RESUMO
The dimeric natural product montamine was originally reported as two N-feruloylserotonin (moschamine) units linked by a nitrogen-nitrogen bond, but our recent synthesis of this symmetrical diacyl hydrazide structure revealed this to be incorrect. We subsequently hypothesized that the moschamine subunits were linked through the indole C4 site and that montamine was structurally identical to 4,4'-bismoschamine, a known natural product present in safflower oil. However, given that authentic samples of both montamine and 4,4'-bismoschamine were unavailable and that the NMR data for the natural products were recorded in different solvents, we were unable to unequivocally prove this hypothesis. A recent publication that claims montamine and 4,4'-bismoschamine are not the same natural product prompts us to disclose our own findings on this matter. A biomimetic synthesis of 4,4'-bismoschamine was developed that hinged on oxidative coupling of N-Boc-serotonin followed by elaboration of the resulting 4,4'-dimer to the natural product. A detailed comparison of the NMR data for synthetic 4,4'-bismoschamine with that reported for montamine revealed that while the 1H NMR data were in good agreement, the 13C NMR data displayed some discrepancies. In light of this result, the NMR data for several literature compounds was analyzed, the results of which revealed that the upfield chemical shifts of the methylene protons in the 1H NMR of montamine is unique to 4,4'-bistryptamines, supporting our initial statement that montamine and 4,4'-bismoschamine are structurally equivalent. Given that the main differences in the 13C NMR data between montamine and synthetic 4,4'-bismoschamine occur at the quaternary carbons, we propose that these peaks have been misassigned from a 13C NMR spectrum that was obtained from an impure sample and/or the small amount of montamine (4 mg) isolated from the natural source.
Assuntos
Biomimética/métodos , Serotonina/análogos & derivados , Produtos Biológicos/síntese química , Produtos Biológicos/química , Técnicas de Química Sintética/métodos , Dimerização , Indóis/química , Espectroscopia de Ressonância Magnética , Acoplamento Oxidativo , Óleo de Cártamo/química , Serotonina/síntese química , Serotonina/química , Triptaminas/químicaRESUMO
Methicillin-resistant Staphylococcus aureus pyruvate kinase (MRSA PK) has recently been identified as a target for development of novel antibacterial agents. Testing a series of 1,2-bis(3-indolyl)ethanes against MRSA PK has led to the discovery of a potent inhibitor that is selective over human isoforms.
Assuntos
Antibacterianos/química , Inibidores Enzimáticos/química , Etano/química , Piruvato Quinase/antagonistas & inibidores , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Etano/metabolismo , Etano/farmacologia , Humanos , Indóis/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Ligação Proteica , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Piruvato Quinase/metabolismoRESUMO
The natural product montamine was originally assigned as a homodimer of moschamine linked by a N-N' bond at the serotonin side-chain. A total synthesis of the reported structure has shown this to be incorrect. Analysis of the spectroscopic data suggests that the dimerization site has been incorrectly assigned, and montamine is likely to be a 4,4'-bismoschamine natural product previously described in the literature.
Assuntos
Química Farmacêutica/métodos , Ácidos Cumáricos/síntese química , Alcaloides Indólicos/síntese química , Produtos Biológicos/química , Dimerização , Desenho de Fármacos , Éteres/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Prótons , Serotonina/química , Espectrofotometria/métodos , EstereoisomerismoRESUMO
As of early 2013, over 200 natural products are known to contain a nitrogen-nitrogen (N-N) bond. This report categorizes these compounds by structural class and details their isolation and biological activity.
Assuntos
Produtos Biológicos , Nitrogênio/química , Produtos Biológicos/química , Produtos Biológicos/classificação , Produtos Biológicos/farmacologia , Estrutura MolecularRESUMO
The flavoalkaloids possess unique molecular frameworks that contain both a flavonoid and alkaloid component. Flavoalkaloids result from the convergence of distinct biosynthetic pathways, affording natural products that display a wide range of interesting biological activities that would not be expected for flavonoids or alkaloids alone. This chapter collates all the known flavoalkaloids up until early 2016, detailing their isolation, bioactivity, and successful total syntheses.
Assuntos
Alcaloides , Alcaloides/síntese química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Produtos Biológicos , Estrutura Molecular , EstereoisomerismoRESUMO
The spiroindimicins are a family of structurally unprecedented alkaloids isolated from the deep-sea-derived marine actinomycete Streptomyces sp. SCSIO 03032. The total syntheses of (±)-spiroindimicins B and C are disclosed, the first of any member of this family. Central to the successful strategy was installing the spirocentre using a mild intramolecular Heck reaction, the assembly of a pentacyclic spirobisindole by Fischer indolization and a late-stage Schöllkopf-Magnus-Barton-Zard (SMBZ) reaction to construct the trisubstituted pyrrole.