883 results on '"diastereomers"'
Search Results
2. Chirality descriptors for structure–activity relationship modeling of bioactive molecules.
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Natarajan, Ramanathan, Lungu, Claudiu N., and Basak, Subhash C.
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CHIRAL centers , *BIOMACROMOLECULES , *DRUG target , *SPATIAL arrangement , *DIASTEREOISOMERS , *DOPAMINE receptors - Abstract
Owing to the homochirality among the α-amino acids, the building blocks, chiral environmental prevails within the structure of biological macromolecules namely, the proteins, receptors, and enzymes. This results in chiral distinction of the ligands such as drug molecules and toxicants by the biological targets. Chiral distinction of enantiomers is not only important in the biological activity of enantiomers but also in pharmacokinetics and metabolism of chemicals. The molecular descriptors that are based only on the connectivity of atoms cannot differentiate the enantiomers and diastereomers. In order to model the differential activity of enantiomers and diastereomers, molecular descriptors capable of encoding the difference in spatial arrangements of atoms and groups around a chiral center are needed. In this paper we report a modified approach that enables to compute a large pool of chirality descriptors for a given set of molecules. The new chirality descriptors can differentiate enantiomers and diastereomers. Application of the new chiral descriptors in structure–activity modelling of bioactivity of chiral molecules is illustrated for the dopamine (DA) D2 and opiate σ receptor affinities of seven pairs of enantiomers of 3-(3-hydroxyphenyl)piperidines. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Synthesis of Novel Planar-Chiral Charge-Compensated nido -Carborane-Based Amino Acid.
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Gruzdev, Dmitry A., Telegina, Angelina A., Ezhikova, Marina A., Kodess, Mikhail I., Levit, Galina L., and Krasnov, Victor P.
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ZWITTERIONS , *PLANAR chirality , *PEPTIDES , *AMINO acids , *AMINO group - Abstract
Amino acids with unusual types of chirality and their derivatives have recently attracted attention as precursors in the synthesis of chiral catalysts and peptide analogues with unique properties. In this study, we have synthesized a new nido-carborane-based planar-chiral amino acid, in the molecule of which the amino group is directly bonded to the B(3) atom, and the carboxyl group is attached to the B(9) atom through the CH2S+(Me) fragment. 3-Amino-9-dimethylsulfonio-nido-carborane, prepared in three steps from 3-amino-closo-carborane in a high yield, was a key intermediate in the synthesis of the target planar-chiral amino acid. The carboxymethyl group at the sulfur atom was introduced by the demethylation reaction of the dimethylsulfonio derivative, followed by S-alkylation. The structure of new 3,9-disubstituted nido-carboranes was studied for the first time using NMR spectroscopy. The resonances of all boron atoms in the 11B NMR spectrum of 3-amino-9-dimethylsulfonio-nido-carborane were assigned based on the 2D NMR correlation experiments. The nido-carborane-based planar-chiral amino acid and related compounds are of interest as a basis for peptide-like compounds and chiral ligands. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Analysis of cis-isomer-enriched dihydroquercetin sample by 1D and 2D NMR spectroscopy
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R. P. Terekhov, A. Taldaev, E. V. Bocharov, D. I. Pankov, A. D. Savina, and I. A. Selivanova
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taxifolin ,flavonoids ,stereoisomerism ,diastereomers ,nmr spectroscopy ,pharmaceutical analysis ,Pharmaceutical industry ,HD9665-9675 - Abstract
Introduction. The structure of dihydroquercetin (DHQ) is characterized by two chiral centers at positions 2 and 3 of the benzopyran cycle, resulting in possible diastereomers: trans- and cis-isomers. Therefore, the development of methods for qualitative and quantitative control of DHQ diastereomers in analyzed samples is essential for patient safety management. Nuclear magnetic resonance (NMR) spectroscopy is one of the physicochemical methods that can be used for this purpose.Aim. The study objective was to accumulate the analytical and structural characteristics of cis-DHQ by NMR spectroscopy of the spheroidal form of this flavonoid (DHQs).Materials and Methods. 1D 1H, 1H,1H-COSY, 1H,1H-NOESY, and 1H,13C-HSQC NMR spectra were acquired at 298 K on an 800 MHz NMR spectrometer equipped with a TXI triple resonance probe. The number of scans was 32. The mixing time in the NOESY experiment was 400 ms. The 1H and 13C were analyzed using CcpNmr software. The dihedral angles were calculated by applying the Karplus equation.Results and discussion. In trans-DHQ, the chemical shift values for H2 and H3 are 4.93 ppm and 4.52 ppm, respectively, and in cis-DHQ they are 5.31 ppm and 4.20 ppm, respectively. The spin-spin coupling constants between H2 and H3 of trans- and cis-DHQ are 12.00 Hz and 2.40 Hz, respectively. Thus, the dihedral angles for the trans- and cis-isomers are 154° and 64°, respectively. We found that DHQs contains 12.5 % of the cis-isomer.Conclusion. Our experiments confirmed that NMR spectroscopy can discriminate between trans- and cis-DHQ based on the chemical shift values for the cross-peaks of H2 and H3. The second major finding was that this method can be considered as a more selective quantitative analysis than HPLC with UV detection without reference. One of the most important results of this study for drug development is the updated information on the structural parameters of DHQ diastereomers in the liquid phase.
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- 2024
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5. Synthesis and spatial structure of 3,7-dihydroxy-7-(trifluoromethyl)hexahydropyrrolo[1,2-a]pyrimidines.
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Goryaeva, M. V., Ezhikova, M. A., Burgart, Ya. V., Kustova, M. S., Kodess, M. I., Slepukhin, P. A., and Saloutin, V. I.
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METHYL ethyl ketone , *METHYL ketones , *PYRIMIDINES , *DIASTEREOISOMERS , *X-ray diffraction - Abstract
A characteristic feature of the three-component cyclization of ethyl trifluoropyruvate and methyl ketones with 1,3-diamino-2-propanol is the formation of 8a-alkyl(phenyl)-3,7-dihydroxy-7-(trifluoromethyl)hexahydropyrrolo[1,2-a]pyrimidin-6(2H)-ones as one, two, or three diastereomers, depending on the methyl ketone component. The structures of the new heterocycles were established using the data of X-ray diffraction and 1H and 13C NMR spectra, including 2D 1H—13C HSQC, HMBC, 1H—1H COSY, and NOESY experiments. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Synthesis of (η6-Arene)tricarbonylchromium Complexes of 1,3-Benzodioxanes.
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Grishina, N. Yu., Sazonova, E. V., Ushakova, P. S., Somov, N. V., Medvedeva, E. A., Shishkin, A. Yu., and Artemov, A. N.
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MOLECULAR structure , *NUCLEAR magnetic resonance spectroscopy , *MASS spectrometry , *X-ray diffraction , *HETEROCYCLIC compounds - Abstract
The reactions of triammino(tricarbonyl)chromium (I) with 1,3-benzodioxane (L1), 2-methyl-1,3-benzodioxane (L2), and 2-phenyl-1,3-benzodioxane (L3) afford new complexes: (η6-C8H8O2)Cr(CO)3 (II), exo- and endo-[2-Me-(η6-C8H7O2)]Cr(CO)3 (III, IV), exo- and endo-[2-Ph-(η6-C8H7O2)]Cr(CO)3 (V, VI), [2-(η6-Ph)-C8H7O2]Cr(CO)3 (VII), and endo-[2-(η6-Ph)]Cr(CO)3-[η6-C8H7O2]Cr(CO)3 (VIII). The structures, compositions, and purity of the synthesized products are proved by UV, IR, and 1H NMR spectroscopy, HPLC, and mass spectrometry. The molecular structures of complexes IV–VI are determined by XRD (CIF files CCDC nos. 2263301 (IV), 2295552 (V), and 2237106 (VI)). A possibility of coordination of the tricarbonylchromium group at different sides of the phenylene ring of ligands L2 and L3 and on the phenyl substituent of ligand L3 is shown. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Asymmetric synthesis, characterization of chiral trans and cis-3-chloro/oxo/thio-4-styryl-β-lactams using (R)-(+)-1-phenylethylamine and their efficient column chromatographic separation.
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Kumari, Anu, Garg, Ankita, Sahoo, Subash Chandra, and Bhalla, Aman
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LACTAMS , *ACETIC acid , *COUPLING constants , *COLUMN chromatography , *X-ray crystallography , *KETENES , *DIASTEREOISOMERS , *ASYMMETRIC synthesis - Abstract
Diverse chiral trans and cis-3-chloro/oxo/thio-4-styryl-β-lactams were efficiently synthesized using chiral 3′-phenylallylidene-[(R)-1′-phenylethyl] amine and substituted ethanoic acids. Moore ketenes derived from chloro/phenythio/benzylthio ethanoic acids (Cl/PhS/BzS) affords both chiral trans- and cis β-lactams, with a preference for trans-stereochemistry. However, Bose-Evans ketenes obtained from 2-methoxy/phenoxyethanoic acids (MeO/PhO), led to the exclusive formation of cis-diastereomers only. Further, individual diastereomers of trans- and cis-β-lactams were separated via efficient column chromatography. The relative cis and trans configuration of the C-3 and C-4 protons in chiral β-lactams was established using coupling constant value ranging from J = 1.4 to 2.1 Hz (in case of trans) and J = 4.3 to 5.2 Hz (in case of cis) respectively. Structural confirmation of β-lactams was done using FT-IR, NMR (1H,13C,1H-1H COSY and 1H-13C HSQC), elemental analysis, ESI-MS and X-ray crystallography. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Diastereomers of Spheroidal Form and Commercially Available Taxifolin Samples.
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Terekhov, Roman P., Melnikov, Evgeny S., Nikitin, Ilya D., Tokareva, Margarita A., Rodina, Tatyana A., Savina, Anastasiya D., Pankov, Denis I., Zhevlakova, Anastasiya K., Beloborodov, Vladimir L., and Selivanova, Irina A.
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DIASTEREOISOMERS , *SOLID dosage forms , *GRADIENT elution (Chromatography) , *CHIRAL centers , *FORMIC acid - Abstract
Taxifolin is a natural polyphenol belonging to the class of flavonoids. The structure of this compound is characterized by the presence of two chiral centers. The spheroidal form of taxifolin (TAXs) has emerged as a promising modification due to enhanced solubility, higher safety profile, and long-term release from solid dosage forms. The study's objective was to assess the diastereomeric content in TAXs and industrially produced samples of taxifolin. Considering the difference in the physico-chemical properties of diastereomers and based on the literature data, we developed a qualitative HPLC method. The chromatograms were recorded using a diode array detector at 290 nm and a mass spectrometer operated in negative ionization mode. Our data suggest that a biphenyl column and gradient elution using 0.1% formic acid in water and 0.2% formic acid in methanol, with the organic phase gradient from 7% to 21% and a flow rate of 0.65 mL/min for 15 min at 60 °C, provides the best conditions for the separation of taxifolin diastereomers. This method was validated for quantitative analysis. We discovered that the cis-isomer was present in all the analyzed samples, with its quantity ranging from 0.8% to 9.5%. TAXs can be considered a sample enriched with diastereomers. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Assignment of NMR spectral data of diastereomeric tetrahydrofuranyl acetals directly from their mixture by spectral simulation
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Nešić Milan S., Nešić Milica D., and Radulović Niko S.
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tetrahydrofuran ,citronellol ,spectral assignment ,spin simulation ,diastereomers ,mixture ,Chemistry ,QD1-999 - Abstract
In this study, an NMR spectral analysis of the mixture of diastereomeric acetals, synthesized from 2,3-dihydrofurane and a racemic mixture of citronellol, was performed. 1H-NMR full spin analysis was achieved by manually adjusting δH and J values (previously calculated using the Spartan software) to fit the experimentally available values, followed by further optimization using MestreNova software. The simulated 1H- and 13C-NMR spectra of individual diastereomers, as well as their superimposed and summed spectra, were compared with the obtained experimental spectra. Spin simulation of proton signals was particularly useful for the assignment of the diastereotopic protons of tetrahydrofuranyl moiety and diastereomer discrimination. The NMR spectral data of individual diastereomers – chemical shifts, coupling constants, HMBC and NOESY interactions were systematized in appropriate tables and schemes. To the best of our knowledge, this is for the first time that the complete assignment of tetrahydrofuranyl moiety was performed, and the data obtained herein may be of great importance for the utilization of this protecting group in the future.
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- 2024
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10. Synthesis of Novel Planar-Chiral Charge-Compensated nido-Carborane-Based Amino Acid
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Dmitry A. Gruzdev, Angelina A. Telegina, Marina A. Ezhikova, Mikhail I. Kodess, Galina L. Levit, and Victor P. Krasnov
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alkylation ,amino acid ,diastereomers ,7,8-dicarba-nido-undecaborane ,NMR spectral assignment ,planar chirality ,Organic chemistry ,QD241-441 - Abstract
Amino acids with unusual types of chirality and their derivatives have recently attracted attention as precursors in the synthesis of chiral catalysts and peptide analogues with unique properties. In this study, we have synthesized a new nido-carborane-based planar-chiral amino acid, in the molecule of which the amino group is directly bonded to the B(3) atom, and the carboxyl group is attached to the B(9) atom through the CH2S+(Me) fragment. 3-Amino-9-dimethylsulfonio-nido-carborane, prepared in three steps from 3-amino-closo-carborane in a high yield, was a key intermediate in the synthesis of the target planar-chiral amino acid. The carboxymethyl group at the sulfur atom was introduced by the demethylation reaction of the dimethylsulfonio derivative, followed by S-alkylation. The structure of new 3,9-disubstituted nido-carboranes was studied for the first time using NMR spectroscopy. The resonances of all boron atoms in the 11B NMR spectrum of 3-amino-9-dimethylsulfonio-nido-carborane were assigned based on the 2D NMR correlation experiments. The nido-carborane-based planar-chiral amino acid and related compounds are of interest as a basis for peptide-like compounds and chiral ligands.
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- 2024
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11. Synthesis of (η6-Arene)tricarbonylchromium Complexes of 1,3-Benzodioxanes
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Grishina, N. Yu., Sazonova, E. V., Ushakova, P. S., Somov, N. V., Medvedeva, E. A., Shishkin, A. Yu., and Artemov, A. N.
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- 2024
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12. Computational insights into the stereo-selectivity of catechins for the inhibition of the cancer therapeutic target EGFR kinase.
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Rehan, Mohd, Ahmed, Firoz, Khan, Mohammad Imran, Ansari, Hifzur Rahman, Shakil, Shazi, El-Araby, Moustafa E., Hosawi, Salman, and Saleem, Mohammad
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CATECHIN ,EPIDERMAL growth factor receptors ,MOLECULAR dynamics ,STEREOISOMERS ,CHIRAL centers ,CHEMICAL properties - Abstract
The epidermal growth factor receptor (EGFR) plays a crucial role in regulating cellular growth and survival, and its dysregulation is implicated in various cancers, making it a prime target for cancer therapy. Natural compounds known as catechins have garnered attention as promising anticancer agents. These compounds exert their anticancer effects through diverse mechanisms, primarily by inhibiting receptor tyrosine kinases (RTKs), a protein family that includes the notable member EGFR. Catechins, characterized by two chiral centers and stereoisomerism, demonstrate variations in chemical and physical properties due to differences in the spatial orientation of atoms. Although previous studies have explored the membrane fluidity effects and transport across cellular membranes, the stereo-selectivity of catechins concerning EGFR kinase inhibition remains unexplored. In this study, we investigated the stereo-selectivity of catechins in inhibiting EGFR kinase, both in its wild-type and in the prevalent L858R mutant. Computational analyses indicated that all stereoisomers, including the extensively studied catechin (-)-EGCG, effectively bound within the ATPbinding site, potentially inhibiting EGFR kinase activity. Notably, gallated catechins emerged as superior EGFR inhibitors to their non-gallated counterparts, revealing intriguing binding trends. The top four stereoisomers exhibiting high dock scores and binding energies with wild-type EGFR comprise (-)-CG (-)-GCG (+)-CG, and (-)-EGCG. To assess dynamic behavior and stability, molecular dynamics simulations over 100 ns were conducted for the top-ranked catechin (-)-CG and the widely investigated catechin (-)-EGCG with EGFR kinase. This study enhances our understanding of how the stereoisomeric nature of a drug influences inhibitory potential, providing insights that could guide the selection of specific stereoisomers for improved efficacy inexisting drugs. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Synthesis of Novel Phosphorus-Containing Derivatives of 1,3,4-Trimethylglycoluril via the Birum–Oleksyszyn Reaction.
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Gorbin, Sergey I., Bakibaev, Abdigali A., Tuguldurova, Vera P., Kotov, Andrey V., Sysoev, Gleb O., Potapov, Andrei S., Pavlov, Dmitry I., Malkov, Victor S., Knyazev, Alexey S., Kurgachev, Dmitriy A., and Michalchenkov, Mark V.
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ANALYTICAL chemistry , *BENZALDEHYDE , *DIASTEREOISOMERS , *CRYSTAL structure - Abstract
This work presents the synthesis of a new compound, 1-[aryl-(diphenylphosphono)methyl]-3,4,6-trimethylglycolurils, via the interaction of benzaldehyde and its mononitro- and monohydroxyderivatives with 1,3,4-trimethylglycoluril and triphenylphosphite. By varying the reaction conditions and the catalysts, the obtained product yields ranged from satisfactory to good. The diastereomers formed during the reaction were separated by semipreparative HPLC on the C18 stationary phase. The isolated diastereomers were characterized by 1H, 13C, and 31P NMR, and the structures of the diastereomers were confirmed using a single-crystal X-ray crystal structure analysis and quantum chemical calculations. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Chirality
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Blackmond, Donna, Gargaud, Muriel, editor, Irvine, William M., editor, Amils, Ricardo, editor, Claeys, Philippe, editor, Cleaves, Henderson James, editor, Gerin, Maryvonne, editor, Rouan, Daniel, editor, Spohn, Tilman, editor, Tirard, Stéphane, editor, and Viso, Michel, editor
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- 2023
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15. An efficient synthesis of substituted 4,5-dihydroxyimidazolidin-2-ones by oxidation of imidazolin-2-ones with HNO3.
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Baranov, Vladimir V., Prakhov, Pavel D., Kolotyrkina, Natalya G., and Kravchenko, Angelina N.
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OXIDATION , *ACYLOINS - Abstract
[Display omitted] Previously unavailable 1,3-dialkyl-4,5-diaryl-4,5-dihydroxyimidazolidin-2-ones were obtained by the oxidation of 1,3-dialkyl-4,5-diaryl-4-imidazolin-2-ones with HNO3 (65 or 84% aq.). The scope of required 4-imidazolin-2-ones obtained from acyloins has been expanded, which provided preparation of new representatives of the title compounds. [ABSTRACT FROM AUTHOR]
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- 2024
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16. MANDRA-IDYLLIA MUNICIPALITY, TECHNICAL SERVICES DIRECTORATE invites tenders for Study for the Construction of a New High School of Erythro (Emergency Filodimos Ii)
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Diastereomers ,School construction ,News, opinion and commentary ,Erythro (Medication) - Abstract
MANDRA-IDYLLIA MUNICIPALITY, TECHNICAL SERVICES DIRECTORATE, Greece has invited tenders for Study for the Construction of a New High School of Erythro (Emergency Filodimos Ii). Tender Notice No: 208937 Deadline: September [...]
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- 2024
17. CVI BEST AKTIV COM SRL secures contract for Reagents And Contrast Media - Tenofovir-D6 Diphosphate Triethylamine Salt (Mixture Of Diastereomers)
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Diastereomers ,Chemical tests and reagents ,Tenofovir ,Contrast media ,Contract agreement ,News, opinion and commentary - Abstract
Romania based CVI BEST AKTIV COM SRL has secured contract from Institutul de Boli Infectioase Prof. Dr. Matei Bals for Reagents And Contrast Media - Tenofovir-D6 Diphosphate Triethylamine Salt (Mixture [...]
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- 2024
18. LABORATORIUM LIFE SCIENCE SRL secures contract for Reagents And Contrast Media - Tenofovir Alafenamide-D5 Fumarate (Diastereomers)
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Diastereomers ,Chemical tests and reagents ,Tenofovir ,Contrast media ,Contract agreement ,News, opinion and commentary - Abstract
Romania based LABORATORIUM LIFE SCIENCE SRL has secured contract from Institutul de Boli Infectioase Prof. Dr. Matei Bals for Reagents And Contrast Media - Tenofovir Alafenamide-D5 Fumarate (Diastereomers). The value [...]
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- 2024
19. BIO AQUA GROUP secures contract for Reagents And Contrast Media - Tenofovir Diphosphate Triethylamine Salt (Mixture Of Diastereomers) (Metabolit Active)
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Diastereomers ,Chemical tests and reagents ,Tenofovir ,Contrast media ,Contract agreement ,News, opinion and commentary - Abstract
Romania based BIO AQUA GROUP has secured contract from Institutul de Boli Infectioase Prof. Dr. Matei Bals for Reagents And Contrast Media - Tenofovir Diphosphate Triethylamine Salt (Mixture Of Diastereomers) [...]
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- 2024
20. Mass–Energy Profiles Obtained by Quantum Chemical Computing Applied in Mass Spectrometry: A Case Study with Identification of a Group of Acetalized Monosaccharide Isomers.
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Cojocariu, Carolina, Dinca, Nicolae, Georgescu, Marius, Sisu, Eugen, Serb, Alina, and Pascariu, Mihai-Cosmin
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MASS spectrometry ,ISOMERS ,QUANTUM computing ,STEREOCHEMISTRY ,IONS spectra ,DIASTEREOISOMERS - Abstract
Accurate modeling of small molecules substantially reduces the logistical effort and time consumption to discover and then obtain chemicals with various applications. Molecular stereochemistry is fundamentally involved in the intermolecular interactions that give rise to biological activity. Establishing the configuration of the asymmetric carbon in diastereomers can be decisive in drug design. In the presented analytical technique, on the basis of quantitative structure–fragmentation relationship (QSFR), mass–energy profiles obtained by electron ionization mass spectrometry (EI-MS) for analytes are used, along with some profiles for candidate structures calculated by quantum chemical (QC) methods. Our paper establishes the analytical conditions that lead to the best matching scores of such profiles corresponding to the actual structures for some isomers of acetalized monosaccharides. The optimization was achieved by group validation of five analytes, using four independent variables: the QC method, the descriptor of calculated energy, the impact energy of electrons, and the descriptor of experimental energy. The true structures were obtained using experimental profiles obtained at low electronic impact energies, and profiles were calculated using the DFT (B3LYP/6-31G) and RM1 QC methods. The double quantification of the ionic mass and the energy that generates it, for only a few primary ions of the mass spectrum, even allows the differentiation of acetalized diastereomers. [ABSTRACT FROM AUTHOR]
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- 2023
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21. Discovery of a Potent Highly Biased MOR Partial Agonist among Diastereomeric C9-Hydroxyalkyl-5-phenylmorphans.
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Lutz, Joshua A., Sulima, Agnieszka, Gutman, Eugene S., Bow, Eric W., Luo, Dan, Kaska, Sophia, Prisinzano, Thomas E., Paronis, Carol A., Bergman, Jack, Imler, Gregory H., Kerr, Andrew T., Jacobson, Arthur E., and Rice, Kenner C.
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STEREOCHEMISTRY , *DIASTEREOISOMERS , *FENTANYL , *LIPOPHILICITY , *PHENOL , *OPIOID receptors , *PHENOLS - Abstract
All possible diastereomeric C9-hydroxymethyl-, hydroxyethyl-, and hydroxypropyl-substituted 5-phenylmorphans were synthesized to explore the three-dimensional space around the C9 substituent in our search for potent MOR partial agonists. These compounds were designed to lessen the lipophilicity observed with their C9-alkenyl substituted relatives. Many of the 12 diastereomers that were obtained were found to have nanomolar or subnanomolar potency in the forskolin-induced cAMP accumulation assay. Almost all these potent compounds were fully efficacious, and three of those chosen for in vivo evaluation, 15, 21, and 36, were all extremely G-protein biased; none of the three compounds recruited beta-arrestin2. Only one of the 12 diastereomers, 21 (3-((1S,5R,9R)-9-(2-hydroxyethyl)-2-phenethyl-2-azabicyclo[3.3.1]nonan-5-yl)phenol), was a MOR partial agonist with good, but not full, efficacy (Emax = 85%) and subnanomolar potency (EC50 = 0.91 nM) in the cAMP assay. It did not have any KOR agonist activity. This compound was unlike morphine in that it had a limited ventilatory effect in vivo. The activity of 21 could be related to one or more of three well-known theories that attempt to predict a dissociation of the desired analgesia from the undesirable opioid-like side-effects associated with clinically used opioids. In accordance with the theories, 21 was a potent MOR partial agonist, it was highly G-protein biased and did not attract beta-arrestin2, and it was found to have both MOR and DOR agonist activity. All the other diastereomers that were synthesized were either much less potent than 21 or had either too little or too much efficacy for our purposes. It was also noted that a C9-methoxymethyl compound with 1R,5S,9R stereochemistry (41) was more potent than the comparable C9-hydroxymethyl compound 11 (EC50 = 0.65 nM for 41 vs. 2.05 nM for 11). Both 41 and 11 were fully efficacious. [ABSTRACT FROM AUTHOR]
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- 2023
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22. Impact of Non-Covalent Interactions of Chiral Linked Systems in Solution on Photoinduced Electron Transfer Efficiency.
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Magin, Ilya M., Pushkin, Ivan A., Ageeva, Aleksandra A., Martianova, Sofia O., Polyakov, Nikolay E., Doktorov, Alexander B., and Leshina, Tatyana V.
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PHOTOINDUCED electron transfer , *POLARIZATION (Nuclear physics) , *CHIRALITY of nuclear particles , *HETERODIMERS , *HOMODIMERS , *DIASTEREOISOMERS , *DIMERS - Abstract
It is well-known that non-covalent interactions play an essential role in the functioning of biomolecules in living organisms. The significant attention of researchers is focused on the mechanisms of associates formation and the role of the chiral configuration of proteins, peptides, and amino acids in the association. We have recently demonstrated the unique sensitivity of chemically induced dynamic nuclear polarization (CIDNP) formed in photoinduced electron transfer (PET) in chiral donor–acceptor dyads to non-covalent interactions of its diastereomers in solutions. The present study further develops the approach for quantitatively analyzing the factors that determine the association by examples of dimerization of the diastereomers with the RS, SR, and SS optical configurations. It has been shown that, under the UV irradiation of dyads, CIDNP is formed in associates, namely, homodimers (SS-SS), (SR-SR), and heterodimers (SS-SR) of diastereomers. In particular, the efficiency of PET in homo-, heterodimers, and monomers of dyads completely determines the forms of dependences of the CIDNP enhancement coefficient ratio of SS and RS, SR configurations on the ratio of diastereomer concentrations. We expect that the use of such a correlation can be useful in identifying small-sized associates in peptides, which is still a problem. [ABSTRACT FROM AUTHOR]
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- 2023
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23. An Insight into the Asymmetric Resolution of 1‐Aminoindane Derivatives.
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Akıncıoğlu, Akın, Akbaba, Yusuf, Polat Köse, Leyla, and Göksu, Süleyman
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MITSUNOBU reaction , *CENTRAL nervous system , *CHLORIDES - Abstract
Compounds with 1‐aminoindane motif exhibit vital biological activities in the central nervous system. Therefore, it is very important to synthesize new compounds with this moiety and to obtain them in high enantiopurity. In this study, novel substituted 1‐aminoindane derivatives were synthesized, and their asymmetric resolutions were carried out. Accordingly, the reduction of 1‐indanones with NaBH4, conversion of alcohols to azides via an alternative Mitsunobu reaction followed by reduction of azides afforded (±)‐1‐aminoindane hydrochloride or hydrobromide salts. Amine salts were converted into their free amines by using excess amount of Et3N and then in situ occurred free (±)‐amines were reacted with (R)‐O‐acetylmandeloyl chloride to give diastereomeric mixtures. The crystallization of the diastereomeric mixtures followed by hydrolysis yielded the corresponding asymmetric amines with high enantio‐purity. [ABSTRACT FROM AUTHOR]
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- 2023
- Full Text
- View/download PDF
24. Two new ent-kaurane-type diterpene diastereomers isolated from Coffea canephora.
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Nguyen, Thi Anh Tuyet, Hoang, Minh Hao, Luc, Thi Tuyen, Dang, Thi Kim Ngan, Nguyen, Thi My Tang, and Vo, Thi Nga
- Subjects
DIASTEREOISOMERS ,COFFEE ,AMINO acid residues ,BINDING energy - Abstract
Phytochemical investigation of the trunks of Coffea canephora yielded two new ent-kaurane diterpene diastereomers, which have been named coffecanepholide A, ent-3β,16β,17-trihydroxykauran-18-al (1) and coffecanepholide B, ent-3β,16β,17-trihydroxykauran-19-al (2). Structural elucidation and configurational assignment were deduced from extensive spectroscopic NMR/HRESIMS analysis and by comparison with the spectral data of the literature relevant structures. The isolated compounds were assayed for in vitro inhibitory activities against α-glucosidase. Structure 2 showed the α-glucosidase inhibitory activity with an IC
50 value of 294.7 ± 0.9 μM, while compound 1 exhibited inactivity. In addition, the docking results revealed that structure 2 can form more interactions with amino acid residues at the active site of α-glucosidase, which gave a more negative binding energy (−9.56 kcal/mol) compared with 1 (−8.60 kcal/mol). This observation might be responsible for a better activity of 2 against α-glucosidase. [ABSTRACT FROM AUTHOR]- Published
- 2023
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25. Diastereomeric multi‐chiral pendant groups: Their key role in stimuli‐responsive polymeric responses.
- Author
-
Rodríguez, Rafael, Rivadulla‐Cendal, Elena, Quiñoá, Emilio, and Freire, Félix
- Subjects
- *
CHIRAL centers , *HANDEDNESS , *DIASTEREOISOMERS , *POLYMERS - Abstract
Chiral information transmission in helical polymers bearing multi‐chiral pendant groups is usually determined by the absolute configuration of the first chiral center. The second chiral residue usually has low‐to‐null influence in the macromolecular handedness of the polymer, due to its remote position respect to the polyene main chain. Here, we demonstrate how the stimuli responsive properties of diastereomeric polymers, obtained by changing the absolute configuration of the second chiral center, are different due to the unlike properties of diastereoisomers. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
26. Synthesis and Characterization of the Diastereomers of HHC and H4CBD.
- Author
-
Collins, Arianna, Ramirez, Giovanni, Tesfatsion, Tesfay, Ray, Kyle P, Caudill, Scott, and Cruces, Westley
- Abstract
The characterization of any compound is important in the field of chemistry. As the field of cannabinoid chemistry grows so does the need for the characterization of new cannabinoids or rare cannabinoids that gain popularity within the consumer and research fields. Hexahydrocannabinol (HHC) a hydrogenated analogue of Δ9-tetrahydrocannabinol (THC), also found in trace amounts naturally within the Cannabis sativa plant, has been gaining attention and popularity within the cannabis industry. Hexahydrocannabidiol (H4CBD) is a synthetic hydrogenated analogue to cannabidiol (CBD). Identifying the diastereomers of the cannabinoids with instrumentation plays a huge role within the chemistry field adding valuable information of the structure and the parameters for others to identify such cannabinoids. Elucidation and characterization of HHC and H4CBD were performed using current analytical techniques such as 1D and 2D nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS), effectively characterizing both the diastereomers of HHC and H4CBD. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
27. Diastereomers of Spheroidal Form and Commercially Available Taxifolin Samples
- Author
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Roman P. Terekhov, Evgeny S. Melnikov, Ilya D. Nikitin, Margarita A. Tokareva, Tatyana A. Rodina, Anastasiya D. Savina, Denis I. Pankov, Anastasiya K. Zhevlakova, Vladimir L. Beloborodov, and Irina A. Selivanova
- Subjects
taxifolin ,flavonoid ,antioxidant ,diastereomers ,stereoisomers ,active pharmaceutical ingredient ,Pharmacy and materia medica ,RS1-441 - Abstract
Taxifolin is a natural polyphenol belonging to the class of flavonoids. The structure of this compound is characterized by the presence of two chiral centers. The spheroidal form of taxifolin (TAXs) has emerged as a promising modification due to enhanced solubility, higher safety profile, and long-term release from solid dosage forms. The study’s objective was to assess the diastereomeric content in TAXs and industrially produced samples of taxifolin. Considering the difference in the physico-chemical properties of diastereomers and based on the literature data, we developed a qualitative HPLC method. The chromatograms were recorded using a diode array detector at 290 nm and a mass spectrometer operated in negative ionization mode. Our data suggest that a biphenyl column and gradient elution using 0.1% formic acid in water and 0.2% formic acid in methanol, with the organic phase gradient from 7% to 21% and a flow rate of 0.65 mL/min for 15 min at 60 °C, provides the best conditions for the separation of taxifolin diastereomers. This method was validated for quantitative analysis. We discovered that the cis-isomer was present in all the analyzed samples, with its quantity ranging from 0.8% to 9.5%. TAXs can be considered a sample enriched with diastereomers.
- Published
- 2024
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28. Synthesis of Novel Phosphorus-Containing Derivatives of 1,3,4-Trimethylglycoluril via the Birum–Oleksyszyn Reaction
- Author
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Sergey I. Gorbin, Abdigali A. Bakibaev, Vera P. Tuguldurova, Andrey V. Kotov, Gleb O. Sysoev, Andrei S. Potapov, Dmitry I. Pavlov, Victor S. Malkov, Alexey S. Knyazev, Dmitriy A. Kurgachev, and Mark V. Michalchenkov
- Subjects
Birum–Oleksyszyn reaction ,1,3,4-trimethylglycoluril ,aryldiphenylphosphonates ,diastereomers ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
This work presents the synthesis of a new compound, 1-[aryl-(diphenylphosphono)methyl]-3,4,6-trimethylglycolurils, via the interaction of benzaldehyde and its mononitro- and monohydroxyderivatives with 1,3,4-trimethylglycoluril and triphenylphosphite. By varying the reaction conditions and the catalysts, the obtained product yields ranged from satisfactory to good. The diastereomers formed during the reaction were separated by semipreparative HPLC on the C18 stationary phase. The isolated diastereomers were characterized by 1H, 13C, and 31P NMR, and the structures of the diastereomers were confirmed using a single-crystal X-ray crystal structure analysis and quantum chemical calculations.
- Published
- 2023
- Full Text
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29. Drug testing for mitragynine and kratom: Analytical challenges and medico‐legal considerations.
- Author
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Helander, Anders and Rylski, Alexia
- Abstract
Mitragyna speciosa, known as kratom, is a tropical tree native to Southeast Asia that has long been used to increase energy and in traditional medicine. Kratom leaves contain several indole alkaloids including mitragynine, mitraciliatine, speciogynine, and speciociliatine, which have the same molecular formula and connectivity, but different spatial arrangements (i.e., diastereomers). A routine liquid‐chromatographic–high‐resolution mass‐spectrometric (LC‐HRMS) multi‐analyte method for addictive and herbal drugs in urine did not separate mitragynine from speciogynine and speciociliatine. Separation and individual measurement of the four diastereomers was possible with an improved LC method. All diastereomers were detected in 29 patient urine samples who tested positive for mitragynine with the routine method, albeit at variable absolute amounts and relative proportions. The presence of all diastereomers rather than individual substances indicated that they originated from the intake of kratom (i.e., plant material). Speciociliatine dominated in most samples (66%), whereas mitragynine and mitraciliatine were the highest in 17% each. A kratom product (powdered plant material) marketed in Sweden contained all diastereomers with mitragynine showing the highest level. In Sweden, there are signs of an increasing use of kratom in society, based on the results from drug testing, the number of poisons center consultations on intoxications, and customs seizure statistics. Because there may be health risks associated with kratom use, including dependence, serious adverse reactions, and death, analytical methods should be able to identify and quantify all diastereomers. In Sweden, this is important from a legal perspective, as only mitragynine is classified, whereas the other three diastereomers, and kratom (plant material), are not. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
30. Highly Conjugated Bis(benzo[b]phosphole)‐P‐oxides: Synthesis and Electrochemical, Optical, and Computational Studies.
- Author
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D'Imperio, Nicolas, Pelliccioli, Valentina, Grecchi, Sara, Bossi, Alberto, Vasile, Francesca, Cauteruccio, Silvia, Arkhypchuk, Anna I., Kumar Gupta, Arvind, Orthaber, Andreas, Ott, Sascha, and Licandro, Emanuela
- Subjects
- *
CARBON-carbon bonds , *DOUBLE bonds , *PHOSPHINE oxides , *ISOMERS , *OPTICAL properties , *ATOMS - Abstract
The first examples of a π‐conjugated benzo[b]phosphole P‐oxide in which two phosphole P‐oxide units are connected by a carbon‐carbon double bond are described. The molecules are synthesized as E isomers with respect to the carbon‐carbon double bond and exist as stable cis and trans isomers (chiral and meso one respectively) relatively to the two stereogenic P atoms. The optical and electrochemical properties of both isomers have been investigated by experiment and computations. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
31. Effect of relative configuration of TEMPO-type nitroxides on ascorbate reduction.
- Author
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Azuma, Risa, Yamasaki, Toshihide, Emoto, Miho C., Sato-Akaba, Hideo, Sano, Kohei, Munekane, Masayuki, Fujii, Hirotada G., and Mukai, Takahiro
- Subjects
- *
ELECTRON paramagnetic resonance , *NITROXIDES , *POLAR effects (Chemistry) - Abstract
2,2,6,6-Tetramethylpiperidin- N -oxyl (TEMPO)-type nitroxides are susceptible to bioreduction, leading to a loss of radical properties. Although it has been reported that the steric and electronic environments around the N–O moiety of nitroxides affect the reduction, how the relative configuration of nitroxide derivatives alters it is unclear. In this study, we investigated the effect of diastereomers on the radical properties of C2- and C4-disubstituted TEMPO-type nitroxides. We succeeded in isolating the diastereomers of the studied nitroxides for the first time. In addition, we compared the reactivities of nitroxide derivatives with different substituents at the C2 and C4 positions toward ascorbate reduction. We found that the bulky substituents at both C2 and C4 and the electronic effect of C4 affected the reduction of the isomers. C2- and C4-disubstituted nitroxides were administered to mice for electron spin resonance imaging to assess bioreduction in the brain. Similar to the reactivity to reduction in vitro , a difference in the bioreduction of diastereomers was observed in brain tissues. Our research strongly indicates that bioreduction can be controlled by changing the relative configuration, which can be used in the design of nitroxide derivatives for biological applications. [Display omitted] • The effect of diastereomers of TEMPO-type nitroxides was evaluated. • Diastereomers of C2- and C4-disubstituted TEMPO-type nitroxides were isolated. • Both bulky substituents on C2 and C4 affected reduction with ascorbate. • Similar to the in vitro results, the bioreduction reactivity also differed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
32. Synthesis and study of antiplatelet and antithrombotic activity of 4-substituted pyroglutamic acids.
- Author
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Vigorov, A. Yu., Nizova, I. A., Levit, G. L., Matveeva, T. V., Sadretdinova, L. Sh., Nazarov, O. I., Kovalev, N. S., Bakulin, D. A., Kurkin, D. V., Tyurenkov, I. N., and Krasnov, V. P.
- Subjects
- *
VENOUS thrombosis , *HYDROLYSIS , *ASPIRIN , *ACIDS - Abstract
A series of (2S,4S)-4-amino-N-arylpyroglutamic acids was first obtained by the nucleophilic substitution of bromine atom in dimethyl (2S,4RS)-4-bromo-N-phthaloylglutamate under the action of primary arylamines, followed by the separation of diastereomers and removal of protecting groups by acidic hydrolysis. These compounds were studied for anti-platelet and antithrombotic activity in experiments in vitro and in vivo. Some compounds were identified as exhibiting a significant effect on platelet function, which was manifested in slowing down the process of thrombus formation in the model of arterial and deep vein thrombosis. It was established that the most efficient compound is (2S,4S)-4-amino-N-(4-fluoro-phenyl)pyroglutamic acid, with its effect being comparable to that of acetylsalicylic acid. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
33. Screening of Novel Antimicrobial Diastereomers of Azithromycin–Thiosemicarbazone Conjugates: A Combined LC-SPE/Cryo NMR, MS/MS and Molecular Modeling Approach.
- Author
-
Habinovec, Iva, Mikulandra, Ivana, Pranjić, Paula, Kazazić, Saša, Paljetak, Hana Čipčić, Barišić, Antun, Bertoša, Branimir, Bukvić, Mirjana, and Novak, Predrag
- Subjects
DIASTEREOISOMERS ,RESPIRATORY infections ,DRUG resistance in bacteria ,MOLECULAR dynamics ,MACROLIDE antibiotics - Abstract
A well-known class of antibacterials, 14- and 15-membered macrolides are widely prescribed to treat upper and lower respiratory tract infections. Azithromycin is a 15-membered macrolide antibiotic possessing a broad spectrum of antibacterial potency and favorable pharmacokinetics. Bacterial resistance to marketed antibiotics is growing rapidly and represents one of the major global hazards to human health. Today, there is a high need for discovery of new anti-infective agents to combat resistance. Recently discovered conjugates of azithromycin and thiosemicarbazones, the macrozones, represent one such class that exhibits promising activities against resistant pathogens. In this paper, we employed an approach which combined LC-SPE/cryo NMR, MS/MS and molecular modeling for rapid separation, identification and characterization of bioactive macrozones and their diastereomers. Multitrapping of the chromatographic peaks on SPE cartridges enabled sufficient sample quantities for structure elucidation and biological testing. Furthermore, two-dimensional NOESY NMR data and molecular dynamics simulations revealed stereogenic centers with inversion of chirality. Differences in biological activities among diastereomers were detected. These results should be considered in the process of designing new macrolide compounds with bioactivity. We have shown that this methodology can be used for a fast screening and identification of the macrolide reaction components, including stereoisomers, which can serve as a source of new antibacterials. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
34. Economical and rapid enantioselective, diastereoselective and achiral separation of palonosetron hydrochloride and its impurities using supercritical fluid chromatography.
- Author
-
Qiu, Xiaodan, Liu, Yitong, Zhao, Xuejia, Lian, Xiaofang, Xing, Jianguo, Zheng, Ruifang, Yao, Jing, and Shan, Guangzhi
- Subjects
- *
SUPERCRITICAL fluid chromatography , *CHIRAL stationary phases , *GRADIENT elution (Chromatography) , *CHIRAL centers , *ISOMERS - Abstract
• Chiral/achiral separation of palonosetron and its impurities were achieved by SFC. • Enantio- and diastereo-selective separation of palonosetron were accomplished. • Ternary solvent mixture was crucial for the separation of four isomers. • The separation process was entropy driven. • H-bonding and π–π interactions were main interactions between CSP and analytes. Simultaneous separation of compounds with multiple chiral centers and highly similar structures presents significant challenges. This study developed a novel supercritical fluid chromatography (SFC) method with reduced organic solvent consumption and robust separation capabilities to address these challenges. The method was applied to simultaneously achieve enantioselective, diastereoselective, and achiral separation of palonosetron hydrochloride and its six impurities. The effects of the polysaccharide-based chiral stationary phase (CSP), modifier, additive, and column temperature on retention and separation were comprehensively evaluated. It was found that a combination of a polysaccharide-based CSP and a single modifier or a mixture of protonic modifiers could not achieve complete separation due to high structural similarity. However, an ADH column and a ternary solvent mixture containing acetonitrile (methanol: acetonitrile: diethylamine, 60:40:0.2, v/v/v) provided satisfying separation, particularly for the enantiomer and diastereomers of palonosetron. Using the optimized method, the enantioselective, diastereoselective, and achiral separation of palonosetron hydrochloride and its six impurities can be accomplished in 18 min under gradient elution. Thermodynamic results indicated that the separation process was entropy driven. A molecular docking study revealed that the separation was mainly achieved through the differences in hydrogen bond and π - π interactions between the analytes and CSP. This study lays the foundation for SFC analysis of palonosetron hydrochloride and provides a reference for the simultaneous SFC separation of the enantiomers, diastereoisomers and structurally similar compounds. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. HPLC with chiral stationary phase for separation and kinetics study of aspartic acid epimerization in Peroxiredoxin 2 active site peptide.
- Author
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Zhang, Xinran, Abdulbagi, Mohamed, Wang, Limin, Wang, Jiafeng, Di, Bin, and Li, Bo
- Subjects
- *
ASPARTIC acid , *PEPTIDES , *EPIMERIZATION , *CHIRAL stationary phases , *HIGH performance liquid chromatography , *FREE radical scavengers - Abstract
Amino acid epimerization, a process of converting L -amino acids to D -amino acids, will lead to modification in the protein structure and, subsequently, its biological function. This modification causes no change in protein m/z and may be overlooked during protein analysis. Aspartic Acid Epimerization (AAE) is faster than other amino acids and could be accelerated by free radicals and peroxides. In this work, a novel and site-specific HPLC method using a chiral stationary phase for determining the AAE in the active site model peptide (AP) of Peroxiredoxin 2 has been developed and validated. The developed method showed good linearity (1 – 200 μg/mL) and recoveries of the limit of quantification (LOQ), low, medium, and high concentrations were between 85% and 115%. The Kinetics of AAE in AP were studied using the developed method, and the results showed that when ascorbic acid and Cu2+ coexisted, the AP epimerized rapidly. The AAE extent increased with time and was positively correlated with hydrogen peroxide generation. • A novel HPLC method using a chiral column for the separation of Prx2 active site peptide (AP) epimers. • The method used for the kinetics study of aspartic acid epimerization in AP. • AP epimerized rapidly in ascorbic acid and Cu2+ system. • Epimerization increased with time and positively correlated with H 2 O 2 generated from this system. • Epimerization was terminated by adding a free radical scavenger indicating that H 2 O 2 played a vital role. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
36. Synthesis and separation of diastereomeric N‐(1‐phenylethyl)amides of inherently chiral hydroxydibenzoyloxy‐calix[4]arene acetic acids.
- Author
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Trybrat, Oleksandr O., Yesypenko, Oleksandr A., Rusanov, Eduard B., and Kalchenko, Vitaly I.
- Subjects
- *
ACETIC acid , *AMIDES , *X-ray diffraction - Abstract
A preparative method for the synthesis of optically pure N‐(1‐phenylethyl)amides of inherently chiral (cR)‐ and (cS)‐dibenzoyloxy‐calix[4]arene acetic acids has been developed. Their absolute stereochemical configuration was determined by X‐ray diffraction analysis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
37. Spectroscopic studies on the formation of different diastereomers in polyesters based on nadic acid.
- Author
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Kreuzer, Viktoria, Bretterbauer, Klaus, Buchinger, Gerhard, Kaiser, Lisa, Roiser, Lukas, and Schwarzinger, Clemens
- Subjects
- *
POLYESTERS , *DIASTEREOISOMERS , *MATRIX-assisted laser desorption-ionization , *GEL permeation chromatography , *GLASS transition temperature , *NUCLEAR magnetic resonance spectroscopy - Abstract
Nadic acid-based polyesters were prepared by polycondensation with different diols and different stoichiometry of the monomers. Due to the four stereocenters of the acid component, four diastereomers can form in the polyester. The use of different alcohols and influence on the formation of diastereomers in the polyester was investigated. Identification of the stereoisomers has been done with 1D and 2D NMR spectroscopy, which revealed an influence of the diol component on their formation. Further structural elucidation was done by MALDI mass spectrometry and size exclusion chromatography. Another big influence of the diols was found on the glass transition temperatures, which ranged from −30 °C to 40 °C. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
38. Total Syntheses of the Proposed Structure of Iriomoteolide-1a, -1b and Synthesis of Three Derivatives for Structural Studies.
- Author
-
Ghosh, Arun K. and Yuan, Hao
- Abstract
Iriomoteolide-1a and iriomoteolide-1b are very potent cytotoxic agents, isolated from marine dinoflagellates. We carried out the enantioselective syntheses of the proposed structures of these natural products. However, our analysis of the NMR spectra of the synthetic iriomoteolide-1a and the natural products revealed that the structures of iriomoteolide-1a and iriomoteolide-1b were assigned incorrectly. Based upon our detailed analysis of the spectral data of the synthetic iriomoteolide-1a and the natural products, we rationally designed three diastereomers of the proposed structure of 1 in an effort to assign the correct structures. The key steps of our syntheses of the proposed structures of iriomoteolides involved a highly diastereoselective ene reaction, a carbocupration that utilized a Gilman reagent, a Julia–Kocienski olefination to couple fragments, and Yamaguchi macrolactonization to form the target macrolactone. This synthetic route was then utilized to carry out syntheses of three diastereomers to the proposed structure of 1. These diastereomeric structures show close similarities to natural iriomoteolide-1a; however, there were differences in their spectral data. While natural iriomoteolides exhibited potent cytotoxicies, our preliminary biological evaluation of synthetic iriomoteolide-1a, iriomoteolide-1b, and all three synthetic derivatives did not show any appreciable cytotoxic properties. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
39. A High-Affinity 64 Cu-Labeled Ligand for PET Imaging of Hepsin: Design, Synthesis, and Characterization.
- Author
-
Park, Ji-Hun, Zhang, Xuran, Ha, Hyunsoo, Kim, Jung Young, Choi, Joon Young, Lee, Kyung-Han, Byun, Youngjoo, and Choe, Yearn Seong
- Subjects
- *
PHOTOAFFINITY labeling , *POSITRON emission tomography , *BINDING site assay , *PROSTATE tumors , *PROSTATE cancer - Abstract
Hepsin, a cell surface serine protease, is a potential biomarker for the detection of prostate cancer due to its high expression in prostate cancer but not in normal prostate. This study aimed to develop a radioligand for positron emission tomography (PET) imaging of hepsin. Six leucine–arginine (Leu–Arg) dipeptide derivatives (two diastereomers for each of three ligands) were synthesized and evaluated for their binding affinities and selectivity for hepsin. Based on the binding assay, a natCu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)-conjugated ligand (3B) was selected for the development of a PET radioligand. [64Cu]3B was synthesized by labeling the DOTA-conjugated compound 11B with [64Cu]CuCl2 at 80 °C for 20 min. The radioligand was evaluated for prostate cancer cell binding and PET imaging in a prostate tumor mouse model. The results demonstrated that [64Cu]3B exhibited high binding to LNCaP cells, intermediate binding to 22Rv1 cells, and low binding to PC3 cells. PET studies of [64Cu]3B in mice, implanted with 22Rv1 and PC3 cells on each flank, revealed that the radioligand uptake was high and persistent in the 22Rv1 tumors over time, whereas it was low in PC3 tumors. The results of this study suggest that [64Cu]3B is a promising PET radioligand for hepsin imaging. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
40. Diastereomers
- Author
-
Bada, Jeffrey, Gargaud, Muriel, editor, Irvine, William M., editor, Amils, Ricardo, editor, Claeys, Philippe, editor, Cleaves, Henderson James, editor, Gerin, Maryvonne, editor, Rouan, Daniel, editor, Spohn, Tilman, editor, Tirard, Stéphane, editor, and Viso, Michel, editor
- Published
- 2023
- Full Text
- View/download PDF
41. Germany : A fungus converts cellulose directly into a novel platform chemical
- Subjects
Cellulose ,Diastereomers ,Fungi ,Genetically modified organisms ,Business, international - Abstract
The fungus Talaromyces verruculosus can produce the chemical erythro-isocitric acid, which has received little attention on the market to date, directly from cheap plant waste and thus make it interesting [...]
- Published
- 2024
42. Mass–Energy Profiles Obtained by Quantum Chemical Computing Applied in Mass Spectrometry: A Case Study with Identification of a Group of Acetalized Monosaccharide Isomers
- Author
-
Carolina Cojocariu, Nicolae Dinca, Marius Georgescu, Eugen Sisu, Alina Serb, and Mihai-Cosmin Pascariu
- Subjects
mass–energy profiles ,mass spectrometry (MS) ,quantitative structure–fragmentation relationship (QSFR) ,molecule recognition ,diastereomers ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Accurate modeling of small molecules substantially reduces the logistical effort and time consumption to discover and then obtain chemicals with various applications. Molecular stereochemistry is fundamentally involved in the intermolecular interactions that give rise to biological activity. Establishing the configuration of the asymmetric carbon in diastereomers can be decisive in drug design. In the presented analytical technique, on the basis of quantitative structure–fragmentation relationship (QSFR), mass–energy profiles obtained by electron ionization mass spectrometry (EI-MS) for analytes are used, along with some profiles for candidate structures calculated by quantum chemical (QC) methods. Our paper establishes the analytical conditions that lead to the best matching scores of such profiles corresponding to the actual structures for some isomers of acetalized monosaccharides. The optimization was achieved by group validation of five analytes, using four independent variables: the QC method, the descriptor of calculated energy, the impact energy of electrons, and the descriptor of experimental energy. The true structures were obtained using experimental profiles obtained at low electronic impact energies, and profiles were calculated using the DFT (B3LYP/6-31G) and RM1 QC methods. The double quantification of the ionic mass and the energy that generates it, for only a few primary ions of the mass spectrum, even allows the differentiation of acetalized diastereomers.
- Published
- 2023
- Full Text
- View/download PDF
43. Discovery of a Potent Highly Biased MOR Partial Agonist among Diastereomeric C9-Hydroxyalkyl-5-phenylmorphans
- Author
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Joshua A. Lutz, Agnieszka Sulima, Eugene S. Gutman, Eric W. Bow, Dan Luo, Sophia Kaska, Thomas E. Prisinzano, Carol A. Paronis, Jack Bergman, Gregory H. Imler, Andrew T. Kerr, Arthur E. Jacobson, and Kenner C. Rice
- Subjects
diastereomers ,C9-hydroxyalkyl 5-phenylmorphans ,m-hydroxy-N-phenethyl-5-phenylmorphans ,N-phenethyl-2-azabicyclo[3.3.1]nonan-5-yl)phenols ,mu-opioid receptor (MOR) ,delta-opioid receptor (DOR) ,Organic chemistry ,QD241-441 - Abstract
All possible diastereomeric C9-hydroxymethyl-, hydroxyethyl-, and hydroxypropyl-substituted 5-phenylmorphans were synthesized to explore the three-dimensional space around the C9 substituent in our search for potent MOR partial agonists. These compounds were designed to lessen the lipophilicity observed with their C9-alkenyl substituted relatives. Many of the 12 diastereomers that were obtained were found to have nanomolar or subnanomolar potency in the forskolin-induced cAMP accumulation assay. Almost all these potent compounds were fully efficacious, and three of those chosen for in vivo evaluation, 15, 21, and 36, were all extremely G-protein biased; none of the three compounds recruited beta-arrestin2. Only one of the 12 diastereomers, 21 (3-((1S,5R,9R)-9-(2-hydroxyethyl)-2-phenethyl-2-azabicyclo[3.3.1]nonan-5-yl)phenol), was a MOR partial agonist with good, but not full, efficacy (Emax = 85%) and subnanomolar potency (EC50 = 0.91 nM) in the cAMP assay. It did not have any KOR agonist activity. This compound was unlike morphine in that it had a limited ventilatory effect in vivo. The activity of 21 could be related to one or more of three well-known theories that attempt to predict a dissociation of the desired analgesia from the undesirable opioid-like side-effects associated with clinically used opioids. In accordance with the theories, 21 was a potent MOR partial agonist, it was highly G-protein biased and did not attract beta-arrestin2, and it was found to have both MOR and DOR agonist activity. All the other diastereomers that were synthesized were either much less potent than 21 or had either too little or too much efficacy for our purposes. It was also noted that a C9-methoxymethyl compound with 1R,5S,9R stereochemistry (41) was more potent than the comparable C9-hydroxymethyl compound 11 (EC50 = 0.65 nM for 41 vs. 2.05 nM for 11). Both 41 and 11 were fully efficacious.
- Published
- 2023
- Full Text
- View/download PDF
44. R-(+)- Limonene Diastereoselective Epoxidation: A Minireview About of the Synthesis Methods.
- Author
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Rubio Rodríguez, J. A. and Cubillos Lobo, J. A.
- Subjects
- *
EPOXIDATION , *ASYMMETRIC synthesis , *CHEMICAL amplification , *CATALYTIC oxidation , *LIMONENE , *INDUSTRIAL capacity , *METAL catalysts , *DIELS-Alder reaction - Abstract
R-(+)-limonene epoxidation has been focused from different synthesis methods. Thanks to the optically active epoxides obtained from this reaction are widely employed at industrial level, like: agrochemicals, polymers, cosmetics, pharmaceuticals. A key point found in this topic has been the asymmetric induction to improve the yield to the diastereomers of 1,2-limonene oxide. Many catalysts have been developed for the diastereoselective epoxidation, but some oxidation methodology have not been so useful. The enzymes and the Jacobsen's catalyst presented the highest selectivity towards the endocyclic epoxides diastereomers, while other catalysts like metals supported on mesoporous materials were directed to one or more oxidation products, reducing their potential industrial scaling. Also, it was evidenced that controlling the reaction parameters it allows the segregation homogeneous catalyst to a phase different from the reaction products, thus increasing its useful reutilization in several reaction cycles. This minireview confronts the different systems used for the diastereoselective epoxidation of R-(+)-limonene. Challenges, issues and trends of said chemical transformation are also discussed. [ABSTRACT FROM AUTHOR]
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- 2022
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45. Highly sensitive LC‐MS method for stereochemical quality control of a pharmaceutical drug substance intermediate.
- Author
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Wang, Lin, Tong, Weidong, Antonucci, Vincent, Helmy, Roy, and Truong, Van
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QUALITY control , *DRUGS , *LIQUID chromatography-mass spectrometry , *ENANTIOMERS , *DIASTEREOISOMERS , *STEREOISOMERS - Abstract
Stereochemical quality control for pharmaceutical drug substance intermediates is a daunting task, especially considering the need to separate multiple stereoisomers simultaneously with low ppm level sensitivity. To address these challenges, we have successfully implemented chiral column screening, and developed an ultrasensitive liquid chromatography–mass spectrometry (LC‐MS) method to separate four stereoisomers including the API intermediate, its enantiomer, and two other diastereomers. Parameters such as mobile phase additives, MS fragmentor, and column temperature were optimized to achieve the desired selectivity and sensitivity. The method enabled stereoisomer detection with high sensitivity (2 ppm LOD and 5 ppm LOQ), good linearity, and desired spike recovery, and it has been successfully applied for stereoisomer quantitation in multiple large‐scale batches and demonstrated chiral quality control of the drug substance intermediate. [ABSTRACT FROM AUTHOR]
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- 2022
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46. Development and Validation of a New Stereoselective RP-HPLC Method for Simultaneous Quantification of Tadalafil, its One Enantiomer, and Two Diastereomers in API and Tablet Form.
- Author
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Mhaske, Deepak Krishna and Kumbhar, Arjun Shankar
- Subjects
DIASTEREOISOMERS ,TADALAFIL ,HIGH performance liquid chromatography ,ENANTIOMERS ,ACETIC acid ,ISOMERS - Abstract
A new, simple, and stereoselective RP-HPLC method was developed and validated for the simultaneous quantification of tadalafil, its one enantiomer, and two diastereomers in API and tablets. Using varied compositions of water, acetonitrile, and acetic acid as mobile phases in gradient mode at a 0.40 mL/min flow rate and detection at 285 nm, all this separation was achieved on the Lux Cellulose-3 (150 mm x 4.6 mm, 3 µm) column at a 30.0°C oven temperature. All isomers were eluted within 24 minutes, with a resolution of more than 2.3 between any two isomers. With 10.0 µL injection volume, the LOD and LOQ were determined to be 0.06 µg/mL and 0.10 µg/mL, respectively. The linearity of tadalafil (0.10-400 µg/mL), one enantiomer, and two diastereomers (0.10-4.0 µg/mL) was confirmed with a correlation coefficient of 0.999. The forced degradation study revealed the specificity for all the peaks as well as the conversion of tadalafil into diastereomers (6S, 12aR) in acidic conditions and into diastereomers (6R, 12aS) in alkaline conditions. At lower concentrations, the recoveries for all isomers ranged from 100.0 ± 15.0%, while the assay values for tadalafil were within 100.0 ± 2.0%. According to the validation outcome as per ICH guidelines, the proposed method is an accurate, precise, linear, and robust stereoselective method for simultaneous quantification. [ABSTRACT FROM AUTHOR]
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- 2022
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47. Impact of Non-Covalent Interactions of Chiral Linked Systems in Solution on Photoinduced Electron Transfer Efficiency
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Ilya M. Magin, Ivan A. Pushkin, Aleksandra A. Ageeva, Sofia O. Martianova, Nikolay E. Polyakov, Alexander B. Doktorov, and Tatyana V. Leshina
- Subjects
non-covalent interactions ,photoinduced electron transfer (PET) ,chiral associates ,diastereomers ,chemically induced dynamic nuclear polarization (CIDNP) ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
It is well-known that non-covalent interactions play an essential role in the functioning of biomolecules in living organisms. The significant attention of researchers is focused on the mechanisms of associates formation and the role of the chiral configuration of proteins, peptides, and amino acids in the association. We have recently demonstrated the unique sensitivity of chemically induced dynamic nuclear polarization (CIDNP) formed in photoinduced electron transfer (PET) in chiral donor–acceptor dyads to non-covalent interactions of its diastereomers in solutions. The present study further develops the approach for quantitatively analyzing the factors that determine the association by examples of dimerization of the diastereomers with the RS, SR, and SS optical configurations. It has been shown that, under the UV irradiation of dyads, CIDNP is formed in associates, namely, homodimers (SS-SS), (SR-SR), and heterodimers (SS-SR) of diastereomers. In particular, the efficiency of PET in homo-, heterodimers, and monomers of dyads completely determines the forms of dependences of the CIDNP enhancement coefficient ratio of SS and RS, SR configurations on the ratio of diastereomer concentrations. We expect that the use of such a correlation can be useful in identifying small-sized associates in peptides, which is still a problem.
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- 2023
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48. Synthesis of substituted hexahydro-2H-chromeno[4,3-d]pyrimidine-2,5-diones and their modification at the hydroxy group.
- Author
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Makarova, E. S., Kabanova, M. V., Filimonov, S. I., Shetnev, A. A., and Suponitsky, K. Yu.
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ACYLATION - Abstract
We proposed an approach for the preparation of substituted hexahydro-2H-chromeno-[4,3-d]pyrimidine-2,5-diones and studied their selective acylation and alkylation at the hydroxy group on the example of (4R*,4aS*,10bR*)-diastereomers. [ABSTRACT FROM AUTHOR]
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- 2022
- Full Text
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49. Spectroscopic investigation of the different complexation and extraction properties of diastereomeric diglycolamide ligands.
- Author
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Weßling, Patrik, Trumm, Michael, Sittel, Thomas, Geist, Andreas, and Panak, Petra J.
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SOLVENT extraction ,STABILITY constants ,REACTOR fuel reprocessing ,TIME-resolved spectroscopy ,NUCLEAR fuels - Abstract
In comparison, the log I i ' SB 3 sb values for the complexation with I cis i -mTDDGA are 1.1 (for Cm(III)) and 1.8 (for Eu(III)) orders of magnitude higher than for the complexation with I trans i -mTDDGA, confirming I cis i -mTDDGA to be the stronger ligand. In contrast to the complexation of Cm(III) with I cis i - and I trans i -mTDDGA no spectroscopic evidence for a 1:2 complex with I cis i - or I trans i -mTDDGA with Eu(III) could be found. 2.2 Preparation of monophasic samples For monophasic experiments in dependence of the ligand concentration 4.5 mg I cis i -mTDDGA or 118.2 mg I trans i -mTDDGA were dissolved in 2 mL ( I cis i -mTDDGA) or 1 mL ( I trans i -mTDDGA) of 2-propanol with 5 vol% H SB 2 sb O and 1 × 10 SP -2 sp mol L SP -1 sp HClO SB 4 sb . 3 Results and discussion 3.1 Complexation of Cm(III) with cis - and trans -mTDDGA 3.1.1 cis -mTDDGA The complexation of Cm(III) with I cis i -mTDDGA was studied in 2-propanol with 5 vol% H SB 2 sb O and 1 × 10 SP -2 sp mol L SP -1 sp HClO SB 4 sb . [Extracted from the article]
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- 2022
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50. Chiral Linked Systems as a Model for Understanding D-Amino Acids Influence on the Structure and Properties of Amyloid Peptides.
- Author
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Ageeva, Aleksandra A., Doktorov, Alexander B., Polyakov, Nikolay E., and Leshina, Tatyana V.
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PEPTIDES , *PHOTOINDUCED electron transfer , *ALZHEIMER'S disease , *ISOMERS - Abstract
In this review, we provide an illustration of the idea discussed in the literature of using model compounds to study the effect of substitution of L- for D-amino acid residues in amyloid peptides. The need for modeling is due to the inability to study highly disordered peptides by traditional methods (high-field NMR, X-ray). At the same time, the appearance of such peptides, where L-amino acids are partially replaced by D-analogs is one of the main causes of Alzheimer's disease. The review presents examples of the use diastereomers with L-/D-tryptophan in model process—photoinduced electron transfer (ET) for studying differences in reactivity and structure of systems with L- and D-optical isomers. The combined application of spin effects, including those calculated using the original theory, fluorescence techniques and molecular modeling has demonstrated a real difference in the structure and efficiency of ET in diastereomers with L-/D-tryptophan residues. In addition, the review compared the factors governing chiral inversion in model metallopeptides and Aβ42 amyloid. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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