254
J. C. Pardo-Novoa and C. M. Cerda-García-Rojas
1 Introduction
Throughout the history of Chemistry, a series of techniques has been developed to
decipher the molecular structure of new compounds of natural origin, starting from
chemical degradation up to highly sophisticated NMR methodologies in combination with quantum mechanical calculations of their spectroscopic properties. This
contribution reviews the most relevant techniques that have been used recently in
determining the structure of a group of representative natural products such as the
sesquiterpenes. Essentially, the papers dating back to this new century will be referenced from January 2001 until May 2020. A frequent characteristic of these new
methodologies consists of the combined use of precise experimental determinations
and accurate theoretical data obtained by molecular modeling calculations for a property of a given compound. This has been particularly valuable for nuclear magnetic
resonance (NMR) spectroscopy that has expanded its potential for solving complex
structural problems. At this time, it is possible to say that if the structure of a studied
new compound is correct, its calculated data will easily match with the experimental
ones, thus validating the structural hypothesis for a given molecule.
Some other lines of research on sesquiterpenes, particularly those dedicated to the
determination of their absolute configuration, involve the comparison of calculated
and experimental chiroptical properties, namely, electronic and vibrational circular
dichroism as well as the use of X-ray diffraction analysis with emphasis on calculation
of anomalous dispersion effects, as applicable to all organic molecules that crystallize
in non-centrosymmetric space groups, not only to those containing “heavy” atoms.
Although many investigations described in this chapter utilize more than one modern
technique for the structure elucidation of isolated molecules, they are discussed in
the section that is considered as the most pertinent and illustrative for each case.
2 Techniques Based on NMR Spectroscopy
The power of NMR spectroscopy has been enhanced greatly by its combination with
theoretical parameters calculated using quantum mechanics mainly with Density
Functional Theory (DFT) and Hartree–Fock (HF) protocols. In most cases, the calculated
1 H and
13 C chemical shifts and coupling constants (J) are compared with the
experimental values by means of basic statistical analysis allowing the determination of the correct configuration among several structural hypotheses. Other strategies include the measurement of residual dipolar couplings that generate information
about the orientations between internuclear vectors, in correlation with the molecular
three-dimensional arrangement of a structure. This section also comprises the review
of modified Mosher methods in NMR tubes that allow the use of small amounts of
materials and the combination of this methodology with molecular models for the
evaluation and visualization of the diamagnetic shielding effects present in the ester
derivatives. Several articles about the use of cryoprobes that have enhanced the power
J. C. Pardo-Novoa and C. M. Cerda-García-Rojas
1 Introduction
Throughout the history of Chemistry, a series of techniques has been developed to
decipher the molecular structure of new compounds of natural origin, starting from
chemical degradation up to highly sophisticated NMR methodologies in combination with quantum mechanical calculations of their spectroscopic properties. This
contribution reviews the most relevant techniques that have been used recently in
determining the structure of a group of representative natural products such as the
sesquiterpenes. Essentially, the papers dating back to this new century will be referenced from January 2001 until May 2020. A frequent characteristic of these new
methodologies consists of the combined use of precise experimental determinations
and accurate theoretical data obtained by molecular modeling calculations for a property of a given compound. This has been particularly valuable for nuclear magnetic
resonance (NMR) spectroscopy that has expanded its potential for solving complex
structural problems. At this time, it is possible to say that if the structure of a studied
new compound is correct, its calculated data will easily match with the experimental
ones, thus validating the structural hypothesis for a given molecule.
Some other lines of research on sesquiterpenes, particularly those dedicated to the
determination of their absolute configuration, involve the comparison of calculated
and experimental chiroptical properties, namely, electronic and vibrational circular
dichroism as well as the use of X-ray diffraction analysis with emphasis on calculation
of anomalous dispersion effects, as applicable to all organic molecules that crystallize
in non-centrosymmetric space groups, not only to those containing “heavy” atoms.
Although many investigations described in this chapter utilize more than one modern
technique for the structure elucidation of isolated molecules, they are discussed in
the section that is considered as the most pertinent and illustrative for each case.
2 Techniques Based on NMR Spectroscopy
The power of NMR spectroscopy has been enhanced greatly by its combination with
theoretical parameters calculated using quantum mechanics mainly with Density
Functional Theory (DFT) and Hartree–Fock (HF) protocols. In most cases, the calculated
1 H and
13 C chemical shifts and coupling constants (J) are compared with the
experimental values by means of basic statistical analysis allowing the determination of the correct configuration among several structural hypotheses. Other strategies include the measurement of residual dipolar couplings that generate information
about the orientations between internuclear vectors, in correlation with the molecular
three-dimensional arrangement of a structure. This section also comprises the review
of modified Mosher methods in NMR tubes that allow the use of small amounts of
materials and the combination of this methodology with molecular models for the
evaluation and visualization of the diamagnetic shielding effects present in the ester
derivatives. Several articles about the use of cryoprobes that have enhanced the power