Efficient Access to Elusive 1D ¹³C NMR Spectra through Highly Resolved ¹H, ¹³C-Long-Range Correlation Spectroscopy

A method for obtaining 1D ¹³C NMR spectra from natural products or metabolites using proton detection is described. The approach delivers singlets for every ¹³C signal without conducting any broadband ¹H decoupling (CPD) and is based on calculating ¹³C projections from constant-time HMBC and conventional HSQC experiments, recorded at high digital resolution and processed to pure phases. Paramount to the proposed method is the implication of nonuniform sampling and echo processing. The echo processing produces phase-sensitive 2D CT-HMBC spectra with narrow ¹³C signal line shapes. Two simple HMBC pulse sequences are utilized with the suppression of homo- and heteronuclear couplings. Due to the removal of the ¹H multiplet structure in F₁ (no tilt at higher digital resolution), ¹³C singlets arise. An overall increase in ¹³C signal-to-noise (SINO) for all types of carbon multiplicities is observed, making the proposed technique superior compared to direct ¹³C excitation. For otherwise difficult-to-measure quaternary carbon atoms, a SINO enhancement of up to 6 and 12 depending on F₁ resolution (3 and 6 Hz/point) is reported. Echo/anti-Echo signal detection cleans up the spectrum. Nonuniform sampling (NUS) lays the groundwork to significantly reduce the total acquisition time. Final 1D ¹³C projections are obtained by combining the ¹³C projection from CT HMBC and conventional HSQC. This orthogonal concept of combining the ¹³C projections from different spectra inherently minimizes the risk of missing ¹³C cross-peaks by inappropriate setting of long-range ⁿJ_HC coupling delays and the shortcoming of T₂ relaxations. The advantages and some limitations of the concept are discussed.