Electrospray Ionization Tandem Mass Spectrometry as a Tool for the Structural Elucidation and Dereplication of Natural Products: An Overview

Abstract

Natural products (NPs) obtained from plants and microorganisms often exhibit biological activities of interest for the discovery of new drugs as well as pharmaceutical and agrochemical products (Fredenhagen et al., 2005; Konishi et al., 2007; Lang et al., 2008). For instance, over 60% of the anticancer drugs have been discovered directly from NPs or are semi-synthetic derivatives of these compounds (Butler, 2008; Costa-Lotufo et al., 2010; Harvey, 2008; Newman & Cragg, 2007). However, the research for new bioactive compounds is usually laborious and slow, once the biological evaluation processes are preceded by isolation, purification, and structural elucidation steps, which are usually expensive and time-consuming (Konishi et al., 2007). This fact, in combination with the large number of known compounds, has led the scientific community to develop new techniques for the direct identification of NPs from extracts and natural broths, thus avoiding reisolation of already known compounds (Bindseil et al., 2001; Konishi et al., 2007; Lee, 2004; Newman et al., 2000; Newman et al., 2003; Shu, 1998). Dereplication is the process that allows for the rapid identification of bioactive metabolites in crude extracts by distinguishing previously identified compounds from novel ones (Crotti et al., 2006). This technique avoids repetitive work of isolation of already known NPs (Wolf & Siems, 2007), promoting chemical screening or metabolite profiling (Crotti et al., 2006). The dereplication process involves separation of single metabolites by chromatographic methods, identification of these compounds by spectroscopic methods, bioassays for evaluation of the biological activity, and searches in databases for verification of the novelty of these compounds (Konishi et al., 2007; Wolf & Siems, 2007). Hyphenated techniques have played a key role in the identification of NPs and other organic compounds (Crotti et al., 2006; Prasain et al., 2003). These techniques combine a separation method (i.e., gas chromatography, GC; liquid chromatography, LC) with a structural identification technique (i.e., mass spectrometry, MS; ultraviolet-visible spectroscopy, UV-vis; nuclear magnetic resonance, NMR). Although a number of