RESUMO
BODIPYs have a well-established role in biological sciences as chemosensors and versatile biological markers due to their chemical reactivity, which allows for fine-tuning of their photophysical characteristics. In this work, we combined the unique reactivity of arylazo sulfones with the advantages of a "sunflow" reactor to develop a fast, efficient, and versatile method for the photochemical arylation of BODIPYs and other chromophores. This approach resulted in red-shifted emitting fluorophores due to extended electronic delocalization at the 3- and 5-positions of the BODIPY core. This method represents an advantageous approach for BODIPY functionalization compared to existing strategies.
RESUMO
INTRODUCTION: The genus Omphalotus, in particular the "Jack-O'Lantern mushrooms" Omphalotus illudens and Omphalotus olearius, are famous for the production of the DNA-alkylating illudins. A lesser-known species, Omphalotus mexicanus, native to Central America, also produces cytotoxic illudins S and M, but its minor secondary metabolites are yet to be investigated. OBJECTIVE: To identify, isolate, and elucidate the structure of novel secondary metabolites of the illudin family in mycelial extracts of O. mexicanus from submerse cultivation. METHODOLOGY: A fermentation of the fungus in 15 L stirred tank bioreactors is described. Mycelial extracts were separated using a combination of flash chromatography with preparative RP-C18 high-performance liquid chromatography (HPLC). Analysis of metabolites was done using an ultrahigh-performance liquid chromatography ultraviolet diode array detector (UPLC-UV-DAD) system coupled to an electrospray ionisation quadrupole time-of-flight (ESI-QTOF) mass spectrometer. Structures were elucidated using one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance spectroscopy (NMR) techniques followed by comparison of experimental and simulated electronic circular dichroism (ECD) spectra to determine absolute configurations. RESULTS: Two novel illudin derivatives, for which we propose the names omphaderol (1) and illudaneol B (2), as well as illudaneol (3) and the unusual cyclobutylcyclopentane illudosin (4), were isolated from the mycelia and characterised. CONCLUSION: Particularly the illudaneol derivatives with their high titers may be potential building blocks for an alternative semisynthetic route to new illudin derivatives with improved medical properties. Additionally, the findings improve the knowledge of minor illudin compounds in the mycelial extract of this fungus and may be of significance for future biosynthetic studies of the illudins.
Assuntos
Agaricales , Espectrometria de Massas por Ionização por Electrospray , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida/métodos , Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
Reactions involving C(sp3)-H bonds of azaarenes have been widely studied in recent years as they allow direct functionalization of these N-heterocycles without the use of harsh reaction conditions. In this work, we describe the C(sp3)-H functionalization of 4-methylquinazolines and 1-benzylisoquinolines, employing α-substituted ß-nitrostyrenes catalyzed by inexpensive copper acetate. Under the optimized condition, 21 pyrrolo[1,2-c]quinazolines, as well as an imidazo[1,2-c]quinazoline and 4 pyrrolo[2,1-a]isoquinolines, were obtained in moderate to good yields. Furthermore, the biological activity of the pyrrolo[1,2-c]quinazolines was evaluated against Plasmodium falciparum, and promising results were obtained.
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Antimaláricos , Quinazolinas , Cobre/farmacologia , Cobre/química , Isoquinolinas/química , CatáliseRESUMO
This article discusses the reactivity of 6-azaindazole (1) and 2,6-naphthyridine (2), proposed to be "heteroaromatic rings of the future," which would be useful for fragment-based drug discovery (FBDD) campaigns, developing growth vectors for fragment elaboration by selectively functionalizing different positions on the rings. The pyridone oxygens and pyrazole nitrogen can be functionalized selectively. Arylation at the α-carbon of the pyridone moiety was achieved by a transition metal-free radical cross-coupling using aryl hydrazines. This method proceeded under mild conditions without the need for protection of the hydroxypyridine. Additionally, we developed a method for the regioselective C-3 functionalization of heterocycle 1via N-sulfonamide rearrangement. This method involved a novel regioselective base-mediated N-C migration of the N-1 sulfonamide to yield the C-3 sulfone. This procedure is also applicable for indazole C-3 functionalization and mechanistic studies of the rearrangement suggest that an intermolecular process is involved. These reactions enable the fragment elaboration of heterocycles 1 and 2 in several growth vectors to facilitate their use in FBDD.
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Carbono , Nitrogênio , Catálise , Hidrazinas , Indazóis , Naftiridinas , Pirazóis , Piridonas , Sulfonamidas , SulfonasRESUMO
INTRODUCTION: Triterpenes are one of the largest secondary metabolites groups spread in the plant kingdom with various skeletons. These metabolites have showed various bioactivities including anti-inflammatory activity. OBJECTIVE: The study aims to explore the mass spectrometry fragmentation of donellanic acids A-C (DA A-C), three compounds identified from Donella ubanguiensis; in addition, the fragmentation behaviour of these metabolites will serve as a fingerprint to search and characterise triterpenes congeners in fruits, bark and wood crude extracts of D. ubanguiensis. This work was prompted by the anti-inflammatory activity on leukocyte migration, exudate concentrations and myeloperoxidase activity obtained for DA A-B. METHODOLOGY: The bioactivity was performed on mouse model of pleurisy induced by carrageenan and the parameters were analysed by veterinarian automated cell counter and colorimetric assays. While the tandem mass analyses of DA A-C were carried out by a direct infusion ESI-QTOF-MS/MS, the extracts were studied by UPLC-ESI-QTOF-MS and UPLC-ESI-QTOF-MS/MS. RESULTS: DA A displayed interesting anti-inflammatory activity by inhibiting leukocyte migration, exudate concentrations and myeloperoxidase activity (p < 0.05) while DA B was weakly active (p > 0.05). Moreover, the diagnostic of the MS2 behaviour of DA A-C in conjunction with the chromatograms and the obtained MS2 data of the crude extract led to the characterisation of three cyclopropane triterpenes (T1-T3) and six saponins (T4-T9) from the fruits, the bark, and the wood extracts. CONCLUSIONS: Donella species deserve more investigation since metabolites related to the anti-inflammatory compound (DA A) could be identified. Copyright © 2016 John Wiley & Sons, Ltd.
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Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Ciclopropanos/química , Magnoliopsida/metabolismo , Espectrometria de Massas por Ionização por Electrospray/métodos , Triterpenos/análise , Triterpenos/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Quimiotaxia de Leucócito/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Feminino , Camundongos , Peroxidase/antagonistas & inibidores , Pleurisia/induzido quimicamente , Pleurisia/tratamento farmacológico , Triterpenos/uso terapêuticoRESUMO
The ascomycones A-C (1-3), three novel heptaketide-derived secondary metabolites, have been isolated from cultures of an unknown ascomycete. While 1 and 2 are closely related pyranonaphthoquinones, 3 has a bicyclic dihydronaphthoquinone core. Compounds 2 and 3 exhibited significant activity against several phytopathogenic fungi.