AUTHOR=Huber Robin , Marcourt Laurence , Koval Alexey , Schnee Sylvain , Righi Davide , Michellod Emilie , Katanaev Vladimir L. , Wolfender Jean-Luc , Gindro Katia , Queiroz Emerson Ferreira TITLE=Chemoenzymatic Synthesis of Complex Phenylpropanoid Derivatives by the Botrytis cinerea Secretome and Evaluation of Their Wnt Inhibition Activity JOURNAL=Frontiers in Plant Science VOLUME=Volume 12 - 2021 YEAR=2022 URL=https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2021.805610 DOI=10.3389/fpls.2021.805610 ISSN=1664-462X ABSTRACT=

In this study, a series of complex phenylpropanoid derivatives were obtained by chemoenzymatic biotransformation of ferulic acid, caffeic acid, and a mixture of both acids using the enzymatic secretome of Botrytis cinerea. These substrates were incubated with fungal enzymes, and the reactions were monitored using state-of-the-art analytical methods. Under such conditions, a series of dimers, trimers, and tetramers were generated. The reactions were optimized and scaled up. The resulting mixtures were purified by high-resolution semi-preparative HPLC combined with dry load introduction. This approach generated a series of 23 phenylpropanoid derivatives, 11 of which are described here for the first time. These compounds are divided into 12 dimers, 9 trimers (including a completely new structural scaffold), and 2 tetramers. Elucidation of their structures was performed with classical spectroscopic methods such as NMR and HRESIMS analyses. The resulting compound series were analyzed for anti-Wnt activity in TNBC cells, with several derivatives demonstrating specific inhibition.