NOE studies

However, 2D NOE studies are invaluable in structure determination, in particular of peptides and proteins here the NOEs give invaluable information for conformational analysis and the determination of the tertiary structures of proteins. 

Figure 27 Molecular structure of thiophene used in the NMR NOE study [139].

When one resonance in an NMR spectrum is perturbed by saturation or inversion, the net intensities of other resonances in the spectrum may change. This phenomenon is called the nuclear Overhauser effect (NOE). The change in resonance intensities is caused by spins close in space to those directly affected by the perturbation. In an ideal NOE experiment, the target resonance is completely saturated by selected irradiation, while all other signals are completely unaffected. An NOE study of a rigid molecule or molecular residue often gives both structural and conformational information, whereas for highly flexible molecules or residues NOE studies are less useful. 

Naphthopyran mero-forms have been studied using H-NMR and NOE studies [78,79]. It has been concluded that there are two isomeric forms that are possible for the mero-form when the terminal methine carbon atom (Cl in Scheme 1 and C42 in Fig. 10) is symmetrically substituted, as shown in Scheme 1. A fourth species has been identified in photo-stationary states of naphthopyran and its mero-forms however, this has not yet been clearly identified. The two main mero-isomers are not in rapid exchange, as two peaks can be clearly identified in the H-NMR spectrum. 

Early NOE studies on cationic Pd(ii) allyl complexes used reporter ligands [97, 98], i. e. simple bidentate nitrogen ligands, such as bipy or phenanthroline, whose... 

Whereas the simple bidentate nitrogen ligands proved to be rather limited, the frequent occurrence of a set of four P-phenyl or alkyl substituents, e. g., in coordinated Binap, MeO-Biphep, Josiphos or Duphos (shown, from left to right in Scheme 1.4), offered many more reporters . In this way, one can develop a more detailed NOE picture of how the complexed substrate interacts with the chiral pocket offered by these auxiliaries. From these NOE studies [97, 98] it can be shown that the atropisomeric bidentate ligands Binap and MeO-Biphep tend to have fairly classical axial and equatorial P-phenyl substituents. 

An NOE study of the intermediate [Pd(ti -PhCHCHCHPh)(Binap)], 82, thought to be involved in the Pd-catalyzed allylic alkylation of a 1,3-diphenylpropene, revealed that two phenyl rings, one from the auxiliary, D, and one from the substrate, F, are forced to take up parallel positions, i.e, they are 7i-stacked, as shown in 83 [103]. Since the ti-stacking is repulsive, and thus selectively weakens one of the two Pd-C(allyl) bonds, the reaction becomes stereoselective. The D and F rings do not show inter-ligand NOEs. 

These NOE studies teach us that many successful P (or N...etc) auxiliaries possess a relatively rigid and intrusive chiral pocket [105, 107]. The shape of this pocket is a function of the individual chelate ligand, i. e., there is no one successful shape. 

The murrastifolines exhibited characteristic carbazole UV spectra. Their H-NMR spectra showed signals for aromatic methoxy ((5 3.57-4.11) and methyl groups ( 2.52-2.56). In the aromatic region, signals of a four-spin system and two singlets for H-4 (6 7.56-7.63) and H-2 (S 6.85-7.00) were observed. The H-NMR spectra, NOE studies, and mass fragments at m/z 210 or 211 confirmed murrayafoline A (7) as the common structural unit for all murrastifolines (Schemes 2.42-2.44). 

Although one diastereomer 10 was largely favored, the product was obtained as a mixture of diastereomers, and the previously unreported minor diastereomer 11 was also characterized. The stereochemistry of the products was established by nuclear Overhauser effect (NOE) studies. A plausible mechanism assumes the intermediacy of an acetal, and its reaction with 2-methoxypropene generated from 2,2-dimethoxypropane [20]. In order to test this mechanism, the dimethyl acetal of salicylaldehyde was synthesized and reacted independently with both 2,2-dimethoxypropane and 2-methoxypropene. Indeed, both reactions gave the same products as those from the reaction of salicylaldehyde with 2,2-dimethoxypropane (Scheme 4). The condensation of salicylaldehyde and 2,2-dimethoxypropane was also carried out in CD3CN and reaction progress was followed by H NMR spectroscopy. This experiment also confirmed the formation of the acetal from salicylaldehyde (8 5.52, singlet, C//(OMe)2). 

Taking these factors into consideration 21 was proposed as the most likely structure. Recent NOE studies on the N-methyl analog of schumannificine (26) have proposed that schumannificine should in fact have structure 25 (12) although this was rejected by the original authors. When Houghton and Yang isolated Schumannificine they showed that it consisted of a 5 1 mixture of the 8-OH a and 8-OH 3 isomers by consideration of the duplicate peaks in the H-NMR spectrum (77). The diacetates of the two isomers could be separated. 

Hatano and Hemingway used NOE studies to assess the association of catechin and procyanidin B-3 with oligopeptides (see also relevant results in Refs. 253-256). The observed intermolecular NOEs indicating the preferred sites in the association of catechin and procyanidin B-3 with the tetrapeptide Gly-Pro-Gly-Gly are shown in 232 and 233, respectively. The molecular shapes of both the polyphenol and polypeptide are important features as far as selectivity is concerned. 

The conformations of a number of silyl-tethered nucleosides typified by 3, 5 -0-(di- /t-butylsilanediyl)-adenosine 3, have been studied by NMR spectroscopy <1993MRC1039>. The conformational bias in such systems was used to determine the stereochemistry of compound 4 by NOE studies <1998NN1033>. 

The [2,3] Wittig rearrangement151 of the optically active tertiary allyl ether 10 derived from ( + )-camphor yields the two olefin products 11 and 12 in a 70 30 (EjZ) ratio. The configuration around the double bond was established by NOE studies. The configuration at the newly formed carbinol center could also have been determined by spectroscopic means, but was assigned by a correlation sequence (see p 475)152. 

NOE studies have shown the pairwise nature of the P-CH2 protons of the cysteines of the iron(II) domain [34] the P-CH2 proton signals of the iron(III)... 

The preferred conformation of the 1,3-oxazepinone derivative 13 was shown to be the twist-boat conformer 14 on the basis of NOE studies and the coupling constants for couplings involving H6. A nuclear Overhauser effect (NOE) was only seen between H6 and H5a and not between H6 and H5b other NOEs are indicated on 14 <1999H(51)365>. 

The structure of tiliamosine, exclusive of stereochemistry, was deduced by NMR spin decoupling and NOE studies of 42 and the N-acetate of the related alkaloid nortiliacorinine A (44, Section II,B,5). The 100-MHz NMR spectrum of 42 very closely resembles that of 41, but 42 has an additional methoxy (8 3.88),... 

The structure 377 was originally assigned to the alkaloid (+)-hamayne based on spectroscopic considerations together with the fact that it could be converted to apohaemanthamine (407) on treatment with 6 N hydrochloric acid (20). Independent support for this structure was obtained from the intemuclear double resonance (INDOR) and NOE studies of the related alkaloid 3-O-acetylhamayne... 

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