Ruggieri Francesca, Hance Philippe, Gioia Bruna, Biela Alexandre, Roussel Pascal, Hilbert Jean-Louis, Willand Nicolas
Univ. Lille, Inserm, Institut Pasteur de Lille, U1177-Drugs and Molecules for Living Systems, F-59000 Lille, France.
UMRT 1158 BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, Univ. Picardie Jules-Verne, YNCREA, Univ. Artois, Univ. Littoral Côte d'Opale, ICV-Institut Charles Viollette, F-59000 Lille, France.
Pharmaceuticals (Basel). 2023 May 22;16(5):771. doi: 10.3390/ph16050771.
Sesquiterpene lactones (STLs) are a large group of terpenoids most commonly found in plants of the Asteraceae family, e.g., in chicory plants, displaying a wide range of interesting biological activities. However, further studies on the biological potential of chicory-derived STLs and analogues are challenging as only four of these molecules are commercially available (as analytical standards), and to date, there are no published or patented simple extraction-purification processes capable of large-scale STLs isolation. In this work, we describe a novel three-step large-scale extraction and purification method for the simultaneous purification of 11,13-dihydrolactucin (DHLc) and lactucin (Lc) starting from a chicory genotype rich in these STLs and the corresponding glucosyl and oxalyl conjugated forms. After a small-scale screening on 100 mg of freeze-dried chicory root powder, the best results were achieved with a 17 h water maceration at 30 °C. With these conditions, we managed to increase the content of DHLc and Lc, at the same time favoring the hydrolysis of their conjugated forms. On a larger scale, the extraction of 750 g of freeze-dried chicory root powder, followed by a liquid-liquid extraction step and a reversed-phase chromatography, allowed the recovery of 642.3 ± 76.3 mg of DHLc and 175.3 ± 32.9 mg of Lc. The two pure STLs were subsequently used in the context of semisynthesis to generate analogues for biological evaluation as antibacterial agents. In addition, other described chicory STLs that are not commercially available were also synthesized or extracted to serve as analytical standards for the study. In particular, lactucin-oxalate and 11,13-dihydrolactucin-oxalate were synthesized in two steps starting from Lc and DHLc, respectively. On the other hand, 11β,13-dihydrolactucin-glucoside was obtained after a MeOH/HO (70/30) extraction, followed by a liquid-liquid extraction step and a reversed-phase chromatography. Together, this work will help facilitate the evaluation of the biological potential of chicory-derived STLs and their semisynthetic analogues.
倍半萜内酯（STLs）是一大类萜类化合物，最常见于菊科植物中，例如菊苣植物，具有广泛有趣的生物活性。然而，对菊苣衍生的STLs及其类似物的生物潜力进行进一步研究具有挑战性，因为这些分子中只有四种可商购（作为分析标准品），而且迄今为止，尚无已发表或获专利的能够大规模分离STLs的简单提取-纯化方法。在这项工作中，我们描述了一种新颖的三步大规模提取和纯化方法，用于从富含这些STLs及其相应的葡萄糖基和草酰基共轭形式的菊苣基因型中同时纯化11,13-二氢莴苣素（DHLc）和莴苣素（Lc）。在对100毫克冻干菊苣根粉进行小规模筛选后，在30℃下水浸17小时获得了最佳结果。在这些条件下，我们设法提高了DHLc和Lc的含量，同时促进了它们共轭形式的水解。在更大规模上，对750克冻干菊苣根粉进行提取，然后进行液-液萃取步骤和反相色谱法，可回收642.3±76.3毫克的DHLc和175.3±32.9毫克的Lc。随后，这两种纯STLs被用于半合成，以生成作为抗菌剂进行生物评估的类似物。此外，还合成或提取了其他未商购的所述菊苣STLs，用作该研究的分析标准品。特别地，分别从Lc和DHLc开始，通过两步合成了莴苣素草酸盐和11,13-二氢莴苣素草酸盐。另一方面，通过甲醇/水（70/30）萃取，随后进行液-液萃取步骤和反相色谱法，获得了11β,13-二氢莴苣素葡萄糖苷。总之，这项工作将有助于促进对菊苣衍生的STLs及其半合成类似物的生物潜力的评估。
