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1.
Nat Commun ; 12(1): 804, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547322

RESUMO

Evolution of xeno nucleic acid (XNA) world essentially requires template-directed synthesis of XNA polymers. In this study, we demonstrate template-directed synthesis of an acyclic XNA, acyclic L-threoninol nucleic acid (L-aTNA), via chemical ligation mediated by N-cyanoimidazole. The ligation of an L-aTNA fragment on an L-aTNA template is significantly faster and occurs in considerably higher yield than DNA ligation. Both L-aTNA ligation on a DNA template and DNA ligation on an L-aTNA template are also observed. High efficiency ligation of trimer L-aTNA fragments to a template-bound primer is achieved. Furthermore, a pseudo primer extension reaction is demonstrated using a pool of random L-aTNA trimers as substrates. To the best of our knowledge, this is the first example of polymerase-like primer extension of XNA with all four nucleobases, generating phosphodiester bonding without any special modification. This technique paves the way for a genetic system of the L-aTNA world.


Assuntos
Amino Álcoois/metabolismo , Butileno Glicóis/metabolismo , DNA/genética , Imidazóis/química , Ácidos Nucleicos/síntese química , RNA/genética , Amino Álcoois/química , Pareamento de Bases , Biocatálise , Butileno Glicóis/química , Cátions Bivalentes , DNA/química , DNA/metabolismo , Primers do DNA/química , Primers do DNA/metabolismo , Manganês/química , Manganês/metabolismo , Conformação de Ácido Nucleico , RNA/química , RNA/metabolismo , Soluções
2.
Parasitol Res ; 119(10): 3503-3515, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32772176

RESUMO

Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity against Plasmodium falciparum and was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds against Babesia divergens, and against promastigotes, and amastigotes stages of Leishmania in vitro. It inhibited the in vitro growth of two African animal strains of Trypanosoma but was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.


Assuntos
Amino Álcoois/farmacologia , Antiprotozoários/farmacologia , Amino Álcoois/síntese química , Amino Álcoois/química , Animais , Antiprotozoários/síntese química , Antiprotozoários/química , Babesia/efeitos dos fármacos , Babesia/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Modelos Animais de Doenças , Leishmania/efeitos dos fármacos , Leishmania/crescimento & desenvolvimento , Estágios do Ciclo de Vida/efeitos dos fármacos , Camundongos , Plasmodium/efeitos dos fármacos , Plasmodium/crescimento & desenvolvimento , Infecções por Protozoários/tratamento farmacológico , Infecções por Protozoários/parasitologia , Resultado do Tratamento , Trypanosoma/efeitos dos fármacos , Trypanosoma/crescimento & desenvolvimento , Células Vero
3.
Nat Protoc ; 15(7): 2203-2229, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32541940

RESUMO

Determining enantiomeric excess (e.e.) in chiral compounds is key to development of chiral catalyst auxiliaries and chiral drugs. Here we describe a sensitive and robust fluorescence-based assay for determining e.e. in mixtures of enantiomers of 1,2- and 1,3-diols, chiral amines, amino alcohols, and amino-acid esters. The method is based on dynamic self-assembly of commercially available chiral amines, 2-formylphenylboronic acid, and chiral diols in acetonitrile to form fluorescent diastereomeric complexes. Each analyte enantiomer engenders a diastereomer with distinct fluorescence wavelength/intensity originating from enantiopure fluorescent ligands. In this assay, enantiomers of amines and amine derivatives assemble with diol-type ligands containing a binaphthol moiety (BINOL and VANOL), whereas diol enantiomers form complexes with the enantiopure amine-type fluorescent ligand tryptophanol. The differential fluorescence is utilized to determine the amount of each enantiomer in the mixture with an error of <1% e.e. This method enables high-throughput real-time evaluation of enantiomeric/diastereomeric excess (e.e./d.e.) and product yield of crude asymmetric reaction products. The procedure comprises high-throughput liquid dispensing of three components into 384-well plates and recording of fluorescence using an automated plate reader. The approach enables scaling up the screening of combinatorial libraries and, together with parallel synthesis, creates a robust platform for discovering chiral catalysts or auxiliaries for asymmetric transformations and chiral drug development. The procedure takes ~4-6 h and requires 10-20 ng of substrate per well. Our fluorescence-based assay offers distinct advantages over existing methods because it is not sensitive to the presence of common additives/impurities or unreacted/incompletely utilized reagents or catalysts.


Assuntos
Aminas/química , Amino Álcoois/química , Avaliação Pré-Clínica de Medicamentos/métodos , Ensaios de Triagem em Larga Escala/métodos , Estereoisomerismo
4.
Molecules ; 25(3)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32046110

RESUMO

In this report, we describe the synthetic elaboration of the easily available enantiomerically pure ß-amino alcohols. Attempted direct substitution of the hydroxyl group by azido-functionality in the Mitsunobu reaction with hydrazoic acid was inefficient or led to a diastereomeric mixture. These outcomes resulted from the participation of aziridines. Intentionally performed internal Mitsunobu reaction of ß-amino alcohols gave eight chiral aziridines in 45-82% yield. The structural and configuration identity of products was confirmed by NMR data compared to the DFT calculated GIAO values. For 1,2,3-trisubstituted aziridines slow configurational inversion at the endocyclic nitrogen atom was observed by NMR at room temperature. Moreover, when aziridine was titrated with Zn(OAc)2 under NMR control, only one of two N-epimers directly participated in complexation. The aziridines underwent ring opening with HN3 to form the corresponding azido amines as single regio- and diastereomers in 90-97% yield. Different results were obtained for 1,2-disubstituted and 1,2,3-trisubstituted aziridines. For the later aziridines ring closure and ring opening occurred at different carbon stereocenters, thus yielding products with two inverted configurations, compared to the starting amino alcohol. The 1,2-disubstituted aziridines produced azido amines of the same configuration as the starting ß-amino alcohols. To obtain a complete series of diastereomeric vic-diamines, we converted the amino alcohols into cyclic sulfamidates, which reacted with sodium azide in SN2 reaction (25-58% overall yield). The azides obtained either way underwent the Staudinger reduction, giving a series of six new chiral vic-diamines of defined stereochemistries.


Assuntos
2,2'-Dipiridil/química , Amino Álcoois/química , Diaminas/química , Aminas/química , Azidas/química , Aziridinas/química , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Estereoisomerismo
5.
Chemistry ; 26(2): 379-383, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31609031

RESUMO

Peptide alcohols are clinically important compounds that are underexplored in structure-activity relationship (SAR) studies in drug discovery. One reason for this underutilization is that current syntheses are laborious and time consuming. Herein, we describe the preparation and utility of Rink, Ramage, and Sieber-chloride resins, which enables the use of a general, easy and practical method for the attachment of fluorenylmethoxycarbonyl (Fmoc)-amino alcohols to a solid support, in the synthesis of peptide alcohols. This method is the first straightforward Fmoc/tBu synthesis of peptide alcohols starting from a pre-loaded resin. The synthesized peptide alcohols can be detached from the linkers through conventional methods. Treatment with trifluoroacetic acid (TFA) (95 %) and scavengers such as triisopropylsilane and water for 2 h is sufficient to obtain a fully deprotected peptide alcohol, while treatment with 20 % hexafluoroisopropanol in dichloromethane renders a fully protected peptide alcohol that can be further modified at the C-terminus. As examples, the new resins were used in straightforward, relatively rapid syntheses of the peptide alcohols octreotide, alamethicin, and a segment of trichogin GA IV, as well as the first synthesis of stapled peptide alcohols.


Assuntos
Amino Álcoois/química , Peptídeos/química , Peptídeos/síntese química , Fenilalanina/análogos & derivados , Fenilalanina/química , Poliestirenos/química , Ácido Trifluoracético/química
6.
J Sep Sci ; 43(3): 648-656, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31705790

RESUMO

A simple, rapid, capillary zone electrophoresis method was developed and validated for the analysis of two novel aminoalkanol derivatives (I) and (II) of 1,7-diethyl-8,9-diphenyl-4-azatricyclo[5.2.1.02,6 ]dec-8-ene-3,5,10-trione, which were found in earlier studies as potential anticancer drugs. Samples were analyzed to demonstrate the specificity and stability indicating ability of the developed method. The samples were extracted using n-hexane-ethyl acetate mixture in the ratio of 90:10. Electrophoretic separation was performed on a eCAP fused silica capillary (37 cm length, 50 µm inside diameter) with a 50 mM tetraborate buffer as a background electrolyte adjusted to pH = 2.5. The separation time of (I) and (II) was achieved within 7 min. In addition, analysis of the two compounds in the serum was conducted. Limits of detection of (I) and (II) by UV absorbance at 200 nm were achieved in the range of 87.4-92.1 ng/mL. The sufficient recovery was observed in the range of 90.3-99.8%. The quantification limits for the compounds (I) and (II) were in the range of 279.71-291.03 ng/mL, respectively. The method has been successfully applied to the analysis of compounds (I) and (II) in serum samples.


Assuntos
Amino Álcoois/sangue , Antineoplásicos/sangue , Amino Álcoois/química , Antineoplásicos/química , Estabilidade de Medicamentos , Eletroforese Capilar , Humanos , Estrutura Molecular , Soluções , Água/química
7.
Molecules ; 25(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861609

RESUMO

A library of 1,2-aminoalcohol derivatives with a neoisopulegol-based octahydrobenzofuran core was developed and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The allylic chlorination of (+)-neoisopulegol, derived from natural (-)-isopulegol followed by cyclization, gave the key methyleneoctahydrobenzofuran intermediate. The stereoselective epoxidation of the key intermediate and subsequent oxirane ring opening with primary amines afforded the required 1,2-aminoalcohols. The ring closure of the secondary amine analogues with formaldehyde provided spiro-oxazolidine ring systems. The dihydroxylation of the methylenetetrahydrofuran moiety with OsO4/NMO (4-methylmorpholine N-oxide) resulted in the formation of a neoisopulegol-based diol in a highly stereoselective reaction. The antimicrobial activity of both the aminoalcohol derivatives and the diol was also explored.


Assuntos
Amino Álcoois/síntese química , Anti-Infecciosos/síntese química , Benzofuranos/química , Monoterpenos Cicloexânicos/química , Amino Álcoois/química , Amino Álcoois/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Benzaldeídos/química , Catálise , Ciclização , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organometálicos/química
8.
Analyst ; 144(24): 7468-7477, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31710318

RESUMO

This study deals with the nonaqueous capillary electrophoretic enantioseparation of twenty-two amino alcohol drugs with a maltobionic acid (MA)-based ionic liquid (tetramethylammonium maltobionic acid, TMA-MA) as the novel chiral selector. In consideration of the poor solubility of MA in organic solvents, we managed to transform MA into ionic liquids (ILs) for the first time. Interestingly, this chiral selector exhibited powerful enantioselectivity towards the model analytes in company with boric acid. Systematical experiments were carried out to investigate the influence of concentration of TMA-MA, boric acid and tris (hydroxymethyl) aminomethane (Tris) as well as applied voltage on the enantioseparation. A great majority of enantiomers (except labetalol) were baseline separated under the optimized conditions and the effect of the molecular structure of amino alcohol drugs on the chiral separation was discussed. In addition, electrophoretic experiments, nuclear magnetic resonance (NMR), mass spectrometry (MS) and molecular modeling with the Gaussian program were employed to demonstrate the mechanism of chiral recognition. Based on the formation of an ionic liquid-boric acid-analyte complex, hydrogen binding was mainly responsible for enantioseparation.


Assuntos
Amino Álcoois/isolamento & purificação , Dissacarídeos/química , Líquidos Iônicos/química , Compostos de Amônio Quaternário/química , Amino Álcoois/química , Ácidos Bóricos/química , Dissacarídeos/síntese química , Eletroforese Capilar/métodos , Ligação de Hidrogênio , Líquidos Iônicos/síntese química , Modelos Moleculares , Compostos de Amônio Quaternário/síntese química , Estereoisomerismo , Trometamina/química
9.
Org Lett ; 21(21): 8736-8739, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625750

RESUMO

Asymmetric synthesis of γ-amino alcohols from unprotected allylic alcohols by a copper-catalyzed hydroamination strategy has been developed. Using easily accessible starting materials, a range of chiral 1,3-amino alcohols were prepared with excellent regio- and enantioselectivity. Further, this protocol provided an efficient one-step method for the enantioselective synthesis of γ-amino alcohols in an intermolecular manner.


Assuntos
Amino Álcoois/química , Amino Álcoois/síntese química , Cobre/química , Aminação , Catálise , Técnicas de Química Sintética
10.
J Am Chem Soc ; 141(41): 16382-16387, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31564090

RESUMO

The comprehensive determination of the absolute configuration, enantiomeric ratio, and total amount of standard amino acids by optical methods adaptable to high-throughput screening with modern plate readers has remained a major challenge to date. We now present a small-molecular probe that smoothly reacts with amino acids and biothiols in aqueous solution and thereby generates distinct chiroptical responses to accomplish this task. The achiral sensor is readily available, inexpensive, and suitable for chiroptical analysis of each of the 19 standard amino acids, biothiols, aliphatic, and aromatic amines and amino alcohols. The sensing method is operationally simple, and data collection and processing are straightforward. The utility and practicality of the assay are demonstrated with the accurate analysis of 10 aspartic acid samples covering a wide concentration range and largely varying enantiomeric compositions. Accurate er sensing of 85 scalemic samples of Pro, Met, Cys, Ala, methylpyrrolidine, 1-(2-naphthyl)amine, and mixtures thereof is also presented.


Assuntos
Aminas/química , Aminoácidos/química , Amino Álcoois/química , Fenômenos Ópticos , Compostos de Sulfidrila/química , Fluoretos , Estrutura Molecular
11.
Chemistry ; 25(53): 12303-12307, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31373735

RESUMO

Triplex forming oligonucleotides are used as a tool for gene regulation and in DNA nanotechnology. By incorporating artificial nucleic acids, target affinity and biological stability superior to that of natural DNA may be obtained. This work demonstrates how a chimeric clamp consisting of acyclic (L)-threoninol nucleic acid (aTNA) and DNA can bind DNA and RNA by the formation of a highly stable triplex structure. The (L)-aTNA clamp is released from the target again by the addition of a releasing strand in a strand displacement type of reaction. It is shown that the clamp efficiently inhibits Bsu and T7 RNA polymerase activity and that polymerase activity is reactivated by displacing the clamp. The clamp was successfully applied to the regulation of luciferase expression by reversible binding to the mRNA. When targeting a sequence in the double stranded plasmid, 40 % downregulation of protein expression is achieved.


Assuntos
RNA Polimerases Dirigidas por DNA/química , DNA/química , Ácidos Nucleicos/química , RNA/química , Proteínas Virais/química , Amino Álcoois/química , Butileno Glicóis/química , RNA Polimerases Dirigidas por DNA/metabolismo , RNA Polimerases Dirigidas por DNA/farmacologia , Proteínas Virais/metabolismo , Proteínas Virais/farmacologia
12.
Int J Mol Sci ; 20(16)2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430981

RESUMO

A library of isopulegol-based bi-, tri- and tetrafunctional chiral ligands has been developed from commercially available (-)-isopulegol and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. Michael addition of primary amines towards α-methylene-γ-butyrolactone, followed by reduction, was accomplished to provide aminodiols in highly stereoselective transformations. Stereoselective epoxidation of (+)-neoisopulegol, derived from natural (-)-isopulegol, and subsequent oxirane ring opening with primary amines afforded aminodiols. The regioselective ring closure of N-substituted aminodiols with formaldehyde was also investigated. Hydroxylation of (+)-neoisopulegol resulted in diol, which was then transformed into aminotriols by aminolysis of its epoxides. Dihydroxylation of (+)-neoisopulegol or derivatives with OsO4/NMO gave neoisopulegol-based di-, tri- and tetraols in highly stereoselective reactions. The antimicrobial activity of aminodiol and aminotriol derivatives as well as di-, tri- and tetraols was also explored. In addition, structure-activity relationships were examined by assessing substituent effects on the aminodiol and aminotriol systems.


Assuntos
Monoterpenos Cicloexânicos/síntese química , 4-Butirolactona/síntese química , 4-Butirolactona/química , Aminação , Amino Álcoois/síntese química , Amino Álcoois/química , Benzaldeídos/síntese química , Benzaldeídos/química , Catálise , Técnicas de Química Sintética , Monoterpenos Cicloexânicos/química , Ligantes , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Estereoisomerismo
13.
Org Biomol Chem ; 17(33): 7655-7659, 2019 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-31360984

RESUMO

Acyclic (l)-threoninol nucleic acids ((l)-aTNA) containing poly-cytosines are prepared and investigated at various pH values, revealing the formation of a highly stable structure at lower pH that have the characteristics of an i-motif. Depending on the sequence, the aTNA forms inter-, bi- and intra-molecular i-motif structures. Pyrene was conjugated to aTNA sequences and both monomeric and excimer fluorescence were efficiently quenched by the i-motif structures and thus demonstrated that the aTNA i-motif can serve as a pH switch.


Assuntos
Amino Álcoois/síntese química , Butileno Glicóis/síntese química , Ácidos Nucleicos/síntese química , Amino Álcoois/química , Butileno Glicóis/química , Concentração de Íons de Hidrogênio , Conformação Molecular , Ácidos Nucleicos/química , Poli C/química
14.
J Mol Model ; 25(8): 229, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31321557

RESUMO

Alzheimer's disease (AD) is a complex neurodegenerative disorder associated with the aggregation of the amyloid-beta peptide (Aß) into large oligomers and fibrils that damage healthy brain cells. The predominant peptide fragments in the plaques are mainly formed by the Aß1-40 and Aß1-42 peptides, albeit the eleven-residue Aß25-35 segment is largely used in biological studies because it retains the neurotoxic properties of the longer Aß peptides. Recent studies indicate that treatment with therapeutic steroid hormones reduces the progress of the disease in AD models. Particularly, treatment with 17ß-aminoestrogens (AEs) has shown a significant alleviation of the AD development by inhibiting oxidative stress and neuronal death. Yet, the mechanism by which the AE molecules exhibit their beneficial effects remains speculative. To shed light into the molecular mechanism of inhibition of the AD development by AEs, we investigated the possibility of direct interaction with the Aß25-35 peptide. First, we calculate various interacting electronic properties of three AE derivatives as follows: prolame, butolame, and pentolame by performing DFT calculations. To account for the polymorphic nature of the Aß aggregates, we considered four different Aß25-35 systems extracted from AD relevant fibril structures. From the calculation of different electron density properties, specific interacting loci were identified that guided the construction and optimization of various complexes. Interestingly, the results suggest a similar inhibitory mechanism based on the direct interaction between the AEs and the M35 residue that seems to be general and independent of the polymorphic properties of the Aß aggregates. Our analysis of the complex formation provides a structural framework for understanding the AE therapeutic properties in the molecular inhibitory mechanism of Aß aggregation.


Assuntos
Peptídeos beta-Amiloides/química , Estrogênios/farmacologia , Agregados Proteicos , Amino Álcoois/química , Amino Álcoois/farmacologia , Estrenos/química , Estrenos/farmacologia , Estrogênios/química , Modelos Moleculares , Agregados Proteicos/efeitos dos fármacos , Eletricidade Estática
15.
Molecules ; 24(14)2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31330911

RESUMO

A series of novel deoxycholic acid (DCA) derivatives containing aliphatic diamine and aminoalcohol or morpholine moieties at the C3 position were synthesized by 3,26-epoxide ring-opening reactions. These compounds were investigated for their cytotoxicity in four human tumor cell lines and murine macrophages and for inhibitory activity against macrophage-mediated NO synthesis in vitro. Obtained data revealed that: (i) all amine-containing substituents significantly increased the cytotoxicity of the novel compounds (IC502-10 = 1.0-36.0 µM) in comparison with DCA (IC50DCA ≥ 82.9 µM); (ii) aminoalcohol moieties were more preferable than diamine moieties due to the fact they imparted better selectivity for tumor cells of the novel derivatives; (iii) the susceptibility of tested cell lines to derivatives diminished in the following order: HuTu-80 (duodenal carcinoma) ≈ HepG2 (hepatocarcinoma) > KB-3-1 (cervical carcinoma) > RAW264.7 (macrophages) > A549 (lung carcinoma); (iv) compounds 8 and 9, bearing aminoethanol and aminopropanol moieties, respectively, exhibited high cytotoxic selectivity indexes (SIHuTu-80 = 7.9 and 8.3, respectively) and good drug-likeness parameters; (v) the novel compounds do not display anti-NO activity. Mechanistic study revealed that compound 9 induces ROS-dependent cell death by activation of intrinsic caspase-dependent apoptosis and cytodestructive autophagy in HuTu-80 cells and vitamin D receptor can be considered as its primary target.


Assuntos
Amino Álcoois/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacologia , Diaminas/química , Animais , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Ácido Desoxicólico/síntese química , Relação Dose-Resposta a Droga , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Relação Estrutura-Atividade
16.
Chembiochem ; 20(16): 2125-2132, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31095838

RESUMO

Trichogin is a natural peptide endowed with antimicrobial and antitumor activity. A member of the peptaibol family, trichogin possesses a C-terminal amino alcohol. In the past, this moiety was substituted for a methyl ester for synthetic purposes and it was observed that this apparently slight modification caused significant changes in the peptide bioactivity. With the aim of understanding the reasons behind such observations, a detailed spectroscopic study on a number of trichogin analogues has been performed. Herein, data obtained from synchrotron radiation circular dichroism, NMR spectroscopy, and fluorescence spectroscopy in organic solvents at cryogenic temperatures are compared with those independently acquired by means of EPR spectroscopy at 80 K. It is unambiguously revealed that the presence of a reversible, temperature-driven, screw-sense interconversion from a right- to left-handed helix is determined by the C-terminal capping moiety. Data demonstrate, for the first time, the key role of a C-terminal methyl ester in promoting peptide screw-sense inversion.


Assuntos
Peptaibols/química , Temperatura , Sequência de Aminoácidos , Amino Álcoois/química , Ácidos Carboxílicos/química , Ésteres/química , Conformação Proteica em alfa-Hélice , Relação Estrutura-Atividade
17.
Chem Commun (Camb) ; 55(44): 6297-6300, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31089587

RESUMO

Optical chirality sensing of unprotected amino acids, hydroxy acids, amino alcohols, amines and carboxylic acids based on a practical mix-and-measure protocol with readily available copper, iron, palladium, manganese, cerium or rhodium salts is demonstrated. The generation of strong cotton effects allows quantitative ee analysis of small sample amounts with high speed. In contrast to previously reported assays the use of chromophoric reporter ligands and the control of metal coordination kinetics and redox chemistry are not necessary which greatly simplifies the sensing procedure with the benefit of reduced waste production and cost.


Assuntos
Aminas/química , Aminoácidos/química , Amino Álcoois/química , Ácidos Carboxílicos/química , Hidroxiácidos/química , Metais/química , Sais/química , Ligantes , Estereoisomerismo
18.
J Chromatogr A ; 1601: 340-349, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31060783

RESUMO

In this study, three functionalized chiral ionic liquids (CILs) derived from l-valinol, l-prolinol and l-phenylalaninol, namely N,N,N-trimethyl-l-valinol-bis(trifluoromethanesulfon)imide ([TMLV]+[Tf2N]-, CIL1), N,N-dimethyl-l-prolinol-bis(trifluoromethanesulfon)imide ([DMLP]+[Tf2N]-, CIL2) and N,N,N-trimethyl-l-phenylalaninol-bis(trifluoromethanesulfon)imide ([TMLP]+[Tf2N]-, CIL3), were synthesized and subsequently utilized for enantiomeric separation in capillary electrophoresis (CE) with 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as chiral selector for the first time. Compared with traditional single HP-ß-CD separation system, the synergistic system exhibited substantially improved separations of six tested drugs. Using the CIL1/HP-ß-CD as a model system, the influence of crucial parameters including the type and proportion of organic modifier, CILs concentration, HP-ß-CD concentration and buffer pH was investigated in detail. Additionally, molecular modeling with AutoDock was applied to elucidate the enhanced enantioselectivity in the presence of CILs, which has certain guiding value in predicting the migration order of the enantiomers and studying the interactions important for the chiral recognition.


Assuntos
Amino Álcoois/química , Eletroforese Capilar/métodos , Líquidos Iônicos/síntese química , 2-Hidroxipropil-beta-Ciclodextrina/química , Concentração de Íons de Hidrogênio , Líquidos Iônicos/química , Estereoisomerismo
19.
Chem Pharm Bull (Tokyo) ; 67(4): 393-396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930443

RESUMO

In order to develop an efficient organocatalyst for the enantioselective N-H insertion reaction via carbene/carbenoid, the catalytic core of the cinchona alkaloids was investigated. According to our working hypothesis of an eight-membered ring transition state in the N-H insertion reaction, two pairs of enantiomers related to 2-amino-1-phenylethanol were investigated for their chiral inducing potential. Since both (1R,2S)-isomers gave the N-phenyl-1-phenylglycine derivative enriched in the R-form, while their enantiomers gave the S-form, the 2-amino-1-phenylethanol structure is concluded to be the catalytic core of the cinchona alkaloid in the enantioselective N-H insertion reaction via rhodium(II) carbenoid.


Assuntos
Amino Álcoois/química , Alcaloides de Cinchona/química , Álcoois Benzílicos/química , Catálise , Complexos de Coordenação/química , Hidrogênio/química , Nitrogênio/química , Ródio/química , Estereoisomerismo
20.
Molecules ; 24(8)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027303

RESUMO

In this paper, the microwave (MW)-assisted catalyst-free and mostly solvent-free Kabachnik-Fields reaction of amino alcohols, paraformaldehyde, and various >P(O)H reagents (dialkyl phosphites, ethyl phenyl-H-phosphinate, and secondary phosphine oxides) is reported. The synthesis of N-2-hydroxyethyl-α-aminophosphonate derivatives was optimized in respect of the temperature, the reaction time, and the molar ratio of the starting materials. A few by-products were also identified. N,N-Bis(phosphinoylmethyl)amines containing a hydroxyethyl group were also prepared by the double Kabachnik-Fields reaction of ethanolamine with an excess of paraformaldehyde and secondary phosphine oxides. The crystal structure of a 2-hydroxyethyl-α-aminophosphine oxide and a bis(phosphinoylmethyl)ethanolamine was studied by X-ray analysis.


Assuntos
Aminas/química , Amino Álcoois/química , Micro-Ondas , Difração de Raios X
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