Bouton Jakob, Van Hecke Kristof, Rasooly Reuven, Van Calenbergh Serge
Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
XStruct, Department of Chemistry, Ghent University, Krijgslaan 281 S3, 9000 Ghent, Belgium.
Beilstein J Org Chem. 2018 Nov 12;14:2822-2828. doi: 10.3762/bjoc.14.260. eCollection 2018.
Interfering with bacterial cell-to-cell communication is a promising strategy to combat antimicrobial resistance. The natural product hamamelitannin and several of its analogues have been identified as quorum sensing inhibitors. In this paper the synthesis of pyrrolidine-based analogues of a more lead-like hamamelitannin analogue is reported. A convergent synthetic route based on a key ring-closing metathesis reaction was developed and delivered the pyrrolidine analogue in 17 steps in high yield. Chemoselective derivatization of the pyrrolidine nitrogen atom resulted in 6 more compounds. The synthesized compounds were evaluated in a biofilm model, but were all inactive.
干扰细菌细胞间通讯是对抗抗菌耐药性的一种有前景的策略。天然产物金缕梅鞣质及其几种类似物已被鉴定为群体感应抑制剂。本文报道了一种更具先导物样的金缕梅鞣质类似物的基于吡咯烷的类似物的合成。开发了一种基于关键关环复分解反应的汇聚合成路线，以17步高产率得到了吡咯烷类似物。吡咯烷氮原子的化学选择性衍生化又得到了6种化合物。在生物膜模型中对合成的化合物进行了评估，但它们均无活性。
