RESUMO
New acenaphthylene-based dithienylethenes have been prepared. Surprisingly they did not show photochromism. However, they readily underwent a tandem addition of a nucleophile and an electrophile, leading to a small library of dearomatized colourless analogues, which, on the contrary, were endowed with photochromic activity. In the absence of the electrophile, the intermediate obtained by C-attack readily aromatizes to give, surprisingly, a final product of direct aromatic nucleophilic substitution, which was not photochromically active.
RESUMO
A small library of natural product-like compounds has been assembled by coupling an Ugi multicomponent reaction with two postcondensation transformations, carried out in one-pot fashion: a S(N)2' cyclization followed by an intramolecular Heck reaction.
Assuntos
Compostos Heterocíclicos/síntese química , Ciclização , Compostos Heterocíclicos/química , Espectroscopia de Ressonância Magnética , Modelos MolecularesRESUMO
The synthesis of phosphatidyl serine containing saturated fatty acids was thoroughly studied and optimized in order to establish a protocol amenable to large-scale synthesis. The key step was a one-pot multicomponent reaction involving an O-benzyl phosphorodiamidite, protected serine and diacylglycerol, followed by in situ oxidation of the resulting phosphite. In order to replace expensive and poorly stable tetrazole, a screening of substitutes was carried out and imidazolium chloride was selected as the best suited one.
Assuntos
Fosfatidilserinas/síntese química , Diglicerídeos/química , Imidazóis/química , Compostos Organofosforados/químicaRESUMO
A very short convergent synthesis of dihydrobenzoxazepinones, bearing four diverse diversity points, based on coupling the Ugi reaction with a Mitsunobu cyclization, was developed. These compounds are potential α-helix mimics, where three of the four appendages are expected to imitate the residues in i, i + 4 and i + 7 positions. A library of 22 compounds bearing lipophilic substituents, designed to interact with the hydrophobic cleft of anti-apoptotic protein Bcl-xL, was synthesized. Preliminary biochemical tests, based on competitive binding, have already been carried out.
Assuntos
Química Orgânica/métodos , Compostos Heterocíclicos com 3 Anéis/síntese química , Estrutura Secundária de Proteína , Álcoois/síntese química , Álcoois/química , Compostos Heterocíclicos com 3 Anéis/química , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Ácido Salicílico/síntese química , Ácido Salicílico/químicaRESUMO
Research progress is often promoted by unexpected results that open the way to new scenarios. In this communication, an unprecedented condensation of arylacetic acids and isocyanides and the unusual base-mediated rearrangement of the resulting products to give two novel classes of polysubstituted pyrrolones and pyrrolidinediones are reported.
RESUMO
beta-amino acids have been employed in the past as bifunctional building blocks in intramolecular Ugi multicomponent reactions to yield beta-lactam derivatives. By using 7-azabicyclo[2.2.1]heptane-2-carboxylic acid, a different outcome has been observed and rationalised. The final compounds are polyfunctionalised azabicyclic peptidomimetics, and further elaboration can be achieved exploiting an additional carboxylic group that is not involved in the multicomponent step.
Assuntos
Compostos Azabicíclicos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Acilação , Aminoácidos/química , Mimetismo Molecular , Estereoisomerismo , beta-Lactamas/químicaRESUMO
A short (2 steps) synthesis of diverse benzoxazinones by coupling the Ugi multicomponent reaction with an intramolecular Mitsunobu substitution is reported. The cyclization step proceeds via an unexpected cine substitution.
Assuntos
Benzoxazinas/síntese química , Benzoxazinas/química , Métodos , Modelos Químicos , Estrutura MolecularRESUMO
Lactenediynes are compounds characterized by the fusion of a beta-lactam with a cyclodeca-3-ene-1,5-diyne. In this work the most promising members of this family have been activated by attaching a carbalkoxy or a carbamoyl group to the azetidinone nitrogen, and conjugated to various DNA-complexing moieties, either acting by intercalation or through groove binding. These conjugated artificial enediynes have been demonstrated to possess in vitro ability to produce single and double strand cleavage of plasmid DNA. As potency and capacity to induce double cut, they rank among the best simple enediyne analogues ever prepared. A thorough investigation was carried out in order to develop the best suited linkers for assembling these conjugates.
Assuntos
DNA/química , DNA/genética , Enedi-Inos/síntese química , Enedi-Inos/farmacologia , Lactonas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Enedi-Inos/química , Humanos , Estrutura Molecular , Plasmídeos/química , Plasmídeos/genética , Relação Estrutura-AtividadeRESUMO
A 4-component Ugi reaction with a suitable isocyanide, followed by a novel secondary transformation involving a Pd(II)-mediated (R5 = H) or a Pd(0)-mediated (R5 = CO2Me) SN2' cyclization to give highly functionalized N-acyl-2-vinylpyrrolidines, is reported. The overall yields are usually good and in most cases the Pd(0)-catalyzed reaction gave the final product in almost quantitative yield.
Assuntos
Paládio/química , Pirrolidinas/química , Ciclização , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
Multicomponent reactions are a powerful tool in combinatorial chemistry and diversity-oriented synthesis for the assembly of collections of complex molecules in a highly straightforward and efficient manner. Additional advantages in terms of isolation and purification can be obtained by performing these condensations on a polymeric support or with the aid of solid-supported reagents, scavengers or catalysts. This review covers research published in this area during the last two years and provides a perspective of future directions.
Assuntos
Técnicas de Química Combinatória/métodos , Indústria Farmacêutica/métodos , Compostos Orgânicos/síntese química , Indústria Química/métodos , Desenho de Fármacos , Estrutura Molecular , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/químicaRESUMO
A short, two-step approach to the synthesis of diazepane or diazocane systems, based on a Ugi multicomponent reaction followed by a subsequent intramolecular SN2 reaction was studied. 1-sulfonyl tetrahydrobenzo[e]-1,4-diazepin-1-ones 1 were obtained in very high yield through a Ugi multicomponent reaction followed by Mitsunobu cyclization. On the other hand, aliphatic 1-sulfonyl 1,4-diazepan-5-ones 2 could be obtained employing different cyclization conditions (sulfuryl diimidazole). A similar approach toward diazocane rings using hydroxamates as nucleophiles was less successful, affording only O-cyclized adducts or unexpected side products. A mechanistic explanation of the observed outcomes is proposed.
Assuntos
Azepinas/síntese química , Benzazepinas/síntese química , Ciclização , Compostos Heterocíclicos/síntese químicaRESUMO
The synthesis of new conformationally biased cyclic pentapeptides, incorporating the RGD sequence, and built around a tetrahydroazoninone scaffold, is reported. They exhibit interesting activity towards integrin alphaVbeta3 and a remarkable selectivity in comparison with integrin alphaVbeta5.
Assuntos
Compostos Azo/síntese química , Integrinas/metabolismo , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Compostos Azo/farmacologia , Humanos , Integrina alfaVbeta3/metabolismo , Ligantes , Conformação Molecular , Oligopeptídeos , Receptores de Vitronectina/metabolismo , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
A novel synthetic application of asymmetrized tris(hydroxymethyl)methane (THYM), obtained in both enantiomeric forms in high e.e. via a chemoenzymatic procedure, is described. Starting from the common precursor , N- and O-containing 6-membered heterocycles have been prepared exploiting ring-closing metathesis as the key step. Possible elaborations of the double bond in and have been explored and, in the case of , conversion into the glycosidase inhibitor isofagomine has been achieved.
Assuntos
Compostos Heterocíclicos/química , Metano/análogos & derivados , Metano/química , Ciclização , Espectroscopia de Ressonância MagnéticaRESUMO
This paper describes the synthesis of a bicyclic beta-amino acid scaffold in both pure enantiomeric forms and its application as chiral auxiliary in an intramolecular version of the Ugi multicomponent reaction (U-5C-4CR) to prepare alpha-amino acid derivatives of both D- and L-series in a straightforward and very stereoselective manner. The mild conditions required for the Ugi condensation and for the removal of the chiral auxiliary make this method very attractive to prepare a wide range of differently structured N-alkylated and unalkylated amino acid derivatives.
Assuntos
Aminoácidos/síntese química , Compostos Bicíclicos com Pontes/síntese química , Aldeídos/química , Aminoácidos/química , Compostos Bicíclicos com Pontes/química , Estrutura Molecular , EstereoisomerismoRESUMO
A conformationally restricted cyclic pentapeptide, containing an unsaturated 9-membered lactam as a semi-rigid scaffold, was prepared in a very convergent manner, through tandem Ugi reaction/ring closing metathesis.
Assuntos
Peptídeos Cíclicos/síntese química , Cristalografia por Raios X , Ciclização , Modelos Moleculares , Peptídeos Cíclicos/química , Conformação Proteica , EstereoisomerismoRESUMO
The total synthesis of two diastereoisomeric simplified dynemicin analogues is reported. The key steps involved are: the regio- and diastereoselective functionalisation of an appropriate racemic quinoline precursor and the ring closure to give the 10-membered enediyne moiety through a Pd(0)-catalysed Stille reaction. After the successful conversion of one of these derivatives into a compound more readily activable under nearly physiological conditions, the activity against plasmid DNA was evaluated.
Assuntos
Antraquinonas/síntese química , DNA/química , Plasmídeos/metabolismo , Antraquinonas/química , Antibacterianos/síntese química , Antibacterianos/química , Enedi-Inos , Espectroscopia de Ressonância Magnética , Modelos Químicos , Quinolinas/química , EstereoisomerismoRESUMO
beta-Acylamino-alpha-hydroxyamides and beta-acylamino-alpha-oxoamides, compounds known to be potent protease inhibitors, can be conveniently prepared with a highly convergent strategy involving a Passerini multicomponent reaction between a N-protected alpha-aminoaldehyde, a carboxylic acid and an isocyanide. After N-deprotection and concomitant acyl migration the desired beta-acylamino-alpha-hydroxyamide moiety is obtained and can be further elaborated, for example via oxidation of the secondary alcohol group. In this paper we report the studies that have been carried out in order to transfer this synthetic methodology onto polystyrene resin, using a photocleavable linker and a N-Boc protecting strategy.