Application of liquid chromatography-nuclear magnetic resonance spectroscopy to the identification of natural products

LC-NMR combines the separation power of high-performance liquid chromatogra phy (HPLC) with the superior structural information content of nuclear magn etic resonance (NMR). These two techniques traditionally have been the prim ary tools used by natural products chemists to isolate and determine the st ructures of molecules of interest. Recent advances in NMR technology have a llowed the practical application of LC-NMR, thus providing natural products chemists with a hyphenated technique which combines the two most important tools in their field. A brief review of the literature describing how LC-N MR has been applied to natural products research is followed by a specific example illustrating how this technique was used to identify the marine alk aloid aaptamine (1). Aaptamine was identified as the active component in th e crude dichloromethane extract of the sponge Aaptos sp. which had been det ermined to possess inhibitory activity against the enzyme glutamine:fructos e-6-phosphate amidotransferase (GFAT) by a high throughput screening (HTS) effort. Isolated aaptamine (1) exhibited an IC50 = 120 muM against this enz yme. The experience gained from the identification of aaptamine was used to define a strategy for the use of LC-NMR in a natural products HTS program. (C) 2000 Elsevier Science B.V. All rights reserved.