Chiral Separation of Stilbene Dimers Generated by Biotransformation for Absolute Configuration Determination and Antibacterial Evaluation

Robin Huber; Laurence Marcourt; Luis-Manuel Quiros-Guerrero; Alexandre Luscher; Sylvain Schnee; Emilie Michellod; Verena Ducret; Thilo Kohler; Karl Perron; Jean-Luc Wolfender; Katia Gindro; Emerson Ferreira Queiroz

doi:10.3389/fchem.2022.912396

Chiral Separation of Stilbene Dimers Generated by Biotransformation for Absolute Configuration Determination and Antibacterial Evaluation

Front Chem. 2022 May 31:10:912396. doi: 10.3389/fchem.2022.912396. eCollection 2022.

Authors

Robin Huber^{1

2}, Laurence Marcourt^{1

2}, Luis-Manuel Quiros-Guerrero^{1

2}, Alexandre Luscher³, Sylvain Schnee⁴, Emilie Michellod⁴, Verena Ducret⁵, Thilo Kohler³, Karl Perron^{1

5}, Jean-Luc Wolfender^{1

2}, Katia Gindro⁴, Emerson Ferreira Queiroz^{1

2}

Affiliations

¹ School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland.
² Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland.
³ Departement of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
⁴ Mycology Group, Plant Protection Research Division, Agroscope, Nyon, Switzerland.
⁵ Microbiological Analysis Platform, Microbiology Unit, Department of Botany and Plant Biology, University of Geneva, Geneva, Switzerland.

Abstract

A series of complex stilbene dimers have been generated through biotransformation of resveratrol, pterostilbene, and the mixture of both using the enzymatic secretome of Botrytis cinerea Pers. The process starts with achiral molecules and results in the generation of complex molecules with multiple chiral carbons. So far, we have been studying these compounds in the form of enantiomeric mixtures. In the present study, we isolated the enantiomers to determine their absolute configuration and assess if the stereochemistry could impact their biological properties. Eight compounds were selected for this study, corresponding to the main scaffolds generated (pallidol, leachianol, restrytisol and acyclic dimers) and the most active compounds (trans-δ-viniferin derivatives) against a methicillin-resistant strain of Staphylococcus aureus (MRSA). To isolate these enantiomers and determine their absolute configuration, a chiral HPLC-PDA analysis was performed. The analysis was achieved on a high-performance liquid chromatography system equipped with a chiral column. For each compound, the corresponding enantiomeric pair was obtained with high purity. The absolute configuration of each enantiomer was determined by comparison of experimental and calculated electronic circular dichroism (ECD). The antibacterial activities of the four trans-δ-viniferin derivatives against two S. aureus strains were evaluated.

Keywords: Botrytis cinerea Pers.; ECD calculations; MRSA; Staphylococcus aureus; biotransformation; chiral-HPLC; enantiomers; stilbene dimers.