LC/NMR in Natural Products Chemistry

Abstract

Efficient detection and rapid characterisation of natural products play an important role for their study in complex biological matrices such as crude plant extracts. Their preliminary identification at the earliest stage of separation is a strategic element for guiding selective isolation procedures. Hyphenated techniques such as high performance liquid chromatography (HPLC) coupled to UV and mass spectrometry (LC/UV/MS) have proved to be extremely useful in combination with biological screening for a rapid survey of natural products. However, these coupled techniques do not allow a full on-line identification, except for some well-known natural products, and complementary on-line spectroscopic information is needed. Thus, HPLC coupled to nuclear magnetic resonance (LC/NMR) represents a potentially interesting complementary technique to LC/UV/MS for detailed on-line structural analysis. Indeed recent progress in NMR technology has given a new impulse to LC/NMR which is now emerging as a powerful analytical tool. The development of efficient solvent suppression techniques enables the measurement of high quality LC/<sup>1</sup>H-NMR spectra, both on-flow and stop-flow, with reversed-phase HPLC conditions. Non-deuterated solvents such as MeOH or MeCN can be used, while water is replaced by D<sub>2</sub>O. In this review, a summary of the basic principles and modes of operation of LC/NMR are briefly described. Selected examples of LC/NMR analyses of natural products in crude p lant extract o r in enriched fractions are presented. They include different ways of using this technique. An overview of the relatively scarce applications with natural products is given. The potential and the limitations of LC/NMR in conjunction with LC/UV/MS for the on-line analysis of plant metabolites are discussed.