Structure Determination of Natural Products by Mass Spectrometry

Abstract

I review laboratory research on the development of mass spectrometric methodology for the determination of the structure of natural products of biological and medical interest, which I conducted from 1958 to the end of the twentieth century. The methodology was developed by converting small peptides to their corresponding polyamino alcohols to make them amenable to mass spectrometry, thereby making it applicable to whole proteins. The structures of alkaloids were determined by analyzing the fragmentation of a known alkaloid and then using the results to deduce the structures of related compounds. Heparin-like structures were investigated by determining their molecular weights from the mass of protonated molecular ions of complexes with highly basic, synthetic peptides. Mass spectrometry was also employed in the analysis of lunar material returned by the Apollo missions. A miniaturized gas chromatograph mass spectrometer was sent to Mars on board of the two Viking 1976 spacecrafts.

Beyond the paradigm: Combining mass spectrometry and nuclear magnetic resonance for metabolomics

“…In the case of NMR, the development of microcoils, microflow and cyroprobes have significantly improved the dynamic range and sensitivity of NMR and have thus greatly benefited the structural characterization of sample-limited natural products and metabolites [106-108]. Mass spectrometry has made similar advancements that have also benefited natural products chemistry and metabolomics by developing high-resolution mass spectrometers and tandem MS-MS methods to improve the accuracy and ease of structure elucidation [109-113]. …”

Two-dimensional mass spectrometry: new perspectives for tandem mass spectrometry

“…In addition to measuring the m / z ratio of compounds, mass spectrometers can also be used to fragment them to elucidate their chemical structure (tandem mass spectrometry) (Biemann 2015 ). Current fragmentation methods focus mainly on interactions with neutral particles, photons, and electrons.…”

Structure elucidation of metabolite x17299 by interpretation of mass spectrometric data

“…Although mass spectrometry has historically played a significant role in the structural elucidation of small compounds, especially before the availability of NMR spectroscopy (Biemann 2015; Wright and Warren 1967), only a small number of structures of natural products have been deduced solely by mass spectrometry and later confirmed by chemical synthesis (Dickschat 2014; Schiestl et al 2003). As shown in textbooks, a fragmentation spectrum usually contains abundant structural information that can be harnessed for structural elucidation of the example compound.…”