Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
1.
Neurochem Res ; 45(11): 2664-2678, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32844295

RESUMO

Understanding of the underlying mechanism of epilepsy is desired since some patients fail to control their seizures. The carnitine/organic cation transporter OCTN1/SLC22A4 is expressed in brain neurons and transports food-derived antioxidant ergothioneine (ERGO), L-carnitine, and spermine, all of which may be associated with epilepsy. This study aimed to clarify the possible association of this transporter with epileptic seizures. In both pentylenetetrazole (PTZ)-induced acute seizure and kindling models, ocnt1 gene knockout mice (octn1-/-) showed lower seizure scores compared with wild-type mice. Up-regulation of the epilepsy-related genes, c-fos and Arc, and the neurotrophic factor BDNF following PTZ administration was observed in the hippocampus of wild-type, but not octn1-/- mice. To find the OCTN1 substrate associated with the seizure, untargeted metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry was conducted on extracts from the hippocampus, frontal cortex, and plasma of both strains, leading to the identification of a plant alkaloid homostachydrine as a compound present in a lower concentration in octn1-/- mice. OCTN1-mediated uptake of deuterium-labeled homostachydrine was confirmed in OCTN1-transfected HEK293 cells, suggesting that this compound is a substrate of OCTN1. Homostachydrine administration increased PTZ-induced acute seizure scores and the expression of Arc in the hippocampus and that of Arc, Egr1, and BDNF in the frontal cortex. Conversely, administration of the OCTN1 substrate/inhibitor ERGO inhibited PTZ-induced kindling and reduced the plasma homostachydrine concentration. Thus, these results suggest that OCTN1 is at least partially associated with PTZ-induced seizures, which is potentially deteriorated by treatment with homostachydrine, a newly identified food-derived OCTN1 substrate.


Assuntos
Epilepsia/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Piperidinas/farmacologia , Convulsões/metabolismo , Simportadores/metabolismo , Xenobióticos/farmacologia , Animais , Antioxidantes/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas do Citoesqueleto/metabolismo , Epilepsia/induzido quimicamente , Ergotioneína/farmacologia , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Pentilenotetrazol , Piperidinas/metabolismo , Piperidinas/urina , Convulsões/induzido quimicamente , Simportadores/genética , Xenobióticos/metabolismo , Xenobióticos/urina
2.
Chem Pharm Bull (Tokyo) ; 68(12): 1201-1209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33268652

RESUMO

Regioselectivity for intramolecular Diels-Alder (IMDA) reactions of 6-acetoxy-6-alkenylcyclohexa-2,4-dien-1-ones that were formed by oxidation of 2-alkenylphenols with lead tetraacetate in acetic acid were studied. Bridged regioselectivity was observed in the IMDA reactions of 6-acetoxy-6-alkenylcyclohexa-2,4-dien-1-ones having a dienophile part which could conjugate with an aromatic group. Bridged seven- and eight-membered rings and bicyclo[2.2.2]octane skeletons were constructed by the present IMDA reactions. Density functional theory (DFT) calculations suggested that conjugation of the dienophile with neighboring aromatic groups lowered the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap and preceded bridged [4 + 2] adducts.


Assuntos
Compostos Bicíclicos com Pontes/síntese química , Octanos/síntese química , Compostos Bicíclicos com Pontes/química , Reação de Cicloadição , Teoria da Densidade Funcional , Estrutura Molecular , Octanos/química , Estereoisomerismo
3.
Chem Pharm Bull (Tokyo) ; 68(12): 1220-1225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33268654

RESUMO

The nitrolactonization of alkenyl carboxylic acids mediated by Fe(NO3)3·9H2O has been developed. Nitrolactones were obtained in up to 93% yield by treatment of alkenyl carboxylic acids with Fe(NO3)3·9H2O. Mechanistic studies disclosed that the reaction proceeded through a radical intermediate generated from addition of NO2 to alkenyl carboxylic acids.


Assuntos
Ácidos Carboxílicos/química , Desenvolvimento de Medicamentos , Compostos Férricos/química , Nitratos/química , Nitrocompostos/síntese química , Estrutura Molecular , Nitrocompostos/química , Água/química
4.
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
5.
Org Biomol Chem ; 15(25): 5268-5271, 2017 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-28613322

RESUMO

Nucleophilic alkynes bearing sulfonamide, trimethylsilyl, or p-methoxyphenyl groups at the sp carbon reacted with 3-ethoxycyclobutanones to give formal [4 + 2] cycloadducts by activation with TiCl4. Reactions with 2-monoalkyl and 2-nonsubstituted 3-ethoxycyclobutanones gave phenol derivatives directly by benzannulation, while the use of 2,2-dimethyl-3-ethoxycyclobutanone gave the corresponding dienones, which were converted to pentasubstituted phenols by dienone-phenol rearrangement. Regioselectivity that depended on the activation conditions of dienone-phenol rearrangement is also described.

6.
Angew Chem Int Ed Engl ; 52(35): 9109-18, 2013 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-23881865

RESUMO

A directed cross-aldol reaction of silyl enol ethers with carbonyl compounds, such as aldehydes and ketones, promoted by a Lewis acid, a reaction which is now widely known as the Mukaiyama aldol reaction. It was first reported in 1973, and this year marks the 40th anniversary. The directed cross-aldol reactions mediated by boron enolates and tin(II) enolates also emerged from the Mukaiyama laboratory. These directed cross-aldol reactions have become invaluable tools for the construction of stereochemically complex molecules from two carbonyl compounds. This Minireview provides a succinct historical overview of their discoveries and the early stages of their development.


Assuntos
Aldeídos/síntese química , Aldeídos/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Estrutura Molecular
7.
Org Lett ; 25(49): 8952-8956, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38055630

RESUMO

An asymmetric synthesis via an axially chiral arylaryne intermediate was developed. A cycloaddition reaction with various arynophiles was used to obtain chiral biaryl compounds while preserving the enantiomeric excess (ee) of a precursor even though the reaction proceeds through an arylaryne intermediate, whose ee decreases on a time-dependent basis. High chiral transfer from a precursor to a product was observed not only at low temperature (-78 °C) but also at room temperature.

8.
Chem Pharm Bull (Tokyo) ; 60(1): 21-2, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22223370

RESUMO

A catalytic amount of tin(IV) chloride catalyzed formal [4+2] cycloaddition reaction of di-tert-butyl 2-ethoxycyclobutane-1,1-carboxylate with ketones or aldehydes to give diethyl 6-ethoxydihydro-2H-pyran-3,3(4H)-dicarboxylates, whereas two equivalents of trimethylsilyl triflate promoted tandem [4+2] cycloaddition and lactonization to afford 3-oxo-2,6-dioxabicyclo[2.2.2]octane-4-carboxylate esters.


Assuntos
Aldeídos/química , Ácidos Dicarboxílicos/química , Cetonas/química , Catálise , Ciclização , Ácidos Dicarboxílicos/síntese química , Lactonas/química , Compostos de Estanho/química
9.
Chem Pharm Bull (Tokyo) ; 60(6): 793-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22689434

RESUMO

ß'-Chloro and ß',γ'-unsaturated trichlorotitanium enolates, which were formed in situ by titanium(IV) chloride-mediated ring cleavage of 3,3-dialkylcyclobutanones and 3-[(trimethylsilyl)methyl]cyclobutanones, reacted with enones to give Michael adducts with keeping a labile ß'-chloro or ß',γ'-unsaturated group.


Assuntos
Butanonas/química , Cloretos/química , Titânio/química , Compostos de Trimetilsilil/química , Ciclização , Cetonas/síntese química , Cetonas/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular
10.
Chem Pharm Bull (Tokyo) ; 60(4): 548-53, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22466740

RESUMO

Intramolecular [2+2] cycloaddition of γ,δ-unsaturated ketenes derived from hex-5-enoyl chloride derivatives gave bicyclo[2.1.1]hexan-5-ones with complete regioselectivity.


Assuntos
Compostos Bicíclicos com Pontes/química , Etilenos/química , Cetonas/química , Metil n-Butil Cetona/química , Ciclização , Etilenos/síntese química , Cetonas/síntese química , Estereoisomerismo
11.
Chem Pharm Bull (Tokyo) ; 58(4): 591-2, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20410651

RESUMO

Trialkylamine-mediated intramolecular cyclization of pent-4-enoyl chlorides was studied. Substitution with a tertiary alkyl group at the 2-position gave cyclopent-2-en-1-ones, while substitution with an aromatic group gave enol esters, which were formed by O-acylation of initially formed 3-chlorocyclopentanones with ketenes.


Assuntos
Alcenos/química , Ácidos Carboxílicos/química , Cloretos/química , Etilenos/química , Cetonas/química , Acilação , Ciclização
12.
J Am Chem Soc ; 130(35): 11600-1, 2008 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-18693726

RESUMO

Intermolecular [4 + 2] cycloaddition between 3-alkoxycyclobutanones and aldehydes or ketones by the activation with boron trifluoride etherate is reported. The carbonyl compounds are inserted into the less substituted C2-C3 bond of the cyclobutanone ring of 6-alkyl-2-oxabicyclo[4.2.0]octan-7-ones to afford 1-alkyl-5,7-dioxabicyclo[4.4.0]decan-2-one derivatives regioselectively (>99:1) and diastereoselectively. On the other hand, [4 + 2] cycloaddition of 3-ethoxy-2,2-dialkylcyclobutanones at low temperature proceeds at the more substituted C2-C3 bond to yield 3,3-dialkyl-6-ethoxy-2,3,5,6-tetrahydro-4H-pyran-4-one derivatives with high regioselectivities. This [4 + 2] cycloaddition is developed into a one-pot synthesis of tri- or tetrasubstituted dihydro-gamma-pyrones from 3-ethoxycyclobutanones which are readily prepared from acid chloride and ethyl vinyl ether. The two regioselectivities observed in ring-opening of cyclobutanones can ascribe to thermodynamic stabilities of zwitterionic intermediates generated from tetrahydropyran-fused cyclobutanones and 3-ethoxycyclobutanones.


Assuntos
Aldeídos/química , Ciclobutanos/química , Cetonas/química , Boranos/química , Compostos Bicíclicos com Pontes/síntese química , Compostos Bicíclicos com Pontes/química , Catálise , Ciclização , Ciclo-Octanos/química , Mesilatos/química , Compostos de Trimetilsilil/química
13.
J Org Chem ; 73(17): 6902-4, 2008 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-18683979

RESUMO

Oxazaborolidine-catalyzed enantioselective reduction of alpha-methylene ketones was efficiently carried out by using borane-diethylaniline as a stoichiometric reducing agent. The combination of this method and subsequent hydrogenation of thus-formed allylic alcohol improved stereoselectivity in the reduction of 24-oxocholesteryl ester to 24-(R)-hydroxycholesteryl ester.


Assuntos
Compostos Aza/química , Compostos de Boro/química , Cetonas/química , Propanóis/síntese química , Compostos de Anilina/química , Boranos/química , Catálise , Ésteres do Colesterol/química , Hidrogenação , Modelos Químicos , Oxirredução , Estereoisomerismo
15.
Org Lett ; 8(26): 6095-8, 2006 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-17165938

RESUMO

[Structure: see text] Various alkenes were prepared from phenyl sulfides in a one-pot manner at room temperature by converting them to the corresponding S-aminosulfonium salts with O-mesitylenesulfonylhydroxylamine, followed by treatment with potassium carbonate. Alkenes were formed by cis-elimination of in situ generated phenyl sulfilimines.


Assuntos
Alcenos/química , Iminas/química , Sulfetos/química , Temperatura
16.
Org Lett ; 8(19): 4371-4, 2006 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-16956229

RESUMO

Efficient carbon-carbon bond formation at the alpha-position of nitrogen was established by one-pot oxidative Mannich reaction of N-carbobenzyloxy (Cbz) amines with 1,3-dicarbonyl compounds using N-tert-butylbenzenesulfinimidoyl chloride as an oxidant.


Assuntos
Aminas/química , Cetonas/química , Oxirredução
17.
Chem Commun (Camb) ; (27): 2896-8, 2006 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-17007409

RESUMO

N-Carbobenzyloxy (Cbz) ketimines were prepared conveniently from N-Cbz amines by oxidation with N-tert-butylbenzenesulfinimidoyl chloride.


Assuntos
Iminas/síntese química
18.
Org Lett ; 18(19): 4951-4953, 2016 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-27648942

RESUMO

α-Chloro- or α-bromo-γ-hydroxyenamides were synthesized by the reaction of an ynamide, titanium tetrahalide, and an aldehyde or a ketone. A γ-hydroxy trisubstituted enamide was prepared stereoselectively by Suzuki coupling of an obtained α-chloro-γ-hydroxyenamide with phenyl boronic acid. Intramolecular cyclization of α-chloro-γ-hydroxyenamide took place to provide a 2,3-dihydrobenzoisothiazole 1,1-dioxide derivative by palladium-catalyzed C-H activation of the tosyl group. Hydrochlorination of ynamides proceeded to give α-chloroenamides by treatment with titanium tetrachloride followed by addition of water.

19.
Chem Commun (Camb) ; (18): 2399-401, 2005 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-15877141

RESUMO

Vinylic hydrogens at the beta-position of enones were effectively substituted with alkyl groups in a one-pot procedure to afford beta-alkyl enones in good to high isolated yields by conjugate addition of higher-order dialkyl cyanocuprates to enones, followed by a reaction with N-tert-butylbenzenesulfinimidoyl chloride at -78 degree C.

20.
Org Lett ; 13(22): 5986-9, 2011 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-22007918

RESUMO

3-[(Trialkylsilyl)methyl]cyclobutanones reacted with aldehydes by activation with titanium(IV) chloride to give acyclic ß,γ-unsaturated ß'-hydroxyketones.


Assuntos
Ciclobutanos/química , Aldeídos/química , Alquilação , Metilação , Estrutura Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA