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 the present work, a series of complex phenylpropanoids derivatives was obtained through chemoenzymatic biotransformation of ferulic acid, caffeic acid, and the mixture of both using the enzymatic secretome of Botrytis cinerea.  These substrates were incubated with the fungal enzymes and the reactions were monitored using state-of-the-art analytical methods. In such conditions, a series of dimers, trimers, and tetramers was 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. The elucidation of their structures was performed by classical spectroscopic methods such as NMR and HRESIMS analyses. The resulting compound series was analyzed for anti-Wnt activity in TNBC cells, with several derivatives demonstrating specific inhibition.