Abstract:
Natural products represent a rich source of bioactive compounds, covering a large chemical space. Even if challenging, this diversity can be extended by applying chemical modifications. However, these studies generally require multigram amounts of isolated natural products and face frequent testing failures. To overcome this limitation, we propose a rapid and efficient approach that uses molecular networking (MN) to visualize the new chemical diversity generated by simple chemical modifications of natural extracts. Moreover, the strategy deployed enables the most appropriate reagents to be defined quickly upstream of a reaction on a pure compound, in order to maximize chemical diversity. This methodology was applied to the latex extract of Euphorbia dendroides to follow the reactivity toward a series of Brønsted and Lewis acids of three class of diterpene esters identified in this species: jatrophane, terracinolide, and phorbol. Through the molecular networking interpretation, with the aim to illustrate our approach, BF3·OEt2 was selected for chemical modification on isolated jatrophane esters. Three rearranged compounds (3-5) were obtained, showing that the most appropriate reagents can be selected by MN interpretation.
摘要:
天然产物代表了生物活性化合物的丰富来源,覆盖了一个巨大的化学空间。即使具有挑战性,这种多样性可以通过应用化学修饰来扩展。然而,这些研究通常需要大量的分离的天然产物,并面临频繁的测试失败。为了克服这个限制,我们提出了一种快速有效的方法,该方法使用分子网络(MN)可视化由天然提取物的简单化学修饰产生的新化学多样性。此外,所部署的策略能够在纯化合物的反应上游快速定义最合适的试剂,以最大限度地提高化学多样性。将此方法应用于一品红的乳胶提取物,以跟踪对该物种中鉴定出的三类二萜酯的一系列布朗斯特德和路易斯酸的反应性:jatrophane,terracinolide,和佛波尔。通过分子网络解释,为了说明我们的方法,选择BF3·OEt2对分离的麻风烷酯进行化学修饰。得到三个重排的化合物(3-5),表明通过MN解释可以选择最合适的试剂。