determination of absolute configuration
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Conventional Nuclear Magnetic Resonance (NMR) analysis relies on H-H/C-H interactions. However, these interactions are sometimes insufficient for an accurate and precise NMR analysis. In this study, we show that 31P NMR parameters can provide critical structural insights into the stereochemistry of phosphorus-containing compounds. For this purpose, we prepared a set of model phosphorus-based proline derivatives, separated diastereoisomers, and determined their absolute configuration by single-crystal X-ray diffraction. After supplementing these results by electronic circular dichroism (ECD) spectroscopy, we combined experimental data and DFT calculations from our model compounds to perform a detailed conformational analysis, thereby determining their relative configuration. Overall, our findings establish an experimental paradigm for combining 31P NMR spectroscopy with other optical methods to facilitate the stereochemical analysis of phosphorus-containing compounds.
Twenty known Amaryllidaceae alkaloids of various structural types, and one undescribed alkaloid of narcikachnine-type, named narcieliine (3), have been isolated from fresh bulbs of Zephyranthes citrina. The chemical structures of the isolated alkaloids were elucidated by a combination of MS, HRMS, 1D and 2D NMR, and CD spectroscopic techniques, and by comparison with literature data. The absolute configuration of narcieliine (3) has also been determined. Compounds isolated in a sufficient quantity were evaluated for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7), butyrylcholinesterase (BuChE; E.C. 3.1.1.8), and prolyl oligopeptidase (POP; E.C. 3.4.21.26) inhibition activities. Significant human AChE/BuChE (hAChE/hBuChE) inhibitory activity was demonstrated by the newly described alkaloid narcieliine (3), with IC50 values of 18.7 ± 2.3 µM and 1.34 ± 0.31 µM, respectively. This compound is also predicted to cross the blood-brain barrier (BBB) through passive diffusion. The in vitro data were further supported by in silico studies of 3 in the active site of hAChE/hBuChE.
- MeSH
- acetylcholinesterasa chemie metabolismus MeSH
- alkaloidy chemie izolace a purifikace farmakologie terapeutické užití MeSH
- Alzheimerova nemoc farmakoterapie patologie MeSH
- Amaryllidaceae chemie metabolismus MeSH
- butyrylcholinesterasa chemie metabolismus MeSH
- cholinesterasové inhibitory chemie metabolismus farmakologie terapeutické užití MeSH
- hematoencefalická bariéra účinky léků metabolismus MeSH
- katalytická doména MeSH
- kinetika MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární konformace MeSH
- simulace molekulového dockingu MeSH
- vazebná místa MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Prenylated or geranylated flavonoids have been studied for their promising antiproliferative and cytotoxic activities. Twelve natural geranylated flavonoids (1-12) were isolated from the fruit of Paulownia tomentosa Steud. Their structures were elucidated using UV and IR spectroscopy, mass spectrometry, and 1D and 2D NMR spectroscopy. The absolute configurations were determined using NMR and circular dichroism. Seven of the compounds were characterized as new geranylated derivatives isolated from a natural source for the first time, namely 3'-O-methyl-5'-hydroxyisodiplacone (3), paulodiplacone A (5), tomentone II (6), tomentone B (7), tomentodiplacone P (8), paulodiplacone B (9), and tomentoflavone A (12). After 24 h of incubation at concentrations in the range 1-30 μM, the isolated compounds were tested for their antiproliferative and cytotoxic potentials against the human monocytic leukaemia cell line THP-1, using WST-1 and LDH assays, respectively. Almost all of the test compounds induced a concentration-dependent reduction in the metabolic activity of THP-1 cells and a concentration-dependent reduction in the cell viability. Diplacone (1) was the most potent antiproliferative and cytotoxic agent (IC50 9.31 ± 0.72 μM, LC50 18.01 ± 1.19 μM). 3'-O-Methyl-5'-hydroxydiplacone (2) showed relatively strong antiproliferative effect (IC50 12.61 ± 0.90 μM) and weaker cytotoxic activity (LC50 > 30 μM), indicating that it may serve as a potential lead compound for further testing. The structure-activity relationship for the 12 isolated compounds is discussed.
- MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- fytogenní protinádorové látky chemie izolace a purifikace farmakologie MeSH
- lidé MeSH
- Magnoliopsida chemie MeSH
- molekulární struktura MeSH
- nádorové buňky kultivované MeSH
- ovoce chemie MeSH
- proliferace buněk účinky léků MeSH
- rostlinné extrakty chemie izolace a purifikace farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The bumblebee wax moth, Aphomia sociella, is a parasite of bumblebees. In this species, males produce sexual pheromone to attract females, while females produce an aphrodisiac pheromone that initiates male courtship. Both pheromones contain 6,10,14-trimethylpentadecan-2-one (TMPD-one) and the corresponding alcohol, 6,10,14-trimethylpentadecan-2-ol (TMPD-ol) in sex specific quantities. Male sex pheromone consists of 7 components with TMPD-one as a minor one and traces of TMPD-ol. In female aphrodisiac pheromone, TMPD-ol is the major component, while TMPD-one is present in traces. Here we report on the absolute configuration of TMPD-one in male sex pheromone and TMPD-ol in female aphrodisiac pheromone of A. sociella. The configuration was determined from GC/MS of prepared (S)-acetoxypropionyl esters of TMPD-ol. TMPD-one was first reduced to the alcohol that was then derivatized with (S)-acetoxypropionyl chloride. The GC/MS data of obtained diastereoisomers were compared with synthetic standards. The absolute configuration of TMPD-one in the male pheromone was (6R,10R). The configuration of TMPD-ol in the female pheromone was (2R,6R,10R). Electrophysiological experiments showed that TMPD-one and TMPD-ol are perceived by both sexes. The synthetic standards of naturally produced stereoisomers elicited higher responses than mixtures of all stereoisomers.
- MeSH
- můry metabolismus MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- sexuální lákadla chemie izolace a purifikace MeSH
- stereoizomerie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Two new isoquinoline alkaloids, named fumaranine (2) and fumarostrejdine (10), along with 18 known alkaloids were isolated from aerial parts of Fumaria officinalis. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses and by comparison with literature data. The absolute configuration of the new compound 2 was determined by comparing its circular dichroism spectra with those of known analogs. Compounds isolated in sufficient amounts were evaluated for their acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase (POP), and glycogen synthase kinase-3β inhibitory activities. Parfumidine (8) and sinactine (15) exhibited potent POP inhibition activities (IC50 99±5 and 53±2 μM, resp.).
- MeSH
- acetylcholinesterasa metabolismus MeSH
- alkaloidy chemie izolace a purifikace farmakologie MeSH
- Alzheimerova nemoc farmakoterapie enzymologie MeSH
- butyrylcholinesterasa metabolismus MeSH
- Fumaria chemie MeSH
- inhibitory enzymů chemie izolace a purifikace farmakologie MeSH
- isochinoliny chemie izolace a purifikace farmakologie MeSH
- kinasa 3 glykogensynthasy antagonisté a inhibitory metabolismus MeSH
- lidé MeSH
- molekulární struktura MeSH
- serinové endopeptidasy metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The structures of two stereoisomers of the chiral anion [VO2(N-salicylidene-isoleucinato)](-) possessing three centers of chirality, the vanadium atom (configuration A/C) and the isoleucine moiety (configuration R/S on alpha and beta carbons), are presented. The absolute configuration of all available stereosiomers, CSS, ARR, CSR and ARS, was determined by electronic circular dichroism (ECD), which allows distinguishing between diastereomers, and by vibrational circular dichroism (VCD) capable of differentiating between all four stereoisomers. The comparison of experimental VCD and infrared (IR) spectra with simulated spectra for band assignment revealed the IR spectra of the diastereomers differing significantly in the CH stretching region of the aromatic part in the molecule. Crystallization from binary systems composed of equal ratio of two stereoisomers of isoleucine, unveiled the lower solubility of CSS and ARR stereoisomers, while a longer crystallization time of the CSR and ARS stereoisomers allowed proceeding the vanadium-catalyzed epimerization, leading to the subsequent presence of the CSS and ARR stereoisomers in the product obtained.
- MeSH
- isomerie MeSH
- komplexní sloučeniny chemie MeSH
- Schiffovy báze chemie MeSH
- vanad chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Silybin, a secondary metabolite isolated from the seeds of the blessed milk thistle (Silybum marianum) was discovered as the first member of a new family of natural compounds called flavonolignans in 1959. Over the years it has received the research attention of many organic chemists. This research has resulted in a number of semisynthetic derivatives prepared in an effort to modulate and better target the biological activities of silybin or to improve its physical properties, such as its solubility. A fundamental breakthrough in silybin chemistry was the determination of the absolute configurations of silybin A and silybin B, and the development of methods for their separation. This review covers articles dealing with silybin chemistry and also summarizes all the derivatives prepared.
Exhaustive chromatographic separation of the chloroform portion of the ethanolic extract obtained from Paulownia tomentosa (Thunb). Steud. (Paulowniaceae) fruits has led to isolation of ten C-6 geranylated flavanones tomentodiplacone C-I and mimulone C-E, featured by 3'-methoxy and 4'-hydroxy or 4'-hydroxy substitution of the B-ring of the flavonoid, respectively. The structures of these compounds were determined by using mass spectrometry (including HRMS) and 1D and 2D NMR spectroscopy. The absolute configurations of the compounds at C-2 were determined using circular dichroism. The obtained compounds showed the presence of a geranyl moiety functionalized by a carbonyl, hydroxyl or methoxyl group, or by formation of tetrahydrofuran or fused-pyrane ring, respectively. All of the flavanones described were isolated for the first time from a natural source. The antibacterial activities of selected compounds isolated along with the previously isolated geranylated flavanones were evaluated against a common panel of microbes and MRSA strains. The selected isolated compounds were tested for their ability to affect eukaryotic translation initiation via dual-luciferase reporter assay (firefly and renilla).
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- flavanony chemie farmakologie MeSH
- iniciace translace peptidového řetězce účinky léků MeSH
- luciferasy genetika MeSH
- Magnoliopsida chemie MeSH
- methicilin rezistentní Staphylococcus aureus účinky léků MeSH
- mikrobiální testy citlivosti MeSH
- ovoce chemie MeSH
- reportérové geny genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Identification of molecular species of various N-acylated bacteriohopanehexol-mannosamides from the thermophilic bacterium Alicyclobacillus acidoterrestris by semipreparative HPLC and by RP-HPLC with ESI is described. We used triple-quadrupole type mass spectrometer, (1)H and (13)C NMR for analyzing this complex lipid. CD spectra of two compounds (model compound--7-deoxy-D: -glycero-D: -allo-heptitol obtained by stereospecific synthesis, and an isolated derivative of hopane) were also measured and the absolute configuration of both compounds was determined. On the basis of all the above methods, we identified the full structure of a new class of bacteriohopanes, represented by various N-acylated bacteriohopanehexol-mannosamides.
- MeSH
- acylace MeSH
- Alicyclobacillus chemie růst a vývoj MeSH
- amidy analýza chemie izolace a purifikace MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- magnetická rezonanční spektroskopie MeSH
- mannosa analýza chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- tandemová hmotnostní spektrometrie MeSH
- teplota MeSH
- triterpeny analýza chemie izolace a purifikace MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
