Long-range 13C 1H Coupling Constants Research Articles

ChemInform Abstract: 1H and 13C NMR Study of the Pyrazolo(1,5-a)pyrimidine System.

The 13C and 1H NMR spectra of some pyrazolo[1,5-a]pyrimidine derivatives are discussed. All 13C resonances were unambiguously assigned by means of both 2D experiments and gated decoupled spectra from which one-bond and long-range 13C–1H coupling constants were determined. The literature assignments for H-5 and H-7 in the parent system have been revised and a simple method for distinguishing between 5-methyl and 7-methyl compounds is suggested, based on the carbon chemical shift of the methyl group or on its fine structure in the 1H NMR spectrum. Regioselective syntheses for all the reported methyl derivatives are also described.

Development of a Method for the Measurement of Long‐Range 13C—1H Coupling Constants from HMBC Spectra

AbstractFor Abstract see ChemInform Abstract in Full Text.

Long-range 13C–1H coupling constants (3JC–H) of monensin sodium

Long-range 13C–1H coupling constants (3JC–H) of monensin sodium in CDCl3 and in CD3OD were measured by gs-J-HMBC experiments. The 3JC–H of monensin sodium was almost the same both in CDCl3 and in CD3OD. The obtained 3JC–H suggested a small difference in the conformation in solvents from that in crystals.

A flexible model for the cell wall polysaccharide of Streptococcus mitis J22 determined by three-dimensional 13C edited nuclear overhauser effect spectroscopy and 13C-1H long-range coupling constants combined with molecular modeling

We report on the conformation of a tetrasaccharide fragment in the repeating subunit of the cell wall polysaccharide of Streptococcus mitis J22, a receptor for the lectin of Actinomyces viscosus T14V in a bacterial coaggregation that is important in the ecological interactions of oral bacteria. Although there is considerable overlap of the 1H-nmr signals, some cross peaks can be extracted from conventional two-dimensional nuclear Overhauser effect spectroscopy (NOESY) data on the polysaccharide. These data cannot be fit to a single conformation of the tetrasaccharide fragment. Therefore we have prepared a polysaccharide sample fully enriched in 13C from which we have determined accurate NOESY cross-peak volumes in a three-dimensional heteronuclear-resolved spectrum that allows accurate determination of many more NOESY cross peaks than does conventional two-dimensional spectroscopy. We have also used the 13C enriched polysaccharide to measure accurate values of long-range 13C-1H coupling constants that can be correlated with glycosidic dihedral angles. Molecular modeling calculations on the polysaccharide fragment, including molecular dynamics simulations, identify multiple low-energy conformations. This result is to be contrasted with previous calculations on blood group oligosaccharides in our laboratory using similar methods that showed relatively rigid conformations with little flexibility of the glycosidic linkages. The present NOESY and 3JCH data can be reconciled with a model for the antigenic tetrasaccharide in which three distinct conformations are in fast exchange. We propose that some carbohydrate epitopes such as those of the blood group oligosaccharides are relatively rigid while others such as the tetrasaccharide fragment in these studies exhibit much greater flexibility. © 1996 John Wiley & Sons, Inc.

A flexible model for the cell wall polysaccharide of Streptococcus mitis J22 determined by three-dimensional 13C edited nuclear overhauser effect spectroscopy and 13C-1H long-range coupling constants combined with molecular modeling.

We report on the conformation of a tetrasaccharide fragment in the repeating subunit of the cell wall polysaccharide of Streptococcus mitis J22, a receptor for the lectin of Actinomyces viscosus T14V in a bacterial coaggregation that is important in the ecological interactions of oral bacteria. Although there is considerable overlap of the 1H-nmr signals, some cross peaks can be extracted from conventional two-dimensional nuclear Overhauser effect spectroscopy (NOESY) data on the polysaccharide. These data cannot be fit to a single conformation of the tetrasaccharide fragment. Therefore we have prepared a polysaccharide sample fully enriched in 13C from which we have determined accurate NOESY cross-peak volumes in a three-dimensional heteronuclear-resolved spectrum that allows accurate determination of many more NOESY cross peaks than does conventional two-dimensional spectroscopy. We have also used the 13C enriched polysaccharide to measure accurate values of long-range 13C-1H coupling constants that can be correlated with glycosidic dihedral angles. Molecular modeling calculations on the polysaccharide fragment, including molecular dynamics simulations, identify multiple low-energy conformations. This result is to be contrasted with previous calculations on blood group oligosaccharides in our laboratory using similar methods that showed relatively rigid conformations with little flexibility of the glycosidic linkages. The present NOESY and 3JCH data can be reconciled with a model for the antigenic tetrasaccharide in which three distinct conformations are in fast exchange. We propose that some carbohydrate epitopes such as those of the blood group oligosaccharides are relatively rigid while others such as the tetrasaccharide fragment in these studies exhibit much greater flexibility.

Carbon-13 NMR Studies on Azolopyridines. 4—The Tiazolopyridine Systems

The 13C NMR spectra of thiazolopyridine systems are discussed. One-bond and long-range 13C–1H coupling constants were determined from line splittings and a simple method for distinguishing between 2-methylthiazolo- and 3-methylisothiazolopyridines is suggested. © 1997 by John Wiley & Sons Ltd.

NMR Studies of Substituted 2,3-Diaminopropenoates

The orientation of substituted amino groups around the double bond in 2,3-diaminopropenoates, versatile agents in the syntheses of heterocyclic systems, was determined in solution by NMR techniques. Nuclear Overhauser enhancement and long-range 13C–1H coupling constants were measured by NOESY or ROESY and HMBC experiments, respectively. © 1997 John Wiley & Sons, Ltd.

Hadamard Long-Range Proton-Carbon Coupling Constant Measurements with Pulsed Field Gradients

Sources of artifacts in Hadamard spectra were investigated and identified as insufficient suppression of signals from solvent, protons attached to 12C atoms and error signals caused by non-ideal excitation and the subsequent Hadamard transformation. Pulsed field gradients (PFG) effectively eliminate the former error signals while re-optimized Hadamard-shaped pulses produce practically ideal excitation and Hadamard transformation affords artifact-free spectra. Long-range 13C–1H coupling constants of 1,6-anhydro-β-D-galactopyranoside and 3-acetylpyridine were determined by using a PFG pulse sequence and re-optimized Hadamard-8 shaped pulses.

NMR study of 6-azabicyclo[3.2.1 ]octene derivatives, by-products of catharanthine synthesis

The structures and stereochemistries of several 6-azabicyclo[3.2.1]octene derivatives, obtained by rearrangement reactions of the catharanthine synthesis, were determined by various NMR methods. Long-range 13C–1H coupling constants were measured by selective two-dimensional INEPT experiments. The dependence of 3J(C,H) and 2J(C,H) coupling constants on the dihedral angles and on the position of an electronegative substituent along the coupling path was studied.

1H and 13C NMR study of the pyrazolo[1,5-a]pyrimidine system

The 13C and 1H NMR spectra of some pyrazolo[1,5-a]pyrimidine derivatives are discussed. All 13C resonances were unambiguously assigned by means of both 2D experiments and gated decoupled spectra from which one-bond and long-range 13C–1H coupling constants were determined. The literature assignments for H-5 and H-7 in the parent system have been revised and a simple method for distinguishing between 5-methyl and 7-methyl compounds is suggested, based on the carbon chemical shift of the methyl group or on its fine structure in the 1H NMR spectrum. Regioselective syntheses for all the reported methyl derivatives are also described.

A conformational exploration of the protonated and unprotonated macrolide antibiotic roxithromycin: comparative study by molecular dynamics and NMR spectroscopy in solution

Molecular dynamics simulations (MD) have been performed on protonated and unprotonated roxithromycin, a novel macrolide antibiotic, using the crystallographic coordinates as the starting conformation in order to understand conformational changes. In all cases the 100 ps time scale seemed adequate for sampling an ensemble of solution conformers. Roxithromycin did not unfold appreciably during a 100 ps simulation while, for the protonated form, the desosamine unit underwent an interesting conformational reorganization (‘a⇔c’) during its evolution from the crystal structure form. MD indicate insignificant folding relative to the C(3)–C(5) region and it is believed that the necessary activation energy for this observed transitional event (‘A⇔B’) is probably not attained in solution, in contrast with erythromycin A. Long-range 13C–1H coupling constants are reported and correlated to the glycosidic torsional angles. The use of MD simulation has facilitated the confirmation of solution conformation as predicted by NMR spectroscopy. Moreover, it gives structural information on the different conformers present in solution. The data are not compatible with the conformation observed in the crystal structure only, and support a single conformation model Aa for roxithromycin with two types of hydrogen bonding (II and III). However, conformational averaging of Aa and Ac can give good agreement between theoretical and experimental data for the protonated analogue. The different values of potential energies for the observed low-energy conformers support the importance of hydrogen bonding in macrolide conformation. It appears that intra-residue hydrogen bonding, such as type III, 11-OH///OC (1), plays a role in determining the conformation of a large region [from C(9) to C(1)] of the antibiotic macrolide. Roxithromycin probably exists in the form of two ring-conformers ‘AII⇔AIII’ and, in CDCl3, a hydrogen bridge is formed that lowers the barrier enough to make interconversion possible.

13C NMR Chemical Shift Assignments in Dibucaine and Dibucaine Hydrochloride Determined by Two-Dimensional NMR Spectroscopy

Abstract 13C NMR chemical shift assignments were obtained for dibucaine in CDCl3 and dibucaine hydrochloride in D2O solution using one-bond and long-range two-dimensional heteronuclear correlation techniques. The 13C chemical shift assignments, together with the fully coupled 13C spectrum, allowed the measurement of one-bond, and long-range 13C1H coupling constants.

Use of two-dimensional spectroscopy for the determination of the stereochemical structure of 3-carbethoxy-2-methyl-7a-(4-carbethoxy-5-methyl-2-furyl)-3a,4,5,6,7,7a-hexahydrobenzofuran

Homo- and heteronuclear two-dimensional correlation spectra, as well as J-resolved spectra with selective excitation, were used to analyze in detail the stereochemical structure of 3-carbethoxy-2-methyl-7a-(4-carbethoxy-5-methyl-2-furyl)-3a,4,5,6,7,7a-hexahydrobenzofuran, obtained by the reaction of cyclohexenyl-acetylene with acetoacetic ester in the presence of a manganese(III) salt. It was shown that the use of the long-range 13C-1H coupling constants is a very effective method for the determination of the conformation of the molecule. The stereochemical aspects of the reaction of cyclohexenylacetylene with acetoacetic ester is discussed.

Conformational study of substituted methyl phenyl sulphoxides. A multinuclear (1H, 13C, and 17O) approach

A number of ring-substituted methyl phenyl sulphoxides have been examined with a multinuclear n.m.r. approach in order to obtain experimental evidence of the conformational properties of the methylsulphinyl group bonded to an aromatic ring. Measurements were performed of 1H, 13C, and 17O chemical shifts and LIS (lanthanide-induced shifts) on 1H and 13C, long-range 13C–1H coupling constants. Each of these approaches by itself is not fully conclusive in showing the orientation of the SO bond in the different compounds examined, but by using them in combination a sound picture of the conformational behaviour of these molecules in solution can be obtained. The SO bond is thus almost coplanar with the aromatic ring in ortho-substituted compounds and oriented in the opposite direction with respect to the substituent. The twist-angle probably differs slightly as a function of the ortho-group. An increasing degree of distortion from coplanarity is found in para-substituted derivatives and ortho-disubstituted compounds. As regards 17O chemical shifts, these were found to span a smaller range than in the corresponding acetophenones.

An analysis of the 1H and 13C nuclear magnetic resonance spectra of 3-t-butylaminoacrolein and of glyoxal t-butylhydrazone

1 H N.m.r. spectra have confirmed that 3-t-butylaminoacrolein exists as the E-s-E configuration in polar solvents, and as a mixture of Z-s-Z and E-s-E isomers in non-polar solvents. The spectra of glyoxal t-butylhydrazone are independent of solvent and are thought to indicate Z-s-E structure for this compound. The fully coupled 13C n.m.r. spectra of both compounds have been completely assigned using specifically labelled derivatives where necessary. The long-range 13C–1H coupling constants of 3-t-butylaminoacrolein are strongly dependent on the shape of the conjugated system.

Complete analysis of the high-resolution proton coupled carbon-13 NMR spectra of toluene

High-resolution, 25.16 MHz, proton coupled 13C Fourier transform NMR spectra of the natural abundant 13C-toluenes have been obtained and completely analyzed. Signs and accurate magnitudes of all possible 13C 1H coupling constants in toluene as well as 1H chemical shift differences, including long-range 13C isotope shifts, could be determined from the analysis of these complex spectra. The unperturbed relative 1H chemical shifts of toluene containing only 12C carbons and the long-range 13C isotope effects on these shifts have been calculated from the latter data. Finally, the signs and magnitudes of the long-range 13C 1H coupling constants are discussed with respect to the 1H 1H couplings in toluene and other model compounds. Special attention has been paid to the δ-π exchange polarization mechanism for π-electron couplings.