Conformational analysis of a seven-membered ring azasugar, (3R,4R,6S)-trihydroxyazepane: Comparison of GIAO calculation and experimental NMR spectra on ¹³C chemical shifts

DFT/B3LYP/6-311++G(d,p) calculation of the relative stable conformations of (3R,4R,6S)-trihydroxyazepane are presented. The GIAO/DFT/OPBE, GIAO/DFT/B3LYP and GIAO/HF single point calculations with 6-311++G(d,p), 6-311+G(2d,p), cc-pVDZ and cc-pVTZ basis sets of (3R,4R,6S)-trihydroxyazepane were conducted to generate their ¹³C NMR chemical shifts. According to calculation results, 14 (3R,4R,6S)-trihydroxyazepane with optimized structure were generated. There were three conformers which contain the intramolecular hydrogen bonding exhibit a lowest electronic energies and TCN1(eq) was the most stable conformer than others. Boltzmann weighting factor analysis exhibits that TCN1(eq), TCN3(eq) and TCN5(eq) dominate a major contribution among the 14 conformers. The individual calculated NMR results of TCN1(eq), TCN3(eq) and TCN5(eq) represents a quite close correlation with experimental data. Moreover, the experimental ¹³C NMR chemical shifts gave only the average contribution of all conformers. In our investigation, the calculated ¹³C NMR chemical shifts of mixture (3R,4R,6S)-trihydroxyazepane exhibit a good agreement with the experimental NMR data. Calculated NMR results of mixture (3R,4R,6S)-trihydroxyazepane conformers display a remarkable MAE and RMS improvement over that of each individual conformer. A good calculation method and basis set choice to evaluate the theoretical chemical shifts for these conformers is HF/cc-pVTZ.