Laboratory of Food Chemistry, Wageningen University, 6708 WG Wageningen, The Netherlands.
Molecules. 2022 Mar 28;27(7):2203. doi: 10.3390/molecules27072203.
Phenol amides are bioactive compounds naturally present in many plants. This class of compounds is known for antioxidant, anti-inflammatory, and anticancer activities. To better understand the reactivity and structure-bioactivity relationships of phenol amides, a large set of structurally diverse pure compounds are needed, however purification from plants is inefficient and laborious. Existing syntheses require multiple steps, including protection of functional groups and are generally overly complicated and only suitable for specific combinations of hydroxycinnamic acid and amine. Thus, to facilitate further studies on these promising compounds, we aimed to develop a facile general synthetic route to obtain phenol amides with a wide structural diversity. The result is a protocol for straightforward one-pot synthesis of phenol amides at room temperature within 25 h using equimolar amounts of ,'-dicyclohexylcarbodiimide (DCC), amine, hydroxycinnamic acid, and sodium bicarbonate in aqueous acetone. Eight structurally diverse phenol amides were synthesized and fully chemically characterized. The facile synthetic route described in this work is suitable for a wide variety of biologically relevant phenol amides, consisting of different hydroxycinnamic acid subunits (coumaric acid, ferulic acid, and sinapic acid) and amine subunits (agmatine, anthranilic acid, putrescine, serotonin, tyramine, and tryptamine) with yields ranging between 14% and 24%.
酚酰胺是天然存在于许多植物中的生物活性化合物。这类化合物具有抗氧化、抗炎和抗癌活性。为了更好地了解酚酰胺的反应性和结构-生物活性关系，需要大量结构多样的纯化合物，但从植物中提取效率低且费力。现有的合成方法需要多个步骤，包括保护官能团，而且通常过于复杂，只适用于特定的羟基肉桂酸和胺的组合。因此，为了促进对这些有前途的化合物的进一步研究，我们旨在开发一种简便的通用合成路线，以获得具有广泛结构多样性的酚酰胺。其结果是一种在室温和 25 小时内使用等摩尔量的,'-二环己基碳化二亚胺 (DCC)、胺、羟基肉桂酸和碳酸氢钠在水性丙酮中一步合成酚酰胺的方案。合成了八种结构不同的酚酰胺，并进行了全面的化学表征。本工作中描述的简便合成路线适用于各种具有生物相关性的酚酰胺，包括不同的羟基肉桂酸亚基（咖啡酸、阿魏酸和芥子酸）和胺亚基（胍丁胺、邻氨基苯甲酸、腐胺、血清素、酪胺和色胺），产率在 14%至 24%之间。
