The most significant new techniques that have been used in the twenty-first century for the structure elucidation of sesquiterpenes and some derivatives are reviewed in this chapter. A distinctive feature of these methodologies is the combination of accurate experimental measurements with theoretical data obtained by molecular modeling calculations that allow to visualize, understand, and quantify many structural characteristics. This has been the case for NMR spectroscopy, which has expanded its potential for solving complex structural problems by means of comparison with quantum mechanical molecular models. Ab initio and density functional theory calculations of chemical shifts, coupling constants, and residual chemical shift anisotropies have played important roles in the solution of many structures of sesquiterpenes. The assignments of their absolute configurations by evaluation of calculated and experimental chiroptical properties as electronic and vibrational circular dichroism are also reviewed. This chapter also includes the use of X-ray diffraction analysis with emphasis on calculations of the Flack and Hooft parameters, which are applicable to all molecules that crystallize in non-centrosymmetric space groups. The accurate molecular models of sesquiterpenes, validated by concordance with their experimental properties, are nowadays essential for the interpretation of the effects of these natural products on biological systems.
Keywords: Chiroptical properties; Molecular modeling; NMR spectroscopy; Quantum mechanical calculations; Sesquiterpenes; Structure elucidation; X-ray diffraction.