RESUMEN
A highly diastereoselective method for the synthesis of novel spiro-tetrahydroquinoline derivatives is reported here, using a one-pot reaction method. All compounds were characterized by 1H-nuclear magnetic resonance (NMR) and mass spectroscopy, and their stereo configurations were confirmed by X-ray analysis. These activities of these derivatives were then tested in human keratocyte cells. The responses of cells to treatment with selected compounds were studied using scratch analysis, and the compounds were tested in a mouse excision wound model. Three of the derivatives demonstrated significant wound-healing activities.
Asunto(s)
Queratinocitos/efectos de los fármacos , Quinolinas/química , Compuestos de Espiro/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Humanos , Queratinocitos/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Moleculares , Compuestos de Espiro/química , EstereoisomerismoRESUMEN
An efficient and attractive synthesis of a series of novel poly-functionalized phosphorus zwitterions was achieved via three-component reactions of the corresponding functional nucleophiles, aldehydes, and Bu(3)P in the presence of acidic promoter. These polysubstituted zwitterions could regioselectively undergo further transformations to synthetically important furanonaphthoquinones and related products via the intramolecular Wittig reaction. These methods could have potential application in synthetic and pharmaceutical chemistry for its facilitation and easily accessible commercial materials.
Asunto(s)
Furanos/síntesis química , Naftoquinonas/síntesis química , Furanos/química , Iones/química , Naftoquinonas/química , Fósforo/química , EstereoisomerismoRESUMEN
A new and general strategy for highly functional furo[3,4-c]coumarins and related furyl coumarin derivatives has been developed, which is based on an extraordinarily facile intramolecular Wittig reaction, starting from α,ß-unsaturated ketones, tributylphosphine, and acyl chlorides. The phosphorus ylides were proposed to be the key intermediates for constructing the crucial furan ring, leading to a wide variety of substituted furyl coumarins in one step.
Asunto(s)
Técnicas de Química Sintética/métodos , Furanos/síntesis química , Furocumarinas/síntesis química , Fármacos Fotosensibilizantes/síntesis química , Técnicas de Química Sintética/economía , Cloruros/química , Furanos/química , Furocumarinas/química , Cetonas/química , Fosfinas/química , Fármacos Fotosensibilizantes/químicaRESUMEN
Organocatalysts bearing sulfide or sulfone functions (1a-d) were studied for the direct asymmetric Michael addition of ketones and alkylidene malonates. The organocatalyst (S)-2-((naphthalen-2-ylthio)methyl)pyrrolidine, bearing a pyrrolidine and a sulfide moiety, showed a very high catalytic activity in the absence of additives. The reaction condition is mild, and the Michael adducts were obtained in very good enantioselectivities (up to 96%), diastereoselectivities (up to 95:5), and chemical yields (up to 95%).
Asunto(s)
Cetonas/química , Malonatos/química , Pirrolidinas/química , Sulfuros/química , Catálisis , Estereoisomerismo , Especificidad por SustratoRESUMEN
A new highly efficient three-component reaction of alkyl acrylate, aldehyde and dialkyl malonate using ethyl diphenylphosphine as organocatalyst has been described. Various highly functional compounds bearing hydroxyl groups and the ester functions can be easily prepared in moderate to good yields according to our one-step procedure. The reactions are believed to proceed via Morita-Baylis-Hillman reactions of alkyl acrylate and aldehydes, followed by the Michael addition reactions of dialkyl malonates. Our reactions indicated that the intermediate species formed in the phosphine-catalyzed MBH reaction are an effective organic base to catalyze the Michael addition reactions of dialkyl malonates to the preformed MBH adducts.
Asunto(s)
Acrilatos/química , Aldehídos/química , Malonatos/química , Fosfinas/química , Catálisis , Estructura Molecular , EstereoisomerismoRESUMEN
A highly chemoselective PPh(3)-catalyzed three-component reaction of an imine, alkyl vinyl ketone, and phthalimide or succinimide is developed. Various highly functional adducts with high diastereoselectivities can be generated via aza-Morita-Baylis-Hillman reactions of aryl-substituted imines and alkyl vinyl ketones followed by Michael additions of imides and then epimerization.
RESUMEN
An efficient and mild synthesis of trisubstituted furans, starting from α,ß-unsaturated ketones, tributylphosphine, and acyl chlorides, is described. The strategy employs the intramolecular Wittig protocol as a key step to install the crucial furan ring, leading to a wide variety of highly functional furans in one step.
RESUMEN
Diterpenoids jolkinolide A and B, were first isolated from Euphorbia fischeriana. In our previous research, 19-(Benzyloxy)-19-oxojolkinolide B (19-BJB), a derivative of jolkinolides, was synthesized as a novel ent -abietane diterpene diepoxide. In this study, 19-BJB showed strong in vitro activity against bladder cancer cell lines. DNA damage which was observed through the interaction of 19-BJB with nucleotide chains and affected DNA repair resulted in the activation of checkpoint kinase 1 (Chk1) and checkpoint kinase 2 (Chk2) in bladder cancer cell lines. In vivo testing in nude mice also proved that 19-BJB revealed a potential inhibitory effect on tumor growth. Additionally, the 3D-QSAR models of jolkinolides were established. Briefly, we proved that 19-BJB could potentially be used as a drug to inhibit the growth of bladder tumor.
Asunto(s)
Abietanos/farmacología , Daño del ADN/efectos de los fármacos , Diterpenos/farmacología , Medicamentos Herbarios Chinos/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Abietanos/uso terapéutico , Animales , Antineoplásicos Fitogénicos , Línea Celular Tumoral , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/metabolismo , Quinasa de Punto de Control 2/metabolismo , Reparación del ADN , Diterpenos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Euphorbia/química , Humanos , Masculino , Ratones , Simulación del Acoplamiento Molecular , Neoplasias de la Vejiga Urinaria/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
An efficient synthesis of functionalized benzofurans is achieved under mild and metal-free conditions from stable para-quinone methides by treatment with phosphine, acyl chloride, and a base. This one-pot phospha-1,6-addition/O-acylation/Wittig reaction is also demonstrated under catalytic conditions with similar efficacy.
RESUMEN
An efficient organocatalytic quadruple cascade reaction resulting in spiroxindole scaffolds bearing five quaternary stereocenters is reported. The complex cascade reaction is triggered by the scarcely explored vinylogous Michael addition of 3-alkylidene oxindoles to fully substituted enones and demonstrates the usefulness of the latter as efficient Michael acceptors in generating complex caged products in 26-92% yields, 14-98% ee and up to >25 : 1 d.r. values.
RESUMEN
A general preparation of new types of highly functional phosphorus zwitterions is realized via tandem three-component reactions using the corresponding functional alkanes, aldehydes, and Bu(3)P. Starting from our novel zwitterions as synthetic reagents with commercially available acid chlorides in a one-step procedure provides an attractive approach toward furo[3,2-c]coumarins.
RESUMEN
A general preparation of new types of benzofurans, benzothiophenes and indoles is realized via chemoselective intramolecular Wittig reactions with the corresponding ester, thioester and amide functionalities using in situ formed phosphorus ylides as key intermediates. The reaction conditions are very mild, and numerous Michael acceptors and commercially available acid chlorides can be applied very efficiently in a one-step procedure.
Asunto(s)
Benzofuranos/síntesis química , Indoles/síntesis química , Tiofenos/síntesis química , Amidas/síntesis química , Amidas/química , Benzofuranos/química , Cloruros/síntesis química , Cloruros/química , Ésteres/síntesis química , Ésteres/química , Indoles/química , Compuestos Organofosforados/síntesis química , Compuestos Organofosforados/química , Tiofenos/químicaRESUMEN
Preparation of new types of highly functional benzofurans, benzothiophenes, and indoles is realized via intramolecular Wittig reactions with the corresponding ester, thioester, and amide functionalities. The key intermediates, phosphorus ylides, presumably result from the addition of Bu(3)P toward aldehydes followed by acylation and deprotonation. Synthesis of functional benzofurans directly starting from salicylic aldehyde derivatives with acid chlorides in a one-step procedure is also developed.
Asunto(s)
Amidas/química , Derivados del Benceno/síntesis química , Benzofuranos/síntesis química , Indoles/síntesis química , Tiofenos/síntesis química , Aldehídos/síntesis química , Derivados del Benceno/química , Benzofuranos/química , Ésteres , Indoles/química , Estructura Molecular , Tiofenos/químicaRESUMEN
Various geometrically pure (E)-beta-alkyl-styrenes have been synthesized by the radical NO(2) substitution of alkyl moieties generated via hydrogen abstraction followed by decarbonylation from aliphatic aldehydes. These reactions, which involve a high chemical selectivity and regioselectivity constitute a new route to (E)-beta-alkylstyrenes. Both aliphatic and aromatic aldehydes can be used in this novel reaction. When 2-allyloxybenzaldehyde was used, the benzoyl radical added directly to the double bond without decarbonylation to give the 3-cinnamylchroman-4-one. This unique difference between aliphatic and aromatic aldehydes represents a simple route for the synthesis of biologically important chromanones.
RESUMEN
Stereoselective styryl derivatives have been prepared based on radical substitution (addition-elimination) of heterocycles or cyclohydrocarbons units to (E)-beta-nitrostyrenes 1 using a common radical initiator benzoyl peroxide. High reactivity and selectivity with wide substrate scope were attained by using this easy methodology. The reactions using easily obtained and one-pot potential starting materials gave excellent trans-selectivity with medium to high yields in all cases. Synthetic utility of this approach has been demonstrated by the preparation of various trans-styryl derivatives.