Natural products can provide medicinal chemists with a diverse source of bioactive species, either for use as drugs themselves, or for scaffold modifications for further synthetic diversification. However each individual species in a plant is typically present in relatively low concentrations amidst a very complex mixture of other similar species.  Targets are typically selected through the application of various bioassays to crude fractions, followed by intensive analytical work using LC/MS to help identify active species. Supercritical fluid extraction using carbon dioxide often provides a faster cleaner tunable method for efficiently enriching a target natural product compound on a bulk scale, with the removal of more of the interfering plant matrix material as compared to traditional extraction methods, thus providing for simpler chromatography in the subsequent target isolation processes.  Mass directed collection during the first dimension of preparative supercritical fluid chromatography allows for the collection of the desired compound by its target mass from the still very complex mixture. The target is often collected with several co-eluting species at this stage. There are many orthogonal column chemistries available in SFC and through the proper selection of a well performing column separation system; the target can then be obtained in its pure form from the second dimension of preparative SFC.  Both SFE and SFC operate under oxygen free conditions and have dry downs using mild temperature conditions, which allows for the successful isolation of some less stable compounds. Several examples will be presented demonstrating that these processes can be used as a general workflow designed for the isolation of many different natural products.<br/>

SFE and preparative SFC with mass directed collection as beneficial tools in the workflow for natural products isolations from complex mixtures

253rd National Meeting (2017)

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