Chapter 10 - Assignment of Regio- and Stereochemistry of Natural Products Using Mass Spectrometry Chlorogenic Acids and Derivatives as a Case Study

Abstract

Abstract Structural assignment of natural products has for decades been the prerogative of NMR spectroscopy. In particular, unambiguous assignment of aspects of regio- and stereochemistry in complex natural product structures has on numerous occasions been shown to be a unique strength of NMR spectroscopy. In contrast, for decades mass spectrometry has been prejudicially considered to be isomer blind. Recent advances have, however, clearly demonstrated that certain mass spectrometric techniques are able to clearly distinguish between isomeric compounds and also that an in-depth understanding of fragmentation processes leads to surprising levels of structure assignment confidence. In comparison to NMR spectroscopy, mass spectrometry offers a variety of obvious advantages in natural product chemistry including enhanced sensitivity; ease of coupling to separation techniques, in particular liquid chromatography; and the ability to isolate individual ions from a complex mixture in the gas phase. Hence, especially for complex samples containing natural products as minor constituents, structure elucidation by mass spectrometry constitutes the only practical access to natural product structures. Within the chapter, we review mass spectrometric methods currently employed to assign isomeric structures including tandem mass spectrometry, energy-resolved mass spectrometry, and ion mobility mass spectrometry applied to natural product research. The advantages, practical implications, limitations, and future prospects of the methods are discussed. In the next section, we review selected classes of natural products in which successful structure elucidation by mass spectrometry has been demonstrated. We limit ourselves to the discussion of representative examples in which MS data lead to definite unambiguous structure assignment. Examples from the literature include chlorogenic acids, quinic and shikimic acid derivatives, proanthocyanidins, hydroxylactones, sulfated saccharides, phenolic acid esters of carbohydrates, and polyketides. This chapter is organized in a tutorial style, allowing other researchers to employ these methods in their own research.