¹J_CC‐edited HSQC‐1,n‐ADEQUATE: a new paradigm for simultaneous direct and long‐range carbon–carbon correlation

Abstract

Establishing the carbon skeleton of a molecule greatly facilitates the process of structure elucidation, leaving only heteroatoms to be inserted, heterocyclic rings to be closed, and stereochemical features to be defined. INADEQUATE, and more recently PANACEA, have been the only means of coming close to the goal of totally defining the carbon skeleton of a molecule. Unfortunately, the extremely low sensitivity and prodigious sample requirements of these experiments and the multiple receiver requirement for the latter experiment have severely restricted the usage of these experiments. Proton-detected ADEQUATE experiments, in contrast, have considerably higher sensitivity and more modest sample requirements. By combining experiments such as 1,1-ADEQUATE and 1,n-ADEQUATE with higher sensitivity experiments such as GHSQC through covariance processing, sample requirements can be further reduced with a commensurate improvement in the s/n ratio and F(1) resolution of the covariance processed spectrum. We now wish to report the covariance processing of an inverted (1)J(CC) 1,n-ADEQUATE experiment with a non-edited GHSQC spectrum to afford a spectrum that can trace the carbon skeleton of a molecule with the exception of correlations between quaternary carbons.

Application of 1,n-ADEQUATE and Modified Variants to Structure Elucidation and Spectral Assignment Problems

“…In the course of acquiring an inverted 1 J CC 1,n-ADEQUATE optimized for 1 J CC = 40 Hz and n J CC = 5 Hz, it was noted that the C21-C22 1 J CC correlation had strong positive phase rather than being inverted as intended. 17 The C21-C22 1 J CC coupling constant is 71.8 Hz. 26 Comparing the measured coupling constant to the amplitude transfer curve shown in Figure 8a, the positive response of the 1 J CC C21-C22 correlation is not surprising as that coupling is consistent with one of the positive lobes of the amplitude transfer curve.…”

“…23,37,55 -58 Ultimately, perhaps the most promising outcome of this research is reflected in the covariance processing combination of an unedited HSQC spectrum with an inverted 1 J CC 1,n-ADEQUATE spectrum. 17 Before discussing that pairing of experiments, it is germane to step back and first consider combining HSQC and 1,1-ADEQUATE spectra with covariance processing.…”

“…17 The data content of what can be termed as a 1 J CC -edited HSQC-1,n-ADEQUATE spectrum is an amalgamation of the preceding two types of experiments with editing based on 1 J CC vs n J CC coupling. Consider 15 as a hypothetical model structural fragment.…”

“…To date, there has only been the initial example of a 1 J CC -edited HSQC-1,n-ADEQUATE spectrum, which was calculated using single optimization 1 J CC / n J CC 40/7 Hz data for strychnine (11) 17 and the recent study of coniothyrione (13) 49 reported. The 1 J CC -edited HSQC-1,n-ADEQUATE spectrum of strychnine is shown in Figure 16.…”

“…Figure 16. 17 Diagonally symmetric correlations between protonated carbon pairs ( 1 J CC correlations) are inverted and plotted and labeled in red. Correlations are again labeled using the convention δF 2 − δF 1 .…”