Application of modern NMR techniques for conformation analysis and assignment of NMR parameters of biologically active compounds (original) (raw)
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Chemistry & Biodiversity, 2005
Introduction. ± Modern spectroscopic methods have largely revolutionized compound identification and tremendously accelerated the pace at which isolated compounds can be identified nowadays. It is hard to believe that 50 years ago compounds still required tedious decomposition into known fragments, or, alternatively, total chemical synthesis to corroborate the proposed structures. However, when compound quantities are very small, total chemical synthesis for independent structure elucidation is still being performed in important cases.
Structure elucidation of bioactive molecules by applying modern NMR techniques
2005
I. Preliminaries and the aim of the thesis The subject of this thesis is the structural study of biologically active compounds, proline derivatives, flavonones and benzofuranones. My dissertation was based on the work executed by me as a member of a team. The organic molecules presented in chapters "Investigations on the prolyl-endopeptidase (PEP) inhibitors by NMR techniques" and "Analysis of 3(2H)-benzofuranone derivatives with NMR methods" were prepared in Chinoin Pharmaceutical and Chemical Works Ltd. under supervision of Dr. Sándor Bátori, Dr. Ágnes Horváth and Dr. Károly Kánai. Organic molecules referred to in chapter "Configuration and structure elucidation of 3-substituted flavanone derivatives with NMR methods" were synthesized by myself at the Department of Organic Chemistry of Debrecen Kossuth Lajos University under supervision of Dr. György Litkei and Prof. Dr. Sándor Antus. During the structural study of these compounds my aim was to gain detailed data including the relative configuration and conformation of molecules investigated. This information broadened our understanding the mechanisms of the formation of the compounds.
NMReDATA, a standard to report the NMR assignment and parameters of organic compounds
Magnetic resonance in chemistry : MRC, 2018
Even though NMR has found countless applications in the field of small molecule characterization, there is no standard file format available for the NMR data relevant to structure characterization of small molecules. A new format is therefore introduced to associate the NMR parameters extracted from 1D and 2D spectra of organic compounds to the proposed chemical structure. These NMR parameters, which we shall call NMReDATA (for nuclear magnetic resonance extracted data), include chemical shift values, signal integrals, intensities, multiplicities, scalar coupling constants, lists of 2D correlations, relaxation times and diffusion rates. The file format is an extension of the existing SDF (Structure Data Format), which is compatible with the commonly used MOL format. The association of an NMReDATA file with the raw and spectral data from which it originates constitutes an NMR record. This format is easily readable by humans and computers and provides a simple and efficient way for di...
Identification and structure elucidation by NMR spectroscopy
TrAC Trends in Analytical Chemistry, 2015
The state of the art and recent developments in application of nuclear magnetic resonance (NMR) for structure elucidation and identification of small organic molecules are discussed. The recently suggested new two-dimensional (2D)-NMR experiments combined with the advanced instrumentation allow structure elucidation of new organic compounds at a sample amount of less than 10 μg. A pure shift approach that provides 1 H-decoupled proton spectra drastically simplified 1 H and 2D NMR spectra interpretation. The structure elucidation of extremely hydrogen-deficient compounds was dramatically facilitated due to the methodology based on combination of new 2D-NMR experiments providing longrange heteronuclear correlations with computer-assisted structure elucidation (CASE). The capabilities of CASE systems are discussed. The role of NMR-spectrum prediction in structure verification and NMR approaches for qualitative mixture analysis are considered.
Essential Practical Nmr For Organic Chemistry
This book describes the use of NMR spectroscopy for dealing with problems of small organic molecule structural elucidation. It features a significant amount of vital chemical shift and coupling information but more importantly, it presents sound principles for the selection of the techniques relevant to the solving of particular types of problem, whilst stressing the importance of extracting the maximum available information from the simple 1-D proton experiment and of using this to plan subsequent experiments.
Essential parameters for structural analysis and dereplication by 1H NMR spectroscopy
2014
The present study demonstrates the importance of adequate precision when reporting the δ and J parameters of frequency domain 1 H NMR (HNMR) data. Using a variety of structural classes (terpenoids, phenolics, alkaloids) from different taxa (plants, cyanobacteria), this study develops rationales that explain the importance of enhanced precision in NMR spectroscopic analysis and rationalizes the need for reporting Δδ and ΔJ values at the 0.1−1 ppb and 10 mHz level, respectively. Spectral simulations paired with iteration are shown to be essential tools for complete spectral interpretation, adequate precision, and unambiguous HNMR-driven dereplication and metabolomic analysis. The broader applicability of the recommendation relates to the physicochemical properties of hydrogen (1 H) and its ubiquity in organic molecules, making HNMR spectra an integral component of structure elucidation and verification. Regardless of origin or molecular weight, the HNMR spectrum of a compound can be very complex and encode a wealth of structural information that is often obscured by limited spectral dispersion and the occurrence of higher order effects. This altogether limits spectral interpretation, confines decoding of the underlying spin parameters, and explains the major challenge associated with the translation of HNMR spectra into tabulated information. On the other hand, the reproducibility of the spectral data set of any (new) chemical entity is essential for its structure elucidation and subsequent dereplication. Handling and documenting HNMR data with adequate precision is critical for establishing unequivocal links between chemical structure, analytical data, metabolomes, and biological activity. Using the full potential of HNMR spectra will facilitate the general reproducibility for future studies of bioactive chemicals, especially of compounds obtained from the diversity of terrestrial and marine organisms.
P A R T I FUNDAMENTALS AND TECHNIQUES PRINCIPLES IN NMR SPECTROSCOPY
More than any other analytical method the nuclear magnetic resonance (NMR) spectroscopy provides information about the chemical structure and the dynamics of organic 3 molecules. The interpretation of the NMR data depends on a minimum amount of basic information that will be provided in this chapter. For a better appliance, these basics of oneand two-dimensional NMR techniques are demonstrated by means of practical examples. 0 2 J ° = 8.5 Hz J ° = 11.5 Hz J ° = 14.5 Hz J 180 = 15.5 Hz J 180 = 12.5 Hz J 180 = 9.5 Hz 4