Hyphenated NMR methods in natural products research, part 1: direct hyphenation

This review describes the current status of the development of techniques combining liquid chromatography and nuclear magnetic resonance and their use in the context of natural products. HPLC-NMR methods have a rapidly growing impact on natural products research by enabling structure determination of natural products directly from small amounts of extracts, i. e., prior to the investment in an often lengthy and laborious preparative-scale isolation process. This speeds up extract dereplication and helps to avoid re-isolation of already known extract constituents. Direct HPLC-NMR hyphenation techniques, defined as methods in which NMR spectra are recorded using the HPLC eluate, are described. The recently developed indirect HPLC-NMR method employing an automated solid-phase extraction interface between HPLC and NMR, which replaces the chromatographic solvent with a different solvent for NMR data acquisition, is described in the second part of this review.