Innovative strategies for chemo-diversification of natural products and discovery of potential new leads

Chemical engineering of crude plant extracts and biotransformation of natural products (NPs) using enzymes could be an alternative way for obtaining bioactive compounds. The concept of these approaches is to start from extracts and abundant NPs to obtain active compounds using chemical and biological reactions. Given that 20% of marketed drugs contain halogen atoms, a methodology has been developed to allow controlled halogenation of compounds directly in plant extracts [1]. In addition, biotransformation chemical reactions of single NPs using enzymes secreted by a phytopathogenic fungus have been successfully used to obtain a wide variety of compounds [2]. A metabolite profiling based in the UHPLC-PDA-ELSD-HRMS analysis were used to monitor these different reactions and highlight the presence of the new generated compounds. In the majority of cases, it was possible to improve the chemical diversity of the original NPs leading to the acquisition of active compounds from inactive scaffolds. In order to isolate, characterize and study the biological activities of the generated compounds, the use of high-resolution preparative chromatographic methods was mandatory. At this level, significant improvements for the efficient targeted isolation of given NPs through dry load injection and chromatographic gradient transfer methods have been made [3]. The applications, possibilities and limitations of these latest technologies will be illustrated with recent investigations performed in our laboratory.

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• References

• 1 Righi D, Marcourt L, Koval A. et al. Chemo-diversification of plant extracts using a generic bromination reaction and monitoring by metabolite profiling. ACS Comb Sci 2019; 21: 171-182.
• 2 Gindro K, Schnee S, Righi D. et al. Generation of antifungal stilbenes using the enzymatic secretome of Botrytis cinerea . J Nat Prod 2017; 80: 887-898.
• 3 Queiroz EF, Alfattania A, Afzana A. et al. Utility of dry load injection for an efficient natural products isolation at the semi-preparative chromatographic scale. J Chromatogr A 2019; In press:.