Huber Robin, Marcourt Laurence, Quiros-Guerrero Luis-Manuel, Luscher Alexandre, Schnee Sylvain, Michellod Emilie, Ducret Verena, Kohler Thilo, Perron Karl, Wolfender Jean-Luc, Gindro Katia, Ferreira Queiroz Emerson
School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland.
Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland.
Front Chem. 2022 May 31;10:912396. doi: 10.3389/fchem.2022.912396. eCollection 2022.
A series of complex stilbene dimers have been generated through biotransformation of resveratrol, pterostilbene, and the mixture of both using the enzymatic secretome of 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 (-δ-viniferin derivatives) against a methicillin-resistant strain of (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 -δ-viniferin derivatives against two strains were evaluated.
通过使用Pers.的酶分泌组对白藜芦醇、紫檀芪及其混合物进行生物转化，生成了一系列复杂的芪二聚体。该过程从非手性分子开始，最终生成具有多个手性碳的复杂分子。到目前为止，我们一直在以对映体混合物的形式研究这些化合物。在本研究中，我们分离了对映体以确定它们的绝对构型，并评估立体化学是否会影响它们的生物学性质。本研究选择了八种化合物，它们对应于生成的主要骨架（苍白醇、利奇醇、雷斯特醇和无环二聚体）以及对耐甲氧西林菌株（MRSA）最具活性的化合物（-δ-葡萄素衍生物）。为了分离这些对映体并确定它们的绝对构型，进行了手性HPLC-PDA分析。该分析在配备手性柱的高效液相色谱系统上完成。对于每种化合物，均获得了高纯度的相应对映体对。通过比较实验和计算的电子圆二色性（ECD）确定了每个对映体的绝对构型。评估了四种-δ-葡萄素衍生物对两种菌株的抗菌活性。
