Synthesis and structural elucidation of a phthalide analog using NMR analysis and DFT calculations

Pinto, Bryan Nickson Santana; Teixeira, Milena Galdino; Alvarenga, Elson S.

doi:10.1002/mrc.4976

Cited by 5 publications

(8 citation statements)

References 24 publications

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“…So far NMR has successfully identified novel molecules in multiple FBDD drug discovery experiments (39)(40)(41)(42)(43)(44). NMR can also be used in chemistry for the structural elucidation of a molecule (45)(46)(47). NMR can even be used in quality assessment for the food industry (48,49) and petroleum industry (50,51).…”

Section: The Application Of Nmr To Metabonomicsmentioning

confidence: 99%

1H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids?

2021

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While psychedelics may have therapeutic potential for treating mental health disorders such as depression, further research is needed to better understand their biological effects and mechanisms of action when considering the development of future novel therapy approaches. Psychedelic research could potentially benefit from the integration of metabonomics by proton nuclear magnetic resonance (1H NMR) spectroscopy which is an analytical chemistry-based approach that can measure the breakdown of drugs into their metabolites and their metabolic consequences from various biofluids. We have performed a systematic review with the primary aim of exploring published literature where 1H NMR analysed psychedelic substances including psilocin, lysergic acid diethylamide (LSD), LSD derivatives, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and bufotenin. The second aim was to assess the benefits and limitations of 1H NMR spectroscopy-based metabolomics as a tool in psychedelic research and the final aim was to explore potential future directions. We found that the most current use of 1H NMR in psychedelic research has been for the structural elucidation and analytical characterisation of psychedelic molecules and that no papers used 1H NMR in the metabolic profiling of biofluids, thus exposing a current research gap and the underuse of 1H NMR. The efficacy of 1H NMR spectroscopy was also compared to mass spectrometry, where both metabonomics techniques have previously shown to be appropriate for biofluid analysis in other applications. Additionally, potential future directions for psychedelic research were identified as real-time NMR, in vivo1H nuclear magnetic resonance spectroscopy (MRS) and 1H NMR studies of the gut microbiome. Further psychedelic studies need to be conducted that incorporate the use of 1H NMR spectroscopy in the analysis of metabolites both in the peripheral biofluids and in vivo to determine whether it will be an effective future approach for clinical and naturalistic research.

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Section: The Application Of Nmr To Metabonomicsmentioning

confidence: 99%

1H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids?

2021

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“…29 A strategy that has gained prominence recently is the use of calculations based on quantum mechanics to simulate 1 H and 13 C NMR spectra. 24,25,[30][31][32] This is also driven by the growing computational power and user-friendly graphical interface software, that does not require expertise in programming languages. 33,34 Distinctive approaches can be used to calculate shielding tensors.…”

Section: Introductionmentioning

confidence: 99%

Deciphering molecular structures: NMR spectroscopy and quantum mechanical insights of halogenated 4H‐Chromenediones

Martins,

Souto,

Hoye

et al. 2024

Magnetic Reson in Chemistry

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Sesquiterpene lactones (SL) represent a class of secondary metabolites found in the Asteraceae family, notable for their unique structures. The SL α‐santonin (1) and its derivatives are worthy of mention due to their diverse biological properties. Additionally, 4H‐chromenes and 4H‐chromones are appealing frameworks holding the capability to be used as structural motifs for new drugs. Furthermore, unambiguous structural elucidation is crucial for developing novel compounds for diverse applications. In this context, it is common to find in the literature molecules erroneously assigned. Therefore, the use of quantum mechanical calculations to simulate NMR chemical shifts has emerged as a valuable strategy. In this work, we conceived the synthesis of two halogenated 4H‐chromenediones derived from photosantonic acid (2), a photoproduct arising from irradiation of α‐santonin (1) in the ultraviolet region. The structure of the chlorinated and brominated products was determined by NMR analysis, with the aid of quantum mechanical calculations at the B3LYP/6‐311 + G(2d,p)//M062x/6‐31 + G(d,p) level of theory. All analyses were in agreement and led to the assignment of the brominated 4H‐chromene‐2,7‐dione as (3S,3aS,5aR,9bS)‐5a‐(2‐bromopropan‐2‐yl)‐3‐methyl‐3,3a,5,5a,8,9b‐hexahydro‐4H‐furo[2,3‐f]chromene‐2,7‐dione (11b) and of the chlorinated 4H‐chromene‐2,7‐dione as (3S,3aS,5aR,9bS)‐5a‐(2‐chloropropan‐2‐yl)‐3‐methyl‐3,3a,5,5a,8,9b‐hexahydro‐4H‐furo[2,3‐f]chromene‐2,7‐dione (12b). The diastereoselectivities of the reactions were explained based on products and intermediates formation energy calculated using B3LYP/6‐31 + G(d,p) as the level of theory. Structures 11b and 12b were identified as the thermodynamic and kinetic products of the reaction among all candidates. Consequently, the strategy utilized in this study is robust and successfully illustrates the use of quantum mechanical calculations in the structural elucidation of new compounds with potential applications as novel drugs or products.

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“…A typical implementation that combines experimental NMR data and theoretical quantum mechanics calculation is common in the stereo structural assignment of a new molecule [31] …”

Section: Introductionmentioning

confidence: 99%

“…[30] A typical implementation that combines experimental NMR data and theoretical quantum mechanics calculation is common in the stereo structural assignment of a new molecule. [31] As each stereoisomer has intrinsic 1 H and 13 C chemical shifts, the theoretical NMR data of a set of candidate structures can be compared with the experimental NMR values of the new molecule. [32] Using specific quantitative parameters such as, mean absolute error (MAE) and linear fit (R 2 ) or statistical parameters like DP4 [33] and CP3, [34] it is possible to point out the NMR data of the candidate structure that best fit the experimental NMR data, thus elucidating the correct structure for the new natural product.…”

Section: Introductionmentioning

confidence: 99%

Structural Elucidation by NMR Analysis Assisted by DFT Calculations of a Novel Natural Product from Conchocarpus Mastigophorus (Rutaceae)

et al. 2022

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The stem of Conchocarpus mastigophorus was solvent-extracted and purified by silica-gel column chromatography to afford eleven natural products, including one new compound. The structures of all compounds were fully elucidated by spectrometric methods. NMR analyses assisted by theoretical calculations were used to determine the structure of a novel natural product. The structure of the novel compound 2 (acridone alkaloid) was established as 1,3,6-trihydroxy-2,4,5-trimethoxy-10-methylacridin-9(10H)-one. The absolute configuration of compound 1 was assigned by means of vibrational circular dichroism (VCD) spectroscopy. The structure of compound 1 was defined as (3S)-(À )-3-hydroxy-1-methylpiperidin-2-one. Theoretical calculations were performed at the B3LYP/6-311 + G(2d,p)//M06-2X/6-31 + G(d,p) level of theory and DP4 statistical tool was employed to compare the calculated and experimental NMR chemical shifts.

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Synthesis and structural elucidation of a phthalide analog using NMR analysis and DFT calculations

Cited by 5 publications

References 24 publications

1H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids?

1H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids?

Deciphering molecular structures: NMR spectroscopy and quantum mechanical insights of halogenated 4H‐Chromenediones

Structural Elucidation by NMR Analysis Assisted by DFT Calculations of a Novel Natural Product from Conchocarpus Mastigophorus (Rutaceae)

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