Application of the Nuclear Overhauser Effect

In the case of some complex compounds like tubingensin A and B (20 and 21) the more precise INEPT method has been utilised (779, 120). 

Compound Aromatic protons Protons of groups on the aromatic ring and other protons 

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Bell, R. A., Some Chemical Applications of the Nuclear Overhauser Effect, 7, 1. 

More quantitative information about host-guest proximity may be obtained by application of the nuclear overhauser effect (NOE). Very simply, the NOE involves the saturation of the spin of one nucleus by continuous irradiation, and monitoring the resulting intensity enhancements of the NMR resonances of adjacent atoms. The idea is that the irradiation of one nucleus causes it to become excited to a nonequilibrium distribution of spin states. Relaxation of this excited state situation occurs by dipole-dipole spin-lattice transfer of the excess energy, resulting in enhancement of the intensity of signals for nuclei physically close to the irradiated nucleus, irrespective of whether they are actually bonded. NOE intensity enhancements may be anywhere... 

Alkylation of the dienolate ion derived from 4-methyl-19-nortestosterone (313) with CD3I in benzene solution gave the 4,4-dimethyl compound (314), with 70% of the labelled methyl groups in the 4j5-orientation. With t-butyl alcohol as solvent the product showed predominant (90%) introduction of 4a-CD3 (iWs latter conclusion, which reverses that reached in an earlier study, depended upon application of the nuclear Overhauser effect for the assignment of n.m.r. signals of the C-4 methyl groups). Solvent-dependence of the stereochemistry of alkylation has not been suspected before. ... 

Kotovych G, Aarts G H M 1982 Application of the nuclear Overhauser effect difference experiment assignment of the configuration of carboprostacyclin. Org Magn Res 18 77-81... 

Nakano, T, Rivas, C., and Perez, C., Configuration and stereochemistry of photoproducts by application of the nuclear overhauser effect adducts of benzophenone with methyl-substituted furans and 2,5-dimethylthiophene, and of methyl-substituted maleic anhydrides with thiophene and its methyl derivatives, and benzojb] thiophene, /. Chem. Soc., Perkin Trans. 1, 2322, 1973. 

Phytochemical studies on Narcissus obesus have resulted in the isolation of a new alkaloid named obesine (420) (see Fig. 24), accompanied by several known Amaryllidaceae alkaloids (74). The stereochemistry and structural determination of the alkaloid 420 have been carried out by spectroscopic analyses and by application of 2D NMR techniques. Although the H-6)8 proton (5 4.38) is masked by the H-3 proton (5 4.30-4.40), the H-6a proton (54.02) was assigned at higher field on the basis of the nuclear Overhauser effect (NOE) with H-12 endo (5 3.10) observed in the 2D NMR experiment. On the other hand, the a disposition of H-3 was confirmed by the NOE between H-3 (5 4.30-4.40) and H-12 exo (5 3.01). In the C-NMR spectrum of 420 a characteristic signal due to the C-11 carbon was observed at 82.7 (singlet) ppm. Also, a comparison of the H and NMR spectra of obesine (420) with those of the related alkaloid 3-epi-marconine (303) (50) was performed. 

The Solomon equations are an excellent way of understanding and analysing experiments used to measure the nuclear Overhauser effect. Before embarking on this discussion it is important to realize that although the states represented by operators such as Iz and Sz cannot be observed directly, they can be made observable by the application of a radiofrequency pulse, ideally a 90° pulse... 

Older methods based on solubility changes upon complexation, or on partition coefficients between aqueous solutions and hydrophobic solvents, have been shown to lead to gross errors as compared to spectroscopic techniques (40) that are also less sensitive to the formation of emulsions, micelles, and so on. The traditional X-ray analysis of inclusion compounds is of limited significance for establishing complexation between lipophilic substrates and macrocyclic host, particularly in aqueous solution. The essential hydrophobic driving force for complexation, of course, is nonexistent in the crystal. The future development of NMR methods including shielding calculations and measurements of intermolecular nuclear Overhauser effects is expected to provide the most reliable information on intercavity inclusion complexes in solution as the basis for catalytic applications. 

While the Nuclear Overhauser effect is not of general application in most laboratories, the authoritative article on this subject will clarify many misconceptions of ideas associated with this technique. 

Homonuclear correlation via the nuclear Overhauser effect (NOESY). The NOESY experiment correlates peaks by means of the nuclear Overhauser enhancement and so identifies pairs of nuclei which are sufficiently close together in space to relax by their dipole-dipole interaction. This technique is not so applicable in determining stereochemical assignments as those described previously, but may be extremely useful in determining the chain conformation as demonstrated by Mirau et al. in a study of the alternating copolymer of styrene and methyl methacrylate [45] (see chapter 4). 

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