1H-Detected IPAP DEPT-INADEQUATE and IPAP RINEPT-INADEQUATE for the measurement of long-range carbon-carbon coupling constants

The sensitivity of cryoprobes, which are rapidly becoming available, have brought about the possibility of measurement of 13C, 13C coupling constants at the natural abundance of 13C using tens rather than hundreds of milligrams of compounds. This relatively recent development lays the foundation for a more routine use of the 13C, 13C long-range coupling constants in the conformational analysis of molecules. We have designed novel 1H-detected INADEQUATE experiments optimized for long-range 13C, 13C correlations and the measurement of long-range coupling constants. These experiments incorporate refocusing of 1JCH coupling constants prior to the formation of DQ coherences and 1H-decoupling during the long carbon-carbon evolution intervals. Such modifications significantly enhance their performance over 1H-detected INADEQUATE experiments currently in use for mapping the one-bond 13C, 13C correlations. 1H or 13C polarization is used a starting point in long-range correlation 1H-detected IPAP DEPT-INADEQUATE or RINEPT-INADEQUATE experiments. These correlation experiments were modified yielding in-phase (IP) or antiphase (AP) 13C, 13C doublets in F1. Procedures were developed for their editing yielding accurate values of small 13C, 13C coupling constants. The methods are illustrated using mono- and disaccharide samples and compared with related 13C-detected experiments by means of the measurement of interglycosidic 13C, 13C coupling constants of a disaccharide.