Use in Structural Elucidation

NMR was first used in structural elucidation of carotenoids for peridinin (30) (108, 160, 161). Support for the presence of the allo-xanthin (31) end group in isomytiloxanthin (20) was obtained by direct comparison of NMR spectra (114, 175). From the characteristic shifts of the 14-methyl and C-8 signals violeoxanthin was shown to be the 9-ds isomer of violaxanthin (32) (136). 

The structure of the C-5 monomethyl ether of azafrin (6) methyl ester was determined by partial analysis of the NMR spectrum (170), and a new isomer of phytoene (21) has been assigned the Z,E,Z or Z,E,E configuration from NMR evidence (18). Further application of NMR spectroscopy for the structural elucidation of carotenoids will be facilitated by the assigned spectra of authentic carotenoids gradually available. 

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The coupling constants of ortho ( Jhh = 7 Hz), meta Jhh =1-5 Hz) and para protons CJhh I Hz) in benzene and naphthalene ring systems are especially useful in structure elucidation (Table 2.5). With naphthalene and other condensed (hetero-) aromatics, a knowledge of zig zag coupling = 0.8 Hz) is helpful in deducing substitution patterns. 

The chemical shift of a nucleus depends in part on its spatial position in relation to a bond or a bonding system. The knowledge of such anisotropic effects is useful in structure elucidation. An example of the anisotropic effect would be the fact that axial nuclei in cyclohexane almost always show smaller H shifts than equatorial nuclei on the same C atom (illustrated in the solutions to problems 37, 47, 48, 50 and 51). The y-effect also contributes to the corresponding behaviour of C nuclei (see Section 2.3.4). 

FTIR Solute confirmation Less informative than MS Limited use in structure elucidation [31]... 

The underlying physical principles of NMR have been established and are well understood.8 Applications of both solid- and solution-state NMR spectroscopy can be found in many different disciplines. It is routinely used in structural elucidation of organic and inorganic compounds, polymers, and biomolecules (e.g., proteins, nucleic acids, and carbohydrates). Additionally, NMR can be used to study molecular interactions (e.g., protein-protein and protein-ligand), molecular dynamics, and chemical reactions. It has also been used extensively in medical research and imaging (magnetic resonance imaging). 

Studies of other sources of ceruloplasmin may eventually prove useful in structure elucidation, but have already clarified some of the copper chemistry. Ceruloplasmin from goose serum has been isolated, purified, and characterized. This ceruloplasmin has less carbohydrate attached, but two forms may be isolated under some conditions. It is clear that these are not products of proteolytic degradation, but perhaps they might have a different carbohydrate attached. The two type I sites have higher extinction coefficients than type I sites in other ceruloplasmins, reflecting a modestly different environment (Hilewicz-Grabska et al, 1988). 

The work discussed in this article serves to illustrate the applicability of gel chromatography to a wide variety of carbohydrates. The technique can be used not only as a means of fractionation but also, provided that the relationship between molecular weight and such other molecular parameters as size and shape remains constant, as a method of estimating the molecular weights of polysaccharides. Often, information derived from gel chromatography has proved useful in structural elucidation. 

Direct 3H observation should be much more direct and straightforward for rapid use in structure elucidation, preferably in a ID spectrum, and most subsequent attempts focussed on maintaining that speed and utility. Spin-echoes were applied first,34,45 utilizing the differences in transverse relaxation rates between the cross-linked polymer and relatively more mobile resin-bound molecule of interest. Wehler and Westman also had some success applying pre-saturation to the resin signals.34 While some attenuation is afforded, it is at the expense of some spectral intensity from the resin-bound molecule... 

The furanoid ring in benzo[6 ]furan is susceptible to attack by oxidants. Permanganate and chromic acid give derivatives of 2-hydroxybenzoic acid with compounds unsubstituted at the 3-position, but compounds with a 3-methyl or a 3-aryl substituent give derivatives of 2-hydroxyacetophenone or 2-hydroxybenzophenone. Ozonolysis of benzo[6]furan affords 2-hydroxybenzoic acid, 2-hydroxybenzaldehyde and some catechol produced via its diformate. Before the advent of NMR spectroscopy these methods were used in structural elucidation of benzofuranoid natural products, as in the case of O-methyleuparin (Scheme 26). 

The changes in the spectral parameters of hydroxycoumarins brought about by the addition of acids or bases are of value in structural elucidation (60JOC2183, 67JCS(C)2545). For example, both 5- and 7-hydroxycoumarins show red shifts and increases in intensity upon the addition of base, whereas for the 6- and 8-substituted compounds the bathochromic shift is accompanied by a reduction in intensity (69JCS(C)526). Several other additives have proved useful in structure elucidation, notably sodium acetate (66IJC120) and aluminum chloride (69MI22201). ... 

Covalently-bound addition complexes have been shown to result from the reactions of a wide variety of aromatic compounds, activated by one or more nitro-groups, with bases or other nucleophilic species. In some cases di-adducts or tri-adducts are also formed by the addition of more than one molecule of base. There is considerable current interest in these adducts and this article will be concerned with their structures and stoichiometries and with the factors governing their stabilities. The second section deals with the spectroscopic and chemical studies which have been used in structural elucidations. Some general principles... 

All these calculations will be achievable with PCs of the early- to mid-1990s. An example of an advanced NMR data reduction procedure is shown in Figure 10.1. The contrast enhancement achievable with maximum likelihood reconstruction can be put to good use in structure elucidation of biomolecules such as small nucleic acids and proteins. 

At sufficient concentration and in the absence of disturbing background resonances, NMR is the superior method both for the identification of known chemicals and for the structural elucidation of unknown chemicals. Its usefulness in identification is attributable to the fingerprint nature of spectra, while the usefulness in structural elucidation rests on the structural specificity of the spectra. The wide variety of routine 1-D and 2-D experiments available is of assistance in both identification of chemicals and structure elucidation. 

Vch for C-3 is frequently larger than the other 1JCh values, a feature which has proved useful in structure elucidation amongst the coumarins. Typically, 2/ch values are no larger than 4 Hz, three-bond coupling constants are in the 4-10 Hz range and 4/ch values are less than 2 Hz. 

There are numerous attempts to channel the different empirical observations and geometry dependences chemical shifts into predictive schemes, and some of them have been successfully used in structure elucidation. One of these models is CHARGE(X) where X reached 5 in recent publications. The central point is that for protons and certain other resonances a correlation of atomic charges with chemical shifts was observed. Within the framework of the bond polarization theory we arrive in the case of a proton at a linear dependence with just one parameter for its chemical shift and for the atomic charge. Therefore, one dependence can be easily calculated from the other. 

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