A Supercritical Fluid Based Approach to Sample Work-up, Analysis and Purification in Natural Product Research

Natural product research is a multifaceted research area that often starts with identification and isolation of bioactive compounds in complex extracts. Compared to synthetic compounds, natural products are often sterically more complex and have more chiral centers. Recent technological advances in separation science, including both instrumentation and column chemistries, have significantly improved the methodology for isolating bioactive compounds for downstream bioassay and pharmacological studies. Among which, supercritical fluid technologies, including both supercritical fluid chromatography (SFC) and supercritical fluid extraction (SFE), have experienced an unprecedented acceptance in the scientific community.

In this presentation, we will illustrate a supercritical fluid technology based workflow solution for the extraction, analysis and purification of bioactive compounds in natural products. SFE has long been used in natural product extraction. We will, however, focus on the tunability of the SFE process induced by the addition of polar co-solvents. With carefully selected experimental conditions, SFE can offer an additional dimension of separation to simplify ensuing chromatographic analysis and improve the sample loadability in chromatographic purification. For SFC applications, we will use several challenging sets of enantiomers and diastereomers from natural product extracts to demonstrate the superior separation power of SFC in chirality analysis. We will also demonstrate the orthogonality between SFC and reversed phase LC for the analysis and purification of some relatively polar constituents in a plant extract. Finally, we will present an example of large scale SFE-SFC process for isolating a naturally occurring bioactive compound under preclinical development.