromatography (SFC) were developed for the chiral resolution of the penultimate and achiral purification of final active pharmaceutical ingredient (API), BMS-962212. A robust SFC process using Chiralcel OD-H with methanol-acetonitrile as modifier in CO2 was established to achieve a stable and uninterrupted operation with reduced mobile phase viscosity and system pressure drop. More than 230 g of the racemic penultimate was chirally resolved to reach >99% chiral purity, ready for final tert-butyl ester deprotection to provide the API. There were a significant number of impurities in BMS-962212 generated from the final step that needed to be removed. In contrast to conventional SFC conditions, an SFC method exploiting water and ammonia as additives in both the mobile phase and sample solution was developed to accomplish purification and desalting (i.e. removing TFA) of the zwitterionic API in one step. Water as an additive eliminated salt precipitation and improved the resolution while ammonia contributed to the desalting, details of which will be discussed in this article. A throughput of 2 g/h was achieved, and >80 g of the crude API was purified. The same strategy was applied to another Factor XIa API (compound A) and its penultimate.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Fator XIa/isolamento & purificação , Preparações Farmacêuticas/isolamento & purificação , Água/química , Acetonitrilas , Amônia/química , Cromatografia Líquida de Alta Pressão , Fator XIa/química , Isoquinolinas/química , Metanol/química , Preparações Farmacêuticas/química , Estereoisomerismo , para-Aminobenzoatos/química
12.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066468

RESUMO

NR+ is a highly effective vitamin B3 type supplement due to its unique ability to replenish NAD+ levels. While NR+ chloride is already on the market as a nutritional supplement, its synthesis is challenging, expensive, and low yielding, making it cumbersome for large-scale industrial production. Here we report the novel crystalline NR+ salts, d/l/dl-hydrogen tartrate and d/l/dl-hydrogen malate. Their high-yielding, one-pot manufacture does not require specific equipment and is suitable for multi-ton scale production. These new NR+ salts seem ideal for nutritional applications due to their bio-equivalence compared to the approved NR+ chloride. In addition, the crystal structures of all stereoisomers of NR+ hydrogen tartrate and NR+ hydrogen malate and a comparison to the known NR+ halogenides are presented.


Assuntos
Aditivos Alimentares/química , Tecnologia de Alimentos/métodos , Niacinamida/análogos & derivados , Niacinamida/química , Compostos de Piridínio/química , Ânions , Técnicas de Química Sintética , Cloretos , Cristalização , Suplementos Nutricionais , Hidrogênio/química , Espectroscopia de Ressonância Magnética , Malatos/química , Oxirredução , Sais , Estereoisomerismo , Tartaratos/química , Difração de Raios X
13.
Molecules ; 26(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067439

RESUMO

Ezetimibe is a well-known drug that lowers blood cholesterol levels by reducing its absorption in the small intestine when joining to Niemann-Pick C1-like protein (NPC1L1). A ligand-based study on ezetimibe analogues is reported, together with one-hit synthesis, highlighted in the study. A convenient asymmetric synthesis of (2S,3S)-N-α-(R)-methylbenzyl-3-methoxycarbonylethyl-4-methoxyphenyl ß-lactam is described starting from Baylis-Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent inversion of ester and acid functionality paves the way to the lactam core after monodebenzylation and lactam formation. It also shows interesting results when it comes to a pharmacophore study based on ezetimibe as the main ligand in lowering blood cholesterol levels, revealing which substituents on the azetidine-2-one ring are more similar to the ezetimibe skeleton and will more likely bind to NPC1L1 than ezetimibe.


Assuntos
Técnicas de Química Sintética , Desenho de Fármacos , Ezetimiba/análogos & derivados , Ezetimiba/síntese química , Alelos , Amidas/química , Aminoácidos/química , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/síntese química , Colesterol/sangue , Humanos , Ligantes , Espectroscopia de Ressonância Magnética , Proteínas de Membrana Transportadoras/metabolismo , Simulação de Acoplamento Molecular , Piridinas/química , Estereoisomerismo
14.
Environ Sci Technol ; 55(13): 9087-9096, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34106693

RESUMO

Bifenthrin (BF) is a widely used pyrethroid that has been frequently detected in surface waters. Previous studies indicated that BF had antiestrogenic activity in zebrafish embryos but estrogenic activity in posthatch fish. To determine whether age-related differences in metabolism contribute to the endocrine effects in developing fish, embryos from zebrafish and Japanese medaka were exposed to BF before and after liver development. Since the commercial mixture of BF is an isomer-enriched product containing two enantiomers (1R-cis-BF and 1S-cis-BF), enantioselective metabolism was also evaluated. The estrogenic metabolite, 4-hydroxybifenthrin (4-OH-BF) was identified in zebrafish embryos, and formation was higher in animals after liver development (>48 hpf). Treatments with ß-glucuronidase indicated that 4-OH-BF underwent conjugation in embryos. Formation was reduced by cotreatment of the cytochrome P450 (CYP450) inhibitor, ketoconazole. Formation of 4-OH-BF was greater when treated with 1R-cis-BF compared to the S-enantiomer. However, metabolites were not observed in medaka embryos. These data indicate enantioselective oxidation of BF to an estrogenic metabolite occurs in zebrafish embryos and, since it is increased after liver development, may partially explain estrogenic activity observed in older animals. The lack of activity in medaka suggests species-specific effects with BF metabolism and may influence risk assessment strategies in wildlife.


Assuntos
Inseticidas , Oryzias , Piretrinas , Poluentes Químicos da Água , Animais , Inseticidas/toxicidade , Piretrinas/toxicidade , Estereoisomerismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
15.
Nanoscale ; 13(26): 11325-11333, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34190303

RESUMO

Peptide soft materials belong to an emerging branch of materials sciences due to their growing importance as responsive materials in diagnostics, therapeutics, and biomedical applications. The diversity provided by easily modifiable peptide sequences can be further increased by introducing nonnatural amino acids such as cyclic ß-amino acids, leading to the formation of foldamers. Moreover, it is possible to combine peptide chains with other polymers, aromatic compounds, etc. to create hybrids with completely new properties and applications. In this review, we focus on the cis/trans enantiomers of three cyclic ß-amino acids: 2-aminocyclobutane-1-carboxylic acid (ACBC), 2-aminocyclopentane-1-carboxylic acid (ACPC) and 2-aminocyclohexane-1-carboxylic acid (ACHC). The peptides discussed here either contain exclusively ß-amino acids or are α,ß-peptides, and they undergo self-assembly by forming different interactions that lead to the creation of well-defined nanostructures.


Assuntos
Nanoestruturas , Peptídeos , Aminas , Sequência de Aminoácidos , Estereoisomerismo
16.
Nucleic Acids Res ; 49(11): 6114-6127, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34125895

RESUMO

Dynamic DNA nanodevices represent powerful tools for the interrogation and manipulation of biological systems. Yet, implementation remains challenging due to nuclease degradation and other cellular factors. Use of l-DNA, the nuclease resistant enantiomer of native d-DNA, provides a promising solution. On this basis, we recently developed a strand displacement methodology, referred to as 'heterochiral' strand displacement, that enables robust l-DNA nanodevices to be sequence-specifically interfaced with endogenous d-nucleic acids. However, the underlying reaction - strand displacement from PNA-DNA heteroduplexes - remains poorly characterized, limiting design capabilities. Herein, we characterize the kinetics of strand displacement from PNA-DNA heteroduplexes and show that reaction rates can be predictably tuned based on several common design parameters, including toehold length and mismatches. Moreover, we investigate the impact of nucleic acid stereochemistry on reaction kinetics and thermodynamics, revealing important insights into the biophysical mechanisms of heterochiral strand displacement. Importantly, we show that strand displacement from PNA-DNA heteroduplexes is compatible with RNA inputs, the most common nucleic acid target for intracellular applications. Overall, this work greatly improves the understanding of heterochiral strand displacement reactions and will be useful in the rational design and optimization of l-DNA nanodevices that operate at the interface with biology.


Assuntos
DNA/química , Ácidos Nucleicos Heteroduplexes/química , Ácidos Nucleicos Peptídicos/química , Cinética , RNA/química , Estereoisomerismo , Termodinâmica
17.
J Chromatogr A ; 1651: 462309, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34147835

RESUMO

A regioisomeric mixture of the nucleoside derivative, Intermediate 1, required resolution by preparative supercritical fluid chromatography (SFC) in order to obtain the desired regioisomer as a key intermediate in a STING agonist program. Various chiral columns and solvents including methanol, acetonitrile, isopropanol, and the mixture of acetonitrile and isopropanol as organic modifiers in carbon dioxide at different temperatures were screened to obtain the best regioisomeric resolution. A key issue associated with interconversion between the regioisomers via silyl migration during purification was investigated in methanol, acetonitrile, and the mixture of acetonitrile and isopropanol, and the optimal organic modifier in CO2 was established to mitigate the interconversion to an acceptable level (<5%). Taking into account peak resolution, throughput, interconversion and operation robustness, an efficient SFC method for large-scale purification was successfully developed and scaled up onto a 5 cm I. D. Chiralcel OJ-H column using 25% acetonitrile: isopropanol [1:1 (v/v)] with 0.1% ammonium hydroxide as the modifier in CO2 at a total flow rate of 270 mL/min and a temperature of 30°C. In addition, continual evaporation (i.e. every hour) of the desired isomer fraction stream post-separation ensured minimal further interconversion. A total of 258 grams were separated at a high throughput of 8.6 g/h. Regioisomeric purity of the desired isomer of Intermediate 1 was ≥98.2% and the recovery was ≥90.2%. A similar purification strategy was applied to the regioisomeric resolution of Intermediate 2, an analog of Intermediate 1. In total, 1028 grams of Intermediate 2 were processed at a high throughput of 12.5 g/h on a Viridis BEH 2-EP column. The regioisomeric purity of the desired isomer was ≥96.8% and the recovery was ≥90.7%.


Assuntos
Adjuvantes Imunológicos/isolamento & purificação , Cromatografia com Fluido Supercrítico , Proteínas de Membrana/agonistas , Adjuvantes Imunológicos/química , Hidróxido de Amônia/química , Dióxido de Carbono/química , Proteínas de Membrana/genética , Metanol/química , Solventes/química , Estereoisomerismo , Temperatura
18.
J Chromatogr A ; 1651: 462338, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34153735

RESUMO

ß-Cyclodextrin can be functionalized by derivation of reactive hydroxyl on the ring due to its special chiral environment and structural characteristics, which can be used to identify or separate a variety of chiral substance. In this manuscript, a series of excellent chiral stationary phases for high-performance liquid chromatography were developed for enantioseparation by using anhydride modified ß-cyclodextrin bearing chiral (R/S)-α-phenethylamine or (S)-(+)-2-amino-1-propanol. They were characterized by elemental analysis, Fourier transform infrared spectra (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and BET. These chiral stationary phases presented good resolution and repeatability, about 17 kinds of enantiomers were effectively separated. And most of enantiomers were separated better than those reported in the literature in the same both normal and reversed phase modes. The RSD values of Rs for repeatability and column-to-column were below 0.44% and 2.83%, respectively. All results revealed that these new CSPs show great prospect for chiral separation in actual applications.


Assuntos
Anidridos/química , Cromatografia Líquida/métodos , beta-Ciclodextrinas/química , Cromatografia Líquida de Alta Pressão/métodos , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Estereoisomerismo
19.
J Chromatogr A ; 1651: 462308, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34157473

RESUMO

Preparative chiral separations are carried out using chiral stationary-phases (CSP) employing isocratic composition mode to take advantage of stacking multiple injections within a single continuous operation. Development of the separation method, however, is not conducted directly in the preparative systems. Chromatographic systems at analytical scale are set up to screen multiple CSPs with various mobile-phases (MP) to detect a suitable CSP-MP combination. For faster method screening, solvent-gradients are implemented - operating from low to higher modifier composition, e.g. 5 to 70%. Once the right CSP-MP pair is detected, the isocratic method for preparative separation is developed through further experimental trials in the analytical system. The scope of the trial steps is generally limited to detecting a "good-enough" separation condition through one or two isocratic experiments. Ideally, the analyst should scout all possible isocratic conditions to detect the most suitable method; which, however, is not possible in high-throughput separation laboratories. In this report we demonstrate the utility of a simple set of algebraic equations, supported by an experimental protocol, in generating complete isocratic method options based on minimum number of experimental trials. The approach presented here was developed for chiral separation with supercritical-fluid chromatography. We also suggest an approach to identify an isocratic composition for the purification step. The process proposed in this report should be useful in developing better preparative separation methods in high-throughput laboratories.


Assuntos
Técnicas de Química Analítica/métodos , Cromatografia com Fluido Supercrítico , Modelos Químicos , Solventes/química , Estereoisomerismo
20.
Nat Commun ; 12(1): 3268, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075034

RESUMO

Halocyclization of alkenes is a powerful bond-forming tool in synthetic organic chemistry and a key step in natural product biosynthesis, but catalyzing halocyclization with high enantioselectivity remains a challenging task. Identifying suitable enzymes that catalyze enantioselective halocyclization of simple olefins would therefore have significant synthetic value. Flavin-dependent halogenases (FDHs) catalyze halogenation of arene and enol(ate) substrates. Herein, we reveal that FDHs engineered to catalyze site-selective aromatic halogenation also catalyze non-native bromolactonization of olefins with high enantioselectivity and near-native catalytic proficiency. Highly selective halocyclization is achieved by characterizing and mitigating the release of HOBr from the FDH active site using a combination of reaction optimization and protein engineering. The structural origins of improvements imparted by mutations responsible for the emergence of halocyclase activity are discussed. This expansion of FDH catalytic activity presages the development of a wide range of biocatalytic halogenation reactions.


Assuntos
Alcenos/metabolismo , Biocatálise , Flavinas/metabolismo , Oxirredutases/metabolismo , Alcenos/química , Domínio Catalítico/genética , Ciclização , Ensaios Enzimáticos , Flavinas/química , Halogenação , Cinética , Simulação de Acoplamento Molecular , Mutagênese , Mutação , Oxirredutases/química , Oxirredutases/genética , Engenharia de Proteínas , Estereoisomerismo
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