Biocatalytic approach to the chemoselective acylation of sesquiterpene lactones from chicory: a pathway to novel ester derivatives

In this study, we explore the use of the immobilized lipase Novozym 435 in the selective acylation of chicory sesquiterpene lactones (STLs) - lactucin (Lc), 11β,13-dihydrolactucin (DHLc), lactucopicrin (Lp), and 11β,13-dihydrolactucopicrin (DHLp) - using aliphatic vinyl esters as acyl donors. Despite the scarcity of these STLs due to their challenging extraction process and high cost, our results demonstrate the broad applicability and very high efficiency of this method. Furthermore, this methodology enables the selective esterification of the primary alcohol group without transesterifying the existing ester in the substrates. We also describe the enzyme-substrate binding modes in the acylation reactions with STLs, as well as the nature of their interactions with crucial amino acid residues at the active site, providing further insight into the potential of this approach. This study forms a foundation for the tailored functionalization of STLs, offering possibilities for the synthesis of STL derivatives with significant potential applications as pharmaceuticals or biocontrol agents.