RESUMO
This protocol describes a procedure for the synthesis of syn-beta-amino alpha-substituted aldehydes, versatile intermediates in synthetic organic chemistry, via asymmetric, direct, one-pot, three-component, cross-Mannich reaction of two different aldehydes. The reaction consists of two steps; one is the formation of imine by the reaction of aldehyde and p-anisidine in the presence of Pro, and the second step is the enantioselective addition reaction of enamine generated from the other aldehyde and Pro with the imine generated in the first step. As the aldehyde easily racemizes, gamma-amino alcohol was isolated and characterized after reduction. The yield and diastereo- and enantioselectivities are generally excellent. It will take approximately 26 h to complete the protocol: 0.5 h to set up the reaction, 20.5 h for the reaction and 5 h for the isolation and purification.
Assuntos
Aldeídos/síntese química , Amino Álcoois/isolamento & purificação , Técnicas de Química Analítica/métodos , Aldeídos/química , Aminas/química , Amino Álcoois/química , Compostos de Anilina/química , Bases de Mannich/química , Estrutura Molecular , Prolina/químicaRESUMO
Oligoamines (spermidine, dipropylenetriamine and propylenediamine) were covalently attached to acridine via a hexamethylene linker. These oligoamine-acridine conjugates were efficiently bound to gap sites in substrate DNA, and promoted the DNA hydrolysis by a homogeneous Ce(IV)/ethylenediamine-N,N,N',N'-tetraacetate (EDTA) complex at these sites. In contrast, the hydrolysis of the double-stranded portion in the DNA was little affected by these conjugates, although they were strongly bound thereto by the intercalation of their acridine moieties. As a result, the gap site was selectively and efficiently hydrolyzed by combining the Ce(IV)/EDTA complex with the oligoamine--acridine conjugate. Either the oligoamine or the acridine was only poorly active for the purpose, substantiating the essential role of cooperation between them. The promotion of gap-selective DNA hydrolysis by the conjugates has been ascribed to electrostatic stabilization of a negatively charged transition state by their positive charges.
Assuntos
Acridinas/química , Cério/farmacologia , DNA de Cadeia Simples/metabolismo , Ácido Edético/farmacologia , Poliaminas/química , Acridinas/metabolismo , Acridinas/farmacologia , Sequência de Bases , Sítios de Ligação , DNA/química , DNA de Cadeia Simples/química , DNA de Cadeia Simples/efeitos dos fármacos , Sinergismo Farmacológico , Hidrólise , Cinética , Substâncias Macromoleculares , Dados de Sequência Molecular , Propilaminas/química , Propilaminas/metabolismo , Propilaminas/farmacologia , Análise Espectral , Espermidina/análogos & derivados , Espermidina/química , Espermidina/metabolismo , Espermidina/farmacologia , Eletricidade EstáticaRESUMO
High pressure induced by water-freezing has been successfully applied to the direct catalytic asymmetric-three component List-Barbas-Mannich reaction, in which higher yield and better enantioselectivity can be realized than those from the reaction at room temperature under 0.1 MPa.
