Heteronuclear COSY spectra

Figure 3.22 Pulse sequence used to produce 1H-I3C heteronuclear COSY spectrum. (Adapted with permission of Nelson Thornes Ltd. from Figure 8.9 of Akitt, J. W. NMR and Chemistry, 3rd ed., 1992.)...

Figure 3.16 Pulse sequence used to produce a heteronuclear COSY spectrum.

Figure 6.11 A 3D heteronuclear HMQC-COSY spectrum of a tripepiide. The o),-axis represents N chemical shifts, whereas the (Or and 88, copyright (1988), with permission from Academic Pre.ss, Inc.)...

Figure 58(b) shows a COSY spectrum of DP9 as a representative example of XH chemical shifts that were readily assigned from the doublet at 65.38 (J = 14.4 Hz) corresponding to the C-l proton. Heteronuclear (HETCOR) 13C-XH spectroscopy allowed indirect assignment of the 13C chemical shifts. The assignment of all chemical shifts and calculated charge densities for anions DP1-DP13 is presented in Table 4868. 

The HSC spectrum is the heteronuclear analogue of the COSY spectrum and identifies which protons are coupled to which carbons in the molecule. The HSC spectrum has the NMR spectrum of the substance on one axis (F2) and the i C spectrum (or the spectrum of some other nucleus) on the second axis (Fi). A schematic representation of an HSC spectrum is given below. It is usual to plot a normal (one-dimensional) H NMR spectmm along the proton dimension and a normal (one-dimensional) C NMR spectmm along the C dimension to give reference spectra for the peaks that appear in the two-dimensional spectmm. 

Multidimensional NMR spectra are not restricted to cases where the separate frequency axes encode signals from different nuclear types. Indeed, much of the early work on the development of 2D NMR was performed on cases where both axes involved chemipal shifts. The main value in such spectra comes from the information content in cross peaks between pairs of protons. In COSY-type spectra (COSY = Correlation SpectroscopY) cross peaks occur only between protons that are scalar coupled (i.e., within 2 or 3 bonds) to each other, whereas in NOESY (NOE Spectroscopy) spectra cross peaks occur for protons that are physically close in space (<5 A apart). A combination of these two types of 2D spectra may be used to assign the NMR signals of small proteins and provides sufficient information on internuclear distances to calculate three-dimensional structures. Figure 12.3 includes a panel showing the COSY spectrum of cyclosporin and highlights the relationships between ID H-NMR spectra and corresponding 2D homonuclear (COSY) and heteronuclear (HSQC) spectra. 

As shown in the list of relay COSY experiments heteronuclear correlation experiments are possible. In Check it 5.4.1.14 the H-H-X relay IR, DC COSY experiment for the crotonaldehyde type spin system is calculated. Implementing a relay step to a heteronucleus enables complex IR COSY spectrum to be disentangled by including a heteronuclear polarization transfer to link the IR signals to the heteronuclear chemical shift dimension. Fig. 5.26 illustrates this schematically for two spin systems. Since 8(Ra) = 5(Rd) and 5(Rt>) = 5(Rg) at least two IR, IR relay cross peaks which belong to two different relayed spin systems overlap in the IR, IR spectrum. Rowever because 5(Cc) 4 5(Cf) these peaks may be separated if the correlation peaks can be related to the heteronucleus which has a different chemical shift for each peak. 

Correlations between H and 13C nuclei via scalar couplings can be shown by two-dimensional COSY spectra (4-6). This is exemplified by a heteronuclear (]H,3C) COSY spectrum of 7-methoxycoumarin (B7-4, hemiarin) shown in Fig. 3a (bottom). The cross-peaks connect the signals of hydrogen and carbon atoms directly attached. 

Navelbine . The most recent application of inverse-detected 2D NMR methods to a bis-indole was the reported assignment of the proton and carbon NMR spectra of Navelbine (24) reported by the authors (Spitzer et al. 1992). Direct proton-carbon shift correlations were established using an HMQC spectrum. The authors also reported the comparative evaluation of the recently reported GEM-COSY technique (Domke et al. 1991), which affords a heteronuclear correlation spectrum of only the methylenes of a molecule, with the HMQC spectrum. Based on their assessment, GEM-COSY, while useful, did not offer any advantage over the HMQC experiment. In addition, the nature of the experiment required high levels of... 

Fig. 2.43 a. Contour plot of the homonuclear COSY spectrum (HOMCOR) of rhizobactin (42) revealing the coupling connectivities of the four separate units that compose the molecule plus an impurity b contour plot of the heteronuclear COSY (HECTOR) showing carbon and proton assign-... 

A new form of heteronuclear relayed coherence transfer spectroscopy has recently been described which can establish H-X-H connectivities directly. The pulse sequence employed is shown in Figure 5.89. A P-relayed COSY spectrum of triethylphosphonoacetate is shown in Figure 5.90. Protons A and B are both coupled to a common P nucleus and this connectivity is clearly indicated by the P-relayed COSY spectrum. 

A H(detected)- C shift correlation spectrum (conmion acronym HMQC, for heteronuclear multiple quantum coherence, but sometimes also called COSY) is a rapid way to assign peaks from protonated carbons, once the hydrogen peaks are identified. With changes in pulse timings, this can also become the HMBC (l eteronuclear multiple bond coimectivity) experiment, where the correlations are made via the... 

A second 2D NMR method called HETCOR (heteronuclear chemical shift correlation) is a type of COSY in which the two frequency axes are the chemical shifts for different nuclei usually H and With HETCOR it is possible to relate a peak m a C spectrum to the H signal of the protons attached to that carbon As we did with COSY we 11 use 2 hexanone to illustrate the technique... 

The matrix obtained after the F Fourier transformation and rearrangement of the data set contains a number of spectra. If we look down the columns of these spectra parallel to h, we can see the variation of signal intensities with different evolution periods. Subdivision of the data matrix parallel to gives columns of data containing both the real and the imaginary parts of each spectrum. An equal number of zeros is now added and the data sets subjected to Fourier transformation along I,. This Fourier transformation may be either a Redfield transform, if the h data are acquired alternately (as on the Bruker instruments), or a complex Fourier transform, if the <2 data are collected as simultaneous A and B quadrature pairs (as on the Varian instruments). Window multiplication for may be with the same function as that employed for (e.g., in COSY), or it may be with a different function (e.g., in 2D /-resolved or heteronuclear-shift-correlation experiments). 

The H-NMR and C-NMR chemical shifts have been assigned and substractures have been deduced on the basis of COSY-45° (Problem 5.13) and other spectroscopic observations. Interpret the HMBC spectrum and identify the heteronuclear long-range coupling interactions between the H and C nuclei. 

C-NMR, COSY, HMQC (heteronuclear multiple quantum coherence), and HMBC (heteronuclear multiple bond correlation).48 Furthermore, the structure of trimer was confirmed by X-ray crystallography.48 The incorporation of 13C into the indole 3a position proved valuable in these structural determinations and in documenting the ene-imine intermediate. For example, the presence of a trimer was readily determined from its 13C-NMR spectrum (Fig. 7.7). 

Gelsevirine (2) was first isolated in 1953 from G. sempervirens as a minor component (3). Its structure was later elucidated on the basis of mass spectrometry as well as H-NMR and 13C-NMR studies (4). Gelsevirine has been found to be the predominant alkaloid in G. rankinii (24), and it was claimed that some of the previously reported 1 H-NMR and 13C-NMR data should be revised. Thus the previous assignments of H-16, H-15, H-14a, H-14e, and H-6 for gelsevirine should be changed to H-15, H-14a, H-16, H-6, and H-14e, respectively, from the evidence of the more accurate homonu-clear 2D COSY experiments. Similarly, from the heteronuclear 2D correlation spectrum, the assignments for C-16, C-15, C-6, and 1V-CH3 should be revised to C-15, C-16,1V-CH3, and C-6, respectively. 

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