Conformational studies on pyranoid sugar derivatives by NMR spectroscopy. Correlations of observed proton—proton coupling constants with the generalized Karplus equation

Proton spin-spin coupling values measured for a wide range of tetrasubstituted tetrahydropyran ring-systems obtained from aldopentopyranose sugars have been correlated with values calculated from a generalized version of the Karplus equation which takes into account the electronegativities of the various atoms in the molecule and the configurations of these substituents. Minor discrepancies between observed and calculated values can be attributed to slight flattening of the tetrahydropyran ring as a result of steric interactions of the substituents. The magnitude of the geminal coupling J_5e,5a of these aldopentopyranose derivatives provides a rough measure of the conformational population; when H-4 is axial [Cl(D) or 1C(L ) conformation] J_5e,5a is ～10.9 Hz, and is ～13.4 Hz when H-4 is equatorial [1C(D ) or Cl(L ) conformation].     

Conformational preference of substituted naphthalenes. 2—proton–proton coupling constants of hydroxy derivatives of naphthalene

Long-range proton–proton coupling constants between the hydroxy proton and ring protons were employed to deduce the conformational preferences of 1- and 2-hydroxynaphthalene. 2,6-Dibromo-1,5-dihydroxy-naphthalene, 2-acetyl-1-hydroxynaphthalene, 1,6-dibromo-2-hydroxynaphthalene and 2-hydroxy-1-naphthaldehyde were used as model compounds. Molecular orbital calculations at the CNDO/2 and INDO level were used to calculate the energy and the long-range proton–proton coupling of different conformers of 1- and 2-hydroxynaphthalene.     

Interpretation of vicinal proton–proton coupling constants of heteroaromatic molecules in terms of topological electron density descriptors

The indirect vicinal proton–proton coupling constants for pyrrole, furan, thiophene and 15 related heteroaromatic compounds were calculated using the Khon–Sham approximation. An analysis of the four Ramsey contributions to the coupling constants was carried out showing that the Fermi contact term is always positive and dominant, although the remaining contributions have a nonnegligible net negative contribution. The trends observed for the proton–proton coupling constants were rationalized in terms of the properties of the electron density. It was found that electron delocalization between the corresponding hydrogen atoms plays a major role on the observed behavior with the charges of the carbon atoms bonded to them and the accompanying geometric variations being also of importance in the coupling mechanism. Copyright © 2010 John Wiley & Sons, Ltd.     

Stereochemical studies: XVII—the proton coupling constants and conformational equilibria of trans-1,2-disubstituted cyclohexenes

The vicinal ³J_aa and ³J_ee spin-spin coupling constants of a number of deuterated trans-1,2-disubstituted cyclohexenes and the ΔH and ΔS values of the conformational equilibria of these compounds have been determined by computer optimisation of the ³J(HH) = f(T) function. Compounds with —CF₃ and CCl₃ substituents were shown to have an enhanced proportion of the diaxial conformer.     

J‐modulated 1D directed COSY for precise measurement of proton–proton residual dipolar coupling constants of oligosaccharides

A simple selective 1D experiment for the accurate and precise determination of residual proton–proton dipolar coupling constants of oligosaccharides is proposed. The technique is based on the concept of J‐modulated spectroscopy and provides coupling constants by fitting the peak intensities from a series of spectra to known transfer functions with a precision of ±0.02 Hz for splittings >0.3 Hz. This level of precision is possible owing to limiting the number of sites for polarization transfer. Selective pulses and pulsed field gradients are used for selective excitation and coherence selection, yielding clean, artefact‐free spectra. The technique is illustrated using trisaccharide samples in Pf1 phage. Copyright © 2002 John Wiley & Sons, Ltd.     

1,2-oxazine chemistry. V—vicinal,allylic and homoallylic coupling constants in the 3,6-dihydro-1,2-oxazine ring

The ¹H NMR spectra of thirteen dihydro-1,2-oxazine derivatives are reported. Spin decoupling allows analysis of the spectra, features of which include homoallylic couplings of +2 to +2·5 Hz, allylic couplings of ?1·5 to ?1·7 Hz and vicinal couplings across sp² to sp³ carbon–carbon bonds of +2·9 to +3·7 Hz.     

Conformational study of 1,2-cycloundecadiene by dynamic NMR spectroscopy and computational methods

Solutions of 1,2-cycloundecadiene in propane were studied by low-temperature (13)C NMR spectroscopy. A total of 17 peaks were observed at -166.7 degrees C, corresponding to two conformations of similar populations, one of C(1) symmetry (11 peaks) and the other of C(2) symmetry. The line shapes show that the predominant pathway for exchange of the topomers (C(1) and C(1)') of the C(1) conformation does not include the C(2) conformation. From the (13)C spectra, free-energy barriers of 8.38 +/- 0.15, 9.45 +/- 0.15, and 9.35 +/- 0.15 kcal/mol were determined for the C(1) to C(1)', (C(1) + C(1)') to C(2), and C(2) to (C(1) + C(1)') conversions, respectively, at -72.2 degrees C. The NMR results for this compound are discussed in terms of the conformations predicted by molecular mechanics calculations obtained with Allinger's MM3 program. Ab initio calculations of free energies are also reported at the HF/ 6-311G level for 25 conformations.     

The relationship between proton–proton NMR coupling constants and substituent electronegativities. II—conformational analysis of the sugar ring in nucleosides and nucleotides in solution using a generalized Karplus equation

The relationship between vicinal NMR proton–proton coupling constants and the pseudorotational properties of the sugar ring in nucleosides and nucleotides is reinvestigated. Compared with our earlier study several important improvements are introduced: first, a new empirical generalization of the classical Karplus equation is utilized, which allows an accurate correction for the effects of electronegativity and orientation of substituents on ³J(HH); second, empirical correlations between the parameters governing the conformation of β-D -furanosides (taken from an analysis of 178 crystal structures) were used to define proton–proton torsion angles as a function of the pseudorotation parameters P and Φ_m; and, third an iterative least-squares computer program was devised to obtain the best fit of the conformational parameters to the experimental coupling constants. NMR data for the sugar ring in the following compounds were taken from the literature and analysed: 3′,5′-cyclic nucleotides, a base-stacked ribonucleotide, 2′-anhydroarabinonucleosides, α-D -2′,2-O-cyclouridine, 2′- and 3′-aminosubstituted ribonucleosides, 2′- and 3′-deoxyribonucleosides. The present results confirm that the conformational properties found in the solid state are, on the whole, preserved in solution.     

Psi-angle dependence of geminal proton–carbonyl-13C coupling constants in peptides. A theoretical investigation

Theoretical calculations of the geminal carbonyl-¹³C- proton coupling constant, ²J(C′H), in α-amino acids have been carried out using Dirac Vector model and Penney-Dirac bond order formulations. The results indicate that the couplings are dependent on the backbone torsion angle psi (ψ) of the amino acid residues in peptides. The meagre available experimental data seem to support the theoretical findings.     

Spectroscopic studies on olefins. VII–propene and 3-methylbutene-1; proton NMR coupling constants as a function of solvent and temperature in relation to molecular geometry

The proton spectra of the compounds propene (1) and 3-methylbutene-1 (2) have been measured in various solvents and, as neat liquids, at variable temperature. The effects of solvent and temperature on 1 are found to be small, but not negligible. The effect of temperature on the coupling constants of 2 are more pronounced, which is explained in terms of an anti-gauche equilibrium. To obtain a consistent ΔE° value from each temperature dependent coupling constant it is necessary to correct for the non-conformational temperature effects (obtained from 1) as well as to correct for changes in the geometry of the entire molecule, which are concurrent with a conformational transition. Such geometry changes have been calculated by a consistent force field technique, which, when coupled with INDO-MO calculated dependencies of coupling constants on valence (and torsional) angles, provided the changes in coupling constants. The observed temperature dependence of the coupling constants of the H₂C?CH— moiety of 2 could be satisfactorily explained in this fashion. The difference in energy between the anti and gauche forms of 2 were determined as ΔE° = 127 ± 14 cal mol^?1.     

BASHD‐J‐resolved‐HMBC,an efficient method for measuring proton–proton and heteronuclear long‐range coupling constants

Natural products often possess various spin systems consisting of a methine group directly bonded to a methyl group (e.g. –CH_a–CH_b(CH₃)–CH_c–). The methine proton H_b splits into a broadened multiplet by coupling with several vicinal protons, rendering analysis difficult of ⁿJ_C–H with respect to H_b in the J‐resolved HMBC‐1. In purpose of the reliable and easy measurements of ⁿJ_C–H and ⁿJ_H–H in the aforesaid spin system, we have developed a new technique, named BASHD‐J‐resolved‐HMBC. This method incorporates band selective homo decoupled pulse and J‐scaling pulse into HMBC. In this method, high resolution cross peaks can be observed along the F₁ axis by J‐scaling pulse, and band selective homo decoupled pulse simplified multiplet signals. Determinations of ⁿJ_C–H and ⁿJ_H–H of multiplet signals can easily be performed using the proposed pulse sequence. Copyright © 2013 John Wiley & Sons, Ltd.     

Non‐empirical calculations of NMR indirect carbon–carbon coupling constants: 2. Strained polycarbocycles

High‐level non‐empirical calculations of carbon–carbon spin–spin coupling constants in a series of strained polycarbocycles have been carried out, in excellent agreement with available experimental data. The utmost importance of electronic correlation effects in this case has been demonstrated and it has been shown that the Second‐Order Polarization Propagator Approach (SOPPA) is an adequate method to account for those effects. It has been demonstrated that the most reliable basis sets to calculate J(C,C) at the SOPPA level are the correlation‐consistent basis sets of Dunning and co‐workers augmented with inner core s‐functions or decontracted in their s‐parts. The nature of the unusual bridgehead–bridgehead bonds in bicyclobutane and propellane in terms of s‐characters of bonding hybrids and also the hybridization effects in spiropentane are discussed based on the arguments derived from the current calculations of J(C,C) in the title compounds. The values of the unknown J(C,C) in propellane and spiropentane are predicted with high reliability. Copyright © 2003 John Wiley & Sons, Ltd.     

Selective J‐resolved‐HMQC‐1 and ‐2, new methods for measuring proton–proton coupling constants in strongly coupled spin systems

Efficient pulse sequences for measuring ¹H–¹H coupling constants (J_HH) in strongly coupled spin systems, named selective J‐resolved‐HMQC‐1 and ‐2, have been developed. In the strongly coupled spin systems such as ‐CH₂‐CH_A(OH)‐CH_B(OH)‐CH₂‐, measurements of ³J_HAHB are generally difficult owing to the complicated splitting caused by the adjacent CH₂ protons. For easier and accurate measurements of ³J_HAHB in such a spin system, a selective excitation pulse is incorporated into the J‐resolved HMQC pulse sequence. In the proposed methods, only two strongly coupled protons, H_A and H_B which are excited by a selective pulse, are observed as J‐resolved HMQC signals. The cross peaks of H_A and H_B appear as doublets owing to ³J_HAHB along the F₁ dimension in the selective J‐resolved HMQC‐1 and ‐2 experiments. The efficiency of the proposed pulse sequences has been demonstrated in application to the stereochemical studies of the complicated natural product, monazomycin. Copyright © 2011 John Wiley & Sons, Ltd.     

Conformational studies of some 2-phenylpropyl derivatives by NMR spectroscopy and use of lanthanide shift reagents

The conformational distribution of CH₃CH(Ph)CH₂X (X = OH, OCH₃, NH₂ Cl) has been studied by NMR and IR spectroscopy. The results are interpreted in favour of the conformers with methoxy- or chloro-groups anti to the phenyl group, but the amino group anti to the methyl group. For the alcohol both forms are about equally populated. It is suggested that intra-molecular hydrogen bonding might be affecting the conformational equilibria when X = OH, NH₂.     

Molecular structure and the indirect spin–spin coupling constants in azulene—a proton NMR study in the nematic phase

The proton NMR spectrum of azulene has been investigated in the nematic phase of a liquid crystal. Spectral analysis provided the direct dipole-dipole coupling constants which were used to derive the structural information. It was found that the relative proton-proton distances in the 7- and 5-membered rings deviate significantly from those for regular heptagons and pentagons. Indirect spin-spin couplings were also obtained. Many of the inter-ring and long-range couplings have magnitudes between 0.2–0.8 Hz.     

Non‐empirical calculations of NMR indirect carbon–carbon coupling constants: 3. Polyhedranes

High‐level ab initio calculations of carbon–carbon coupling constants were carried out in tetrahedrane, prismane and cubane using the SOPPA (Second‐Order Polarization Propagator Approach) computational scheme, in good agreement with available experimental data. It was found that SOPPA performs perfectly well in combination with Dunning's correlation‐consistent basis sets augmented with inner core functions; however, no improvement was observed on adding tight s‐functions. The utmost importance of electronic correlation effects decreasing the total values of computed J(C,C) in the title compounds by a factor of ～2.0–2.5 was found. Unknown values of J(C,C) in the title polyhedranes were predicted with high reliability and the latter were treated in terms of s‐characters of carbon–carbon bonds based on the additive scheme of coupling pathways. All three compounds under study showed decreased s‐characters of their carbon–carbon bonds, which is the result of their remarkable steric strain. Copyright © 2003 John Wiley & Sons, Ltd.     

Modern proton‐detected 1D 1H–15N NMR experiments. Application to the measurement of 1H,15N coupling constants at natural abundance

Non‐selective and selective versions of several proton‐detected 1D NMR experiments to be applied to ¹⁵N are proposed. Clean, artifact‐free 1D spectra are easily obtained by the effective coherence selection by pulsed‐field gradients and the attainable sensitivity is maximized using modern pulse schemes. Despite the low sensitivity inherent to ¹⁵N NMR spectroscopy, the successful application of these experiments is demonstrated for resonance assignments and accurate measurement of both one‐bond and long‐range proton–nitrogen coupling constants on a model tripeptide at natural abundance. Copyright © 2001 John Wiley & Sons, Ltd.     

Conformational studies of novel estrogen receptor ligands by 1D and 2D NMR spectroscopy and computational methods

The solution conformations of the novel estrogen receptor ligands (17α,20E)‐(p‐trifluoromethylphenyl)vinylestradiol ( 1 ) and (17α,20E)‐(o‐trifluoromethylphenyl)vinylestradiol ( 2 ) were investigated in 2D and 1D NOESY studies and by comparison of ¹³C NMR chemical shifts with theoretical shieldings. The ¹H and ¹³C assignments of 1 and 2 were determined by DEPT, COSY and HMQC experiments. The conformations of the 17α‐phenylvinyl substituents of 1 and 2 are of interest because of their differing receptor binding affinities and effects in in vivo uterotrophic growth assays. A statistical method of evaluating contributing conformers of 1 and 2 from predicted ¹³C shifts of possible structures correlated fairly well with conformational conclusions derived from the NOE data. The 17α substituents of 1 and 2 apparently exist in similar conformational equilibria, suggesting that while 1 and 2 would occupy a similar receptor volume, interactions with the protein may shift the equilibrium and thereby influence the expression of the ligand. Copyright © 2003 John Wiley & Sons, Ltd.     

Conformational studies of monoterpenes. II–conformational studies of bicyclo[3.1.1]heptane derivatives by 13C NMR

The carbon-13 spectra of seventeen bicyclo[3.1.1]-heptane derivatives have been recorded and assigned. Study of the C-6 and C-7 chemical shifts permits the conformations to be assigned to the bridged chair, Y-shaped, or bridged boat conformations. The spectrum of verbenone is anomalous and is compared to that of umbellulone recorded earlier.