Coupling constants and conformation

Altona C (1996) Vicinal Coupling Constants and Conformation of Biomolecules. In Grant DM, Harris RK (eds) Encyclopedia of Nuclear Magnetic Resonance. Wiley, New York, p 4909... 

C. Altona, Vicinal Coupling Constants and Conformation of Biomolecules. John Wiley London, 1996. 

Figure 12.68 The conformational dependence of vicinal coupling constants and conformational analysis of cyclohexanes and heterocyclohexanes.

In a further molecular mechanics study (MM3), the energy surfaces of a,a-, a,p-, and P,P-trehalose were compared with those of the corresponding 2-(6-methyltetrahydropyran-2-yloxy)-6-methyltetrahydropyrans and 5a-carba trehaloses it was concluded that the exo-anomeric effect plays an important role and that linkage-type (a or p) is more important than the presence or absence of exocyclic substituents in detomining disaccharide conformations. The preferred solution conformations of eight (l- )-C-linked disaccharides, such as compounds 13, have been determined on the basis of vicinal H- H coupling constants, and conformational similarities between... 

Rusakov, Y. Yu., Krivdin, L. B., Sauer, S. P. A., Levanova, E. R, and Levkovskaya, G. G. (2010). Structural trends of Se- H spin-spin coupling constants and conformational behavior of 2-substituted selenophenes. Magn. Reson. Chem., 48, 633-637. 

Application of NMR spectroscopy to heterocyclic chemistry has developed very rapidly during the past 15 years, and the technique is now used almost as routinely as H NMR spectroscopy. There are four main areas of application of interest to the heterocyclic chemist (i) elucidation of structure, where the method can be particularly valuable for complex natural products such as alkaloids and carbohydrate antibiotics (ii) stereochemical studies, especially conformational analysis of saturated heterocyclic systems (iii) the correlation of various theoretical aspects of structure and electronic distribution with chemical shifts, coupling constants and other NMR derived parameters and (iv) the unravelling of biosynthetic pathways to natural products, where, in contrast to related studies with " C-labelled precursors, stepwise degradation of the secondary metabolite is usually unnecessary. 

The NMR spectra of heterocyclic compounds with seven or more ring members are as diverse as the shape, size and degree of unsaturation of the compounds. NMR is perhaps the most important physical method to ascertain the structure, especially the conformational statics and dynamics, of large heterocycles. Proton-proton coupling constants provide a wealth of data on the shape of the molecules, while chemical shift data, heteroatom-proton coupling constants and heteronuclear spectra give information of the electronic structure. Details are found in Chapters 5.16-5.22. Some data on seven-membered rings are included in Table 10. 

It is difficult to decide whether the discrepancy between the calculated and experimental data is due to a different conformational preference of the thietane dioxides in the liquid and the solid phase, or to the crude approximations included in the Karplus-Barfield equation. However, the relationship between vicinal coupling constants and dihedral angles appears qualitatively valid in thietane oxides and dioxides, particularly if trends instead of exact values are discussed . At any rate thietane dioxides, 1,3-dithietane dioxides and tetroxides maintain either planarity or a slightly distorted average vibrating conformation with a low barrier to ring planarity . 

Haasnoot, C. A. G., De Leeuw, F. A. A. M., De Leeuw, H. P. M., Altona, C. Relationship between proton-proton NMR coupling constants and substituent electronegativities. III. Conformational analysis of proline rings in solution using a generalized Karplus equation. Biopolymers 1981, 20,1211-1245. 

Molecular mechanics (MM) calculations have been employed for determining dihedral angles and to establish a comparison with values calculated from coupling constants, during conformational studies of tricyclic and tetracyclic quinolizidine alkaloids. The MM results had to be treated with care, as they sometimes predicted ring conformations different to those supported by experimental data <1999JST215>. 

One example of the use of 2D-NMR experiments in conformational analysis is the study of molecular interactions between cinchonidine and acetic acid [26]. These alkaloids are used as chiral auxiliaries in enantioselective hydrogenations, and the enantiomeric excess is dependent on solvent polarity, acetic acid being a good solvent This suggests that protonation and a preferred conformation play a role in achieving high enantioselectivities. With a combination of COSY-experiments, 3J coupling constants and NOESY experiments, it was shown that one conformer is preferred in acidic solutions. 

There is no doubt that the most powerful tool for studying molecular structures in solution at the present time is NMR. Given the high sensitivity of chemical shifts and coupling constants to conformation and steric environment, an obvious expedient is to use MM-... 

These conformer populations were confirmed by a number of n.O.e. measurements (the H2—H5 distance can act as a marker in identifying the ring form). The case of a hexasaccharide (compound 23 in Ref. 9) where the three IdoA residues yield different n.O.e. enhancements, is striking. Moreover, models computed with molecular mechanics have been put forward for the peculiar pentasaccharide of heparin. The models are in acceptable agreement with the observed vicinal coupling constants and n.O.e. values (10) (a full paper by Ragazzi, M. et al. Carbohvdr. Res.. is in press). 

A careful analysis of the H and - C NMR spectral parameters (H,H coupling constants and shielding effects) established that the predominant conformation of the hetero ring for diexo-d ca- and d/ejco-l,2,3,4,4a,5,8,8a-octahydro-5,8-methano-3,l-benzoxazines is the endo-ho i 339A, whereas that for the corresponding diendo derivatives is the exo-boat 339B (85T5159). 

The intimate relationship between NMR parameters such as chemical shifts and spin-spin coupling constants and molecular geometry is particularly evident for derivatives with rigid frameworks. Therefore, structural and conformational effects are treated first as a separate topic and then in conjunction with specific compounds. As data on hydroxylamines, oximes and hydroxamic acids are not as extensive as those for other types of systems containing nitrogen or oxygen, comparisons with their respective parameters or effects have also been included wherever they are considered relevant. 

Discussion of NMR data have been organized according to the nucleus and type of parameter. They are used to exemplify general aspects of NMR data and are followed by more specific examples. This material is arranged by parameter (chemical shifts, coupling constants) and then by nucleus, in their order in the periodic table. Wherever general aspects of discussions of substituent or conformational effects are at hand, they are treated... 

Nuclear magnetic resonance (NMR) S Chemical shift, coupling constants, and spectroscopy nuclear Overhauser effect allows calculation of contact points, distances, and conformation... 

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