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.
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 , EstereoisomerismoRESUMO
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/químicaRESUMO
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/urinaRESUMO
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 , EstereoisomerismoRESUMO
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.
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.
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 MolecularRESUMO
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 MolecularRESUMO
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 , EstereoisomerismoRESUMO
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/químicaRESUMO
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 MolecularRESUMO
Chiral cyclobutanone which had ethyl l-lactate as a chiral auxiliary at the 3-position reacted with aldehydes to give 2,3-dihydro-4-pyranones in up to 93% ee by combined use of titanium(IV) chloride and tin(II) chloride.
Assuntos
Aldeídos/química , Ciclobutanos/química , Hidrogênio/química , Piranos/síntese química , Catálise , Ciclização , Estrutura Molecular , EstereoisomerismoRESUMO
Treatment of 3,3-dialkylcyclobutanones with titanium(IV) chloride in the presence of aldehyde gave beta'-chloro-beta-hydroxy ketones in high yields. It was speculated that ring cleavage of the cyclobutanone ring with titanium(IV) chloride gave trichlorotitanium enolate having a tertiary alkyl chloride moiety and then aldol reaction of the titanium enolate proceeded. A trialkylsilylmethyl group at the 2-position of cyclobutanone facilitated the ring cleavage. Synthesis of substituted cyclopentenone from an obtained product is also described.
Assuntos
Aldeídos/química , Ciclobutanos/química , Ciclopentanos/síntese química , Hidrocarbonetos Clorados/síntese química , Cetonas/química , Cetonas/síntese química , Compostos de Organossilício/química , Titânio/química , Técnicas de Química Combinatória , Ciclopentanos/química , Hidrocarbonetos Clorados/química , Estrutura MolecularRESUMO
N-p-Toluenesulfonyl (Ts) aldimines reacted with 3-ethoxycyclobutanones by catalysis of titanium(IV) chloride to afford 2,3-di- or 2,3,3-trisubstituted N-Ts-2,3-dihydro-4-pyridones. Synthesis of (+/-)-bremazocine was efficiently accomplished by using this method.
Assuntos
Benzomorfanos/química , Benzomorfanos/síntese química , Ciclobutanos/química , Iminas/química , Piridonas/química , Piridonas/síntese química , Titânio/química , Catálise , EstereoisomerismoRESUMO
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 , CiclizaçãoRESUMO
Ketones and acyl silanes were reduced to the corresponding alcohols by a simple procedure employing anti-1,3-diol and a catalytic amount (5 mol %) of 2,4-dinitrobenzenesulfonic acid in benzene at reflux. Asymmetric induction reached up to >99% ee when a chiral pentane-2,4-diol of 97% ee was used.
Assuntos
Álcoois/síntese química , Benzenossulfonatos/química , Glicóis/química , Cetonas/química , Silanos/química , Álcoois/química , Catálise , Estrutura Molecular , Oxirredução , EstereoisomerismoRESUMO
Efficient catalytic and stereoselective glycosylation was achieved by activating a glycosyl N-trichloroacetylcarbamate with a catalytic amount of Lewis acid in the presence of a glycosyl acceptor and 5A molecular sieves. Catalytic one-pot dehydrative glycosylation of a 1-hydroxy carbohydrate was achieved stereoselectively by reaction with trichloroacetyl isocyanate, followed by activation with a catalytic amount of activators.
Assuntos
Carbamatos/química , Carboidratos/química , Catálise , Glicosilação , Espectroscopia de Ressonância Magnética , Modelos Químicos , Estrutura Molecular , EstereoisomerismoRESUMO
Intramolecular formal [4+2] cycloaddition between 3-ethoxycyclobutanones and a carbon-carbon double bond to the corresponding bicyclo[4.n.0]alkan-2-one derivatives proceeded effectively by using ethylaluminium dichloride.