Application of 1,1-ADEQUATE and DFT to correct C-13 misassignments of carbonyl chemical shifts for carbapenem antibiotics

Prior to the development of sensitive proton-detected 2D NMR experiments, assigning C-13 signals could be a significant challenge, and mistakes have occurred even for prominent compound classes. In this study, 1,1-ADEQUATE data were used to unambiguously reassign the C-13 chemical shifts for the beta-lactam carbonyl at the C-7 position and the proximal carboxylate at the C-10 position of the carbapenems, meropenem and imipenem. Density functional theory (DFT) was then investigated to provide sufficiently accurate C-13 chemical shift predictions, allowing for the carbonyl signal reassignment of thienamycin.

Automated summary

In this study, C-13 chemical shift of the β-lactam carbonyl at the C-7 position and the proximal carboxylate at the C-10 position in the carbapenems meropenem and imipenem were successfully reassigned using 1,1-ADEQUATE data. Density functional theory (DFT) was employed to accurately predict C-13 chemical shifts, facilitating the reassignment of the carbonyl signal in thienamycin.