Nuclear magnetic resonance structural elucidation

Cotterill P J, Scheinmann F, Stenhouse I A 1978 Extractives from Guttiferae. Part 34. Kolaflava-none, a new biflavanone from the nuts of Garcinia kola Heckel. Applications of 13-C nuclear magnetic resonance in elucidation of the structures of flavonoids. J Chem Soc Perkin Trans I 532-539... 

Other methods of identification include the customary preparation of derivatives, comparisons with authentic substances whenever possible, and periodate oxidation. Lately, the application of nuclear magnetic resonance spectroscopy has provided an elegant approach to the elucidation of structures and stereochemistry of various deoxy sugars (18). Microcell techniques can provide a spectrum on 5-6 mg. of sample. The practicing chemist is frequently confronted with the problem of having on hand a few milligrams of a product whose structure is unknown. It is especially in such instances that a full appreciation of the functions of mass spectrometry can be developed. 

NMR, nuclear magnetic resonance, is an analytical technique based on the energy differences of nuclear spin systems in a strong magnetic field. It is a powerful technique for structural elucidation of complex molecules. 

Other spectroscopic properties such as nuclear magnetic resonance (NMR), mass spectrometry (MS), infra-red (IR), and circular dichroism (CD) spectra of chlorophyll compounds and derivatives have been valuable tools for structural elucidation. - ... 

The development and reports of methods for colorless chlorophyll derivative (RCCs, FCCs, and NCCs) analysis are relatively recent and the structures of the compounds are being elucidated by deduction from their chromatographic behaviors, spectral characteristics (UV-Vis absorbance spectra), mass spectrometry, and nuclear magnetic resonance analysis. The main obstacle is that these compounds do not accumulate in appreciable quantities in situ and, moreover, there are no standards for them. The determination of the enzymatic activities of red chlorophyll catabolite reductase (RCCR) and pheophorbide a monoxygenase (PAO) also helps to monitor the appearance of colorless derivatives since they are the key enzymes responsible for the loss of green color. ... 

Hentschel, P. et ah. Structure elucidation of deoxylutein 11 isomers by on-line capillary high performance liquid chromatography- H nuclear magnetic resonance spectroscopy, J. Chromatogr. A, 1112, 285, 2006. 

Giusti, M.M., Ghanadan, H., and Wrolstad, R.E., Elucidation of the structure and conformation of red radish Raphanus sativus) anthocyanins using one- and two-dimensional nuclear magnetic resonance techniques, J. Agric. Food Chem., 46, 4858, 1998. 

Nuclear magnetic resonance (NMR) spectroscopy is, next to X-ray diffraction, the most important method to elucidate molecular structures of small molecules up to large bio macromolecules. It is used as a routine method in every chemical laboratory and it is not the aim of this article to give a comprehensive review about NMR in structural analysis. We will concentrate here on liquid-state applications with respect to drugs or drug-like molecules to emphasize techniques for conformational analysis including recent developments in the field. 

Several modem analytical instruments are powerful tools for the characterisation of end groups. Molecular spectroscopic techniques are commonly employed for this purpose. Nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy and mass spectrometry (MS), often in combination, can be used to elucidate the end group structures for many polymer systems more traditional chemical methods, such as titration, are still in wide use, but employed more for specific applications, for example, determining acid end group levels. Nowadays, NMR spectroscopy is usually the first technique employed, providing the polymer system is soluble in organic solvents, as quantification of the levels of... 

Nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research has been used primarily in a classical, organic chemistry framework. Typical studies have included (1) the structure elucidation of compounds [1,2], (2) investigating chirality of drug substances [3,4], (3) the determination of cellular metabolism [5,6], and (4) protein studies [7-9], to name but a few. From the development perspective, NMR is traditionally used again for structure elucidation, but also for analytical applications [10]. In each case, solution-phase NMR has been utilized. It seems ironic that although —90% of the pharmaceutical products on the market exist in the solid form, solid state NMR is in its infancy as applied to pharmaceutical problem solving and methods development. 

Modern spectroscopy plays an important role in pharmaceutical analysis. Historically, spectroscopic techniques such as infrared (IR), nuclear magnetic resonance (NMR), and mass spectrometry (MS) were used primarily for characterization of drug substances and structure elucidation of synthetic impurities and degradation products. Because of the limitation in specificity (spectral and chemical interference) and sensitivity, spectroscopy alone has assumed a much less important role than chromatographic techniques in quantitative analytical applications. However, spectroscopy offers the significant advantages of simple sample preparation and expeditious operation. 

Mass spectrometry is an analytical technique to measure molecular masses and to elucidate the structure of molecules by recording the products of their ionization. The mass spectrum is a unique characteristic of a compound. In general it contains information on the molecular mass of an analyte and the masses of its structural fragments. An ion with the heaviest mass in the spectrum is called a molecular ion and represents the molecular mass of the analyte. Because atomic and molecular masses are simple and well-known parameters, a mass spectrum is much easier to understand and interpret than nuclear magnetic resonance (NMR), infrared (IR), ultraviolet (UV), or other types of spectra obtained with various physicochemical methods. Mass spectra are represented in graphic or table format (Fig. 5.1). 

Although Eibner elucidated the structure between 1904 and 1906, it was only through IR and nuclear magnetic resonance spectroscopy (NMR) that the chro-maticity of these molecules could be attributed to keto-enol tautomerism and simultaneous hydrogen bond formation (structures 137a = 137b) [2]. 

A solution-state and solid-state nuclear magnetic resonance study of the complex and its separate components in both their neutral and ionized (TMP hydrochloride and SMZ sodium salt) forms was undertaken in order to elucidate the TMP-SMZ interactions. Inspection of the data for the complex in the solid state shows that the 13C chemical shifts are consistent with the ionic structure proposed by Nakai and coworkers105 (14). Stabilization of the complex is achieved by the resulting ionic interaction and by the formation of two intermolecular hydrogen bonds. 

The fourth chapter in this volume, contributed by Helmut Duddeck, is an exceptionally thorough survey of substituent effects on carbon-13 nuclear magnetic resonance (NMR) chemical shifts. Organic chemists and others who are routinely dependent on 13C NMR for structure elucidation and for information about stereochemistry will welcome the summary presented here. Although... 

Following hits, the lead compounds are purihed using chromatographic techniques and their chemical compositions are identihed via spectroscopic and chemical means. Structures may be elucidated using X-ray or nuclear magnetic resonance (NMR) methods. 

Hyphenated analytical techniques such as LC-MS, which combines liquid chromatography and mass spectrometry, are well-developed laboratory tools that are widely used in the pharmaceutical industry. Eor some compounds, mass spectrometry alone is insufficient for complete structural elucidation of unknown compounds nuclear magnetic resonance spectroscopy (NMR) can help elucidate the structure of these compounds (see Chapter 20). Traditionally, NMR experiments are performed on more or less pure samples, in which the signals of a single component dominate. Therefore, the structural analysis of individual components of complex mixtures is normally time-consuming and less cost-effective. The... 

On the other hand, nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful tools for the structure elucidation of organic compounds. However, to solve the molecnlar strnctnre of a novel substance by NMR spectroscopy alone is often time-consnming (when compared to MS). Besides, the identification of components in a complex mixture usually requires the separation and/or isolation of the components of interest prior to NMR analysis. Therefore mnltiple preparatory chromatographic... 

Elucidation of the structure of the cycloadducts (3) by nuclear magnetic resonance is simplified by the strong deshielding effect of the positively... 

Chaffee AL, Fookes GJR, Polycyclic aromatic hydrocarbons in Australian coals— III. Structural elucidation by proton nuclear magnetic resonance spectroscopy, Org Geochem 12 261—271, 1988. 

Xiao, H. B., Krucker, M., Putzhach, K., and Albert, K., Capillary liquid chromatography-microcoil IH nuclear magnetic resonance spectroscopy and liquid chromatography-ion trap mass spectrometry for on-hne structure elucidation of isoflavones in Radix astragali. Journal of Chromatography A 1067(1-2), 135-143, 2005. 

The hyphenation of capillary electromigration techniques to spectroscopic techniques which, besides the identification, allow the elucidation of the chemical structure of the separated analytes, such as mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) has been widely pursued in recent years. Such approaches, combining the separation efficiency of capillary electromigration techniques and the information-rich detection capability of either MS or NMR, are emerging as essential diagnostic tools for the analysis of both low molecular weight and macromolecular compounds. 

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