Connecting discrete stereoclusters by using DFT and NMR spectroscopy: the case of nivariol.

The structural determination of small organic molecules is mainly undertaken by using NMR techniques, although it is increasingly supplemented by using computational methods. NMR parameters, such as chemical shifts and coupling constants, are extremely sensitive indicators of local molecular conformation and are a source of structural evidence. However, their interpretation is fairly challenging in many circumstances, such as the case of the new polyether squalene derivative nivariol, the structure of which was elucidated by means of NMR spectroscopy and DFT calculations. The potential flexibility of this molecule and the high number of quaternary carbon atoms that it contains make its configurational assignment very difficult. Moreover, the relative configuration of four separated stereoclusters was established and subsequently connected by using NOE and J-based analysis, as well as by a comparison of its experimental (13)C NMR chemical shifts with the corresponding population-weighted values, as calculated by using DFT methods. Limitations of these used approaches became apparent but were overcome by combining the two methods.