Anisotropic NMR Methods: Orthogonal Verification of Novel and Complex Natural Product Structures

Abstract

Complex natural products, particularly those with no structural precedent, represent an area of investigation with vast possibilities for spectral misassignment and the intrusion of investigatory bias. The myriad of two-dimensional NMR experiments now available allow researchers to tackle increasingly more complex structures, but unfortunately also seem to have opened new doors to data misinterpretation, as evidenced by the numbers of misassigned structures burgeoning in the past decade. Orthogonal structural verification using anisotropic NMR methods, including residual dipolar coupling (RDC) and residual chemical shift anisotropy (RCSA), offers a powerful means of confirming or refuting a proposed structure without the intrusion of investigatory bias. In this chapter, we provide a coherent theoretical framework of key concepts, an overview of recent status and trends, followed by detailed discussion on some noteworthy methods, a number of first-hand examples and a thorough survey of natural products characterized by anisotropic NMR in the published literature, and finally an introduction to methods related to the challenging but not uncommon cases of conformationally flexible molecules. We hope this chapter contributes to wider adoption of anisotropic NMR in natural product research and helps to quell the wave of misassigned structures in the chemical literature.