Chapter 9: Nuclear Magnetic Resonance Experiments Applicable to the Elucidation and Characterization of Alkaloid Structures Part I: Direct ¹H–¹³C Heteronuclear Shift Correlation and Establishing Contiguous Protonated Carbon Spin Systems

Characterization of alkaloid structures begins with the preparation of the sample, which is discussed first, followed by probe and parameter choices. In parallel, it is assumed that an investigator will also acquire mass spectral data to help define the empirical formula of the molecule. A proton reference spectrum initiates the pursuit of the structure of the molecule. If there is sufficient material available, a 1D ¹³C spectrum might also be acquired at that time. The variants of acquiring an HSQC heteronuclear shift correlation spectrum are discussed, including multiplicity editing and what are generally referred to as pure shift HSQC spectra. In sample-limited situations, investigators may wish to consider intentionally folding their heteronuclear shift correlation spectra into the second or F₁ frequency domain, which is considered next, followed by non-uniform sampling. Both of these techniques can lead to considerable savings of spectrometer time. Next, we favor the acquisition of long-range heteronuclear shift correlation data to supplement the HSQC spectrum. In sample-limited situations, where there is insufficient material to allow for the convenient acquisition of a ¹³C reference spectrum, the acquisition of HMBC data can provide access to non-protonated carbon resonances that would otherwise be derived from a carbon reference spectrum. Beyond this array of experiments, the authors generally undertake defining the proton–proton connectivity network using COSY or TOCSY spectra. In many cases, the ensemble of data described in this chapter will be sufficient to define the structure of the molecule in question.