Microbiology Unit, Department of Botany and Plant Biology , University of Geneva , 30 quai Ernest-Ansermet , 1211 Geneva 4, Switzerland.
School of Biomedicine , Far Eastern Federal University , 8 Sukhanova St. , 690090 Vladivostok , Russia.
ACS Comb Sci. 2019 Mar 11;21(3):171-182. doi: 10.1021/acscombsci.8b00132. Epub 2019 Jan 17.
A generic procedure for direct bromination of polyphenol in crude plant extracts was developed to generate multiple "unnatural" halogenated natural products for further bioassay evaluation. To better control the halogenation procedure, the bromination was optimized with a flavonoid standard, and the reactions were monitored by high-performance liquid chromatography photometric diode array coupled to the evaporative light scattering detection (ELSD). ELSD detection was successfully used for a relative yield estimation of the compounds obtained. From the halogenation of hesperitin (11), five brominated compounds were obtained. After optimization, the reaction was successfully applied to the methanolic extract of Citrus sinensis peels, a typical waste biomass and also to the methanolic extract of the medicinal plant Curcuma longa. In both cases, the methanolic extracts were profiled by NMR for a rapid estimation of the polyphenol versus primary metabolite content. An enriched secondary metabolites extract was obtained using vacuum liquid chromatography and submitted to bromination. Metabolite profiling performed by ultrahigh purity liquid chromatography time-of-flight high-resolution mass spectrometry revealed the presence of various halogenated products. To isolate these compounds, the reactions were scaled up, and six halogenated analogues were isolated and fully characterized by NMR and high-resolution electrospray ionization mass spectrometry analyses. The antibacterial properties of these compounds were evaluated using in vitro bioassays against multiresistant strains of Staphylococcus aureus and Pseudomonas aeruginosa. Some of the halogenated derivatives obtained presented moderate antibacterial properties.
开发了一种通用的多酚粗提物直接溴化方法，以生成多种“非天然”卤化天然产物，用于进一步的生物测定评估。为了更好地控制卤化过程，使用黄酮类标准品对溴化进行了优化，并通过高效液相色谱-光电二极管阵列与蒸发光散射检测（ELSD）联用对反应进行了监测。ELSD 检测成功地用于获得的化合物相对产率的估计。从橙皮素（11）的溴化反应中，得到了五种溴化化合物。经过优化，该反应成功地应用于柑橘皮的甲醇提取物，这是一种典型的废生物质，也应用于药用植物姜黄的甲醇提取物。在这两种情况下，均通过 NMR 对甲醇提取物进行了快速估计多酚与初级代谢物含量的图谱分析。使用真空液相色谱法对富含次级代谢物的提取物进行了浓缩，并进行了溴化处理。通过超高效纯液相色谱-飞行时间高分辨率质谱法进行的代谢产物图谱分析揭示了存在各种卤化产物。为了分离这些化合物，将反应放大，并分离出六种卤化类似物，并通过 NMR 和高分辨率电喷雾电离质谱分析对其进行了全面表征。使用体外生物测定法评估了这些化合物对耐多药金黄色葡萄球菌和铜绿假单胞菌的抗菌性能。获得的一些卤化衍生物表现出中等的抗菌性能。
