Massarenti Chiara, Bortolini Olga, Fantin Giancarlo, Cristofaro Dario, Ragno Daniele, Perrone Daniela, Marchesi Elena, Toniolo Gianluca, Massi Alessandro
Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara 17, I-44121 Ferrara, Italy.
Org Biomol Chem. 2017 Jun 7;15(22):4907-4920. doi: 10.1039/c7ob00774d.
The synthesis of a small collection of novel bile acid-bisphosphonate (BA-BP) conjugates as potential drug candidates is reported. The disclosed methodology relied on the installation of azide and thiol functionalities at the head and tail positions, respectively, of the BA scaffold and its subsequent decoration by orthogonal click reactions (copper-catalyzed azide-alkyne cycloaddition, thiol-ene or thiol-yne coupling) to introduce BP units and a fluorophore. Because of the troublesome isolation of the target conjugates by standard procedures, the methodology culminated with the functionalization of the BA scaffold with a light fluorous tag to rapidly and efficiently purify intermediates and final products by fluorous solid-phase extraction.
报道了一小批新型胆汁酸-双膦酸盐（BA-BP）缀合物作为潜在药物候选物的合成。所公开的方法依赖于分别在BA支架的头部和尾部位置引入叠氮化物和硫醇官能团，并随后通过正交点击反应（铜催化的叠氮化物-炔烃环加成、硫醇-烯或硫醇-炔偶联）进行修饰，以引入BP单元和荧光团。由于通过标准程序分离目标缀合物存在困难，该方法最终通过用轻质氟标签对BA支架进行功能化，以通过氟固相萃取快速有效地纯化中间体和最终产物。
