Nuclear Magnetic Resonance Experiments Applicable to the Elucidation and Characterization of Nitrogenous Natural Products: 1H-15N Heteronuclear Shift Correlation Methods

Aside from carbon and hydrogen, the next most prevalent elements incorporated into the structures of natural products are nitrogen and oxygen. Fortunately,¹⁵N is a spin ½ nuclide that is present at 0.37% natural abundance and is accessible by modern, indirect detection nuclear magnetic resonance (NMR) techniques. Prior to the advent of indirect detection,¹⁵N NMR studies were extremely challenging and relatively seldom reported for natural products. That began to change in the early 1990s through the pioneering work of laboratories in the USA and Japan, and by the latter half of that decade, this had become an active area of NMR investigation, with numerous applications to natural products being reported annually. Initially, all of the work being reported relied on¹H–⁵N HSQC or HMBC methods. Around 2000, a number of new NMR methods applicable to long-range¹H–¹⁵N shift correlation began to appear. There is now a range of experiments that, when coupled with cryogenic NMR probe technology, make it feasible to undertake¹H–¹⁵N studies successfully with sub-milligram samples of material. Considerations implicit in the acquisition of¹H–¹⁵N heteronuclear shift correlation data are discussed. The range of methods currently available is reviewed and examples are shown. Strychnine and cyclosporine are employed as model compounds in order to illustrate the applications of the techniques, which will provide readers with reference data to assist them in implementing these experiments in their own laboratories.