Disentangling coupling and NOE pathways involving poorly resolved proton signals: HMQC‐TOCSY and HMQC‐NOESY

Abstract

Abstract COSY and NOESY frequently fail when key proton signals are poorly resolved because of the proximity of the correlating off‐diagonal responses to the diagonal. Proton‐coupled heteronuclear multiple quantum relayed coherence spectroscopy (HMQC–TOCSY) and heteronuclear multiple quantum proton nuclear Overhauser effect (HMQC–NOESY) experiments to circumvent these problems are described. NMR data for a model carbocyclic nucleoside analog are presented for which assignments of resonances and stereochemistry were impossible by ‘conventional’ 2D NMR methods. Resonance and unequivocal stereochemical assignments were made, however, using the HMQC–TOCSY and HMQC–NOESY experiments, respectively.