A program was implemented to prefractionate a large subset of extracts from the Natural Products Repository. This initiative has generated a substantial collection of prefractionated samples (18,000) that are more suited for the high-throughput natural products discovery efforts our laboratory is engaged in. The extract prefractionation library we constructed provides a high-value screening resource for enhanced lead identification in a variety of different assay systems.We have also focused on expansion of our pure natural products library, since this provides the ideal solution to the problems associated with screening extracts. Methods to enhance our structural elucidation capabilities are another major focus of this project, with a special emphasis on techniques used to assign the relative and absolute configuration of unknown natural products. Some of the challenging stereochemical determinations achieved by the group employed diverse methodologies including hydrolysis, derivatization, and liquid chromatography-mass spectrometry analyses, nuclear magnetic resonance (NMR) database comparisons, and circular dichroism (CD) studies. The complete structural elucidation of a novel sponge-derived phosphomacrolide, utilized a combination of micro-scale chiral derivatization and chemical interconversion, with NMR and CD analyses.
