GHMBC

Another alternative for the interpretation of 1,1-ADEQUATE data is available by overlaying HSQC and 1,1-ADEQUATE spectra. By plotting the two spectra in different colours, as was done in Figure 4, the direct 1H/13C heteronuclear correlation response is visible and provides a guide for interpretation that is sometimes convenient. A further alternative would be to overlay 1,1-ADEQUATE and GHMBC spectra responses appearing in both are identified as 2/ch correlations and all remaining... 

Segments of the aliphatic region of the 8 Hz GHMBC and 60 Hz 1,1-ADEQUATE spectra are shown in Figure 5B. Correlations designated by arrows in the spectrum that appear in both spectra correspond to zJch correlations in the GHMBC data. Other responses in the GHMBC spectrum that do not coincide with responses in the 1,1-ADEQUATE spectrum must therefore arise from "Jch correlations where n > 3. 

Unlike HMBC /GHMBC and related long-range heteronuclear chemical shift correlation experiments, which have hundreds of reported applications in the published literature, there are considerably fewer reported applications of 1,1-ADEQUATE and related long-range variants in the literature. In part, the dearth of reported applications can be attributed to the considerably lower sensitivity of these experiments relative to, for example HMBC/GHMBC. Sensitivity concerns are largely ameliorated,... 

The ADEQUATE data were combined with GCOSY, HSQC, - C, and 1H-15N GHMBC data as input for the COCON CASE program. Four different data sets were prepared as input for the program. Data set A was comprised of the correlations from the GCOSY and 1H-13C GHMBC spectra. Data set B contained the same data as A supplemented by the... 

ADEQUATE correlations. Data set C was comprised of the correlations from the GCOSY, and the - C and 1H-15N GHMBC data. Finally, data set D was comprised of the full ensemble of available 2D correlation data. In the case of bromophakellin (18a), the inclusion of the XH-15N GHMBC data had a slightly greater impact than the inclusion of the... 

Usefully, 1,1-ADEQUATE spectra provide /cc correlations that are equivalent to 2/ch correlations in GHMBC spectra, while 1,/ -ADEQUATE spectra provide 3Jcc correlations that correspond to 4/ch correlations in GHMBC spectra. When these data are combined with GHMBC spectra, which contains predominantly 3/CH correlations, a series of successive... 

Perhaps, the simplest means of approaching the interpretation of an n,l -ADEQUATE spectrum is to compare the observed correlations with those of a GHMBC spectrum acquired with the same /CH optimization. As an example, correlations observed from the H23a/b protons (see 39) in... 

It is interesting to note from even the examination of just the three carbon-carbon correlation pathways from Cl 4, that there is no uniformity in the Jch correlations observed to C14 from the various protons among these correlations. Further, while the observed "/ch correlations are predominantly three-bond correlations, a weak two-bond correlation from H13 to C14 was among the correlations observed. Hence, the h,1-ADEQUATE experiment suffers from the same potential ambiguities of the correlation pathways as the GHMBC experiment. 

A further detractor from the m,n-ADEQUATE experiment is the inherent ambiguity of the two long-range magnetization transfers. As in the HMBC/GHMBC experiment, the m/ci 1 transfer step may afford... 

As shown above, one must first determine the carbon to which the proton long-range correlations are observed. Referring to a GHMBC spectrum will, of course, provide insight into which carbons are... 

Figure 5.3 GHMBC spectrum of a colored impurity formed during the synthesis of Tipranavir. The long-range delay in the experiment was optimized for 10 Hz the data were acquired in 12.5 h. Chemical shift labels show the chemical shift of the carbon to which a given proton is long-range coupled. As can be seen by simple inspection, there was considerable degradation of the sample during the course of the data acquisition as there are peaks in the contour plot corresponding to responses that were not observed in the proton spectrum taken at the outset of data acquisition, which is plotted above the contour plot.

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