Conformational analysis of cyclic terpenes: application of computational and experimental (NMR) methods

The solution structure of the cyclic diterpene cembrene was investigated. A strategy for conformational analysis is proposed which is based on computational and experimental (NMR) methods. By a non-systematic, random exploration of torsional angles under ring-closing constraints a search for favourable low-energy conformers is accomplished and their energy is minimized. According to several criteria of equality, groups of “equal” structures are formed. Steady-state nuclear Overhauser effects and vicinal coupling constants are calculated for the group representatives. For the evaluation of the most probable solution structure, which is based on these parameters, rather than the structures themselves, calculated and experimentally determined values are compared. As a result the conformer which corresponds to the lowest energy structure proposed by computational methods alone fits best with experimental parameters and strongly dominates the solution structure of cembrene.