RESUMO
A rapid and atom economical multicomponent synthesis of complex aza-diketopiperazines (aza-DKPs) driven by Rh(i)-catalyzed hydroformylation of alkenylsemicarbazides is described. Combined with catalytic amounts of acid and the presence of nucleophilic species, this unprecedented multicomponent reaction (MCR) enabled the formation of six bonds and a controlled stereocenter from simple substrates. The efficacy of the strategy was demonstrated with a series of various allyl-substituted semicarbazides and nucleophiles leading to the preparation of 3D-shaped bicyclic aza-DKPs. Moreover, an analysis of their 3D molecular descriptors and "drug-likeness" properties highlights not only their originality in the chemical space of aza-heterocycles but also their great potential for medicinal chemistry.
Assuntos
Compostos Aza/síntese química , Dicetopiperazinas/síntese química , Compostos Aza/química , Catálise , Técnicas de Química Combinatória/métodos , Dicetopiperazinas/química , Ródio/química , Semicarbazidas/síntese química , Semicarbazidas/química , EstereoisomerismoRESUMO
Trimethylsilyl-transient protection successfully allowed the use of lithium hexamethyldisilazane to prepare benzimidazole (BI) and 4-azabenzimidazole (azaBI) amidines from nitriles in 58-88% yields. This strategy offers a much better choice to prepare BI/azaBI amidines than the lengthy, low-yielding Pinner reaction. Synthesis of aza/benzimidazole rings from aromatic diamines and aldehydes was affected in dimethyl sulfoxide in 10-15 min, while known procedures require long time and purification. These methods are important for the BI/azaBI-based drug industry and for developing specific DNA binders for expanded therapeutic applications.
Assuntos
Amidinas/síntese química , Compostos Aza/química , Benzimidazóis/química , Imidazóis/síntese química , Compostos de Lítio/química , Nitrilas/química , Silanos/química , Amidinas/química , Compostos Aza/síntese química , Benzimidazóis/síntese química , Dimetil Sulfóxido/química , Imidazóis/química , Estrutura Molecular , Nitrilas/síntese químicaRESUMO
The first water soluble maleimide bearing NIR BF2-azadipyrromethene (NIR-AZA) fluorochrome has been synthesised which is capable of rapid thiol conjugations in water with peptides such as glutathione, the cell penetrating peptide (CPP) C(ß-A)SKKKKTKV-NH2 and a thiol substituted cRGD. NIR fluorescence imaging showed rapid cellular delivery of the CPP conjugate and effective in vivo tumour localization for the cRGD conjugate.
Assuntos
Compostos Aza/síntese química , Corantes Fluorescentes/síntese química , Raios Infravermelhos , Maleimidas/química , Porfobilinogênio/análogos & derivados , Animais , Compostos Aza/química , Compostos Aza/farmacocinética , Fluorescência , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Glutationa/química , Glutationa/farmacocinética , Células HeLa , Humanos , Maleimidas/farmacocinética , Camundongos , Estrutura Molecular , Neoplasias Experimentais/metabolismo , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacocinética , Porfobilinogênio/química , Porfobilinogênio/farmacocinética , Compostos de Sulfidrila/químicaRESUMO
A wide variety of functionalized 2-aryl benzimidazoles can be prepared by a solvent-free cobalt- or iron-catalyzed redox condensation of 2-nitroanilines and benzylamines. The cascade including benzylamine oxidation, nitro reduction, condensation, and aromatization occurs without any added reducing or oxidizing agent. The method can be extended to other alkylamines as reducing components or 2-nitrobenzamides as oxidizing components when using an iron/sulfur catalyst to afford various diazaheterocycles.
Assuntos
Aminas/química , Compostos Aza/síntese química , Cobalto/química , Compostos Heterocíclicos/síntese química , Ferro/química , Nitrobenzenos/química , Compostos Aza/química , Catálise , Compostos Heterocíclicos/química , Estrutura Molecular , OxirreduçãoRESUMO
Uncatalysed 1,3-dipolar cycloaddition reactions between two phosphaalkynes, P≡CR (R = Bu(t) or Me), and a series of di-, tri- and poly-azido precursor compounds have given very high yields of a range of triazaphosphole substituted systems. These comprise the 1,1'-bis(triazaphosphole)ferrocenes, [Fe{C5H4(N3PCR)}2], the tris(triazaphosphole)cyclohexane, cis-1,3,5-C6H9(N3PCBu(t))3, and the poly(allyltriazaphosphole)s, {C3H5(N3PCR)}∞. Electrochemical studies on the 1,1'-bis(triazaphosphole)ferrocenes reveal the compounds to undergo reversible 1-electron oxidation processes, at significantly more positive potentials than ferrocene itself. Attempts to chemically oxidise one 1,1'-bis(triazaphosphole)ferrocene with a silver salt, Ag[Al{OC(CF3)3}4] were not successful, and led to the formation of a silver coordination complex, [{Fe[µ-C5H4(N3PCBu(t))]2(µ-Ag)}2][Al{OC(CF3)3}4]2, thereby demonstrating the potential the reported triazaphosphole substituted systems possess as novel ligands in coordination chemistry.
Assuntos
Compostos Aza/química , Química Click/métodos , Cicloexanos/química , Compostos Ferrosos/química , Compostos Aza/síntese química , Química Click/economia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cristalografia por Raios X , Reação de Cicloadição/economia , Reação de Cicloadição/métodos , Cicloexanos/síntese química , Técnicas Eletroquímicas , Compostos Ferrosos/síntese química , Metalocenos , Modelos Moleculares , Oxirredução , Prata/químicaRESUMO
[reaction: see text] An expedient, atom-economical, asymmetric synthesis of 1-aryl-3-azabicyclo[3.1.0]hexanes, including (+)-Bicifadine and DOV21947, in a single-stage through process without isolation of any intermediates has been developed. The key of this synthesis is the in-depth mechanistic understanding of the complicated epoxy nitrile coupling at each reaction stage. Therefore, the desired trisubstituted cyclopropane can be prepared in high ee and yield by controlling the reaction pathway through manipulating the nitrile anion aggregation state.