Bâtiment Hubert Curien 43, CPE Lyon-Campus LyonTech/la Doua, boulevard du 11 Novembre 1918, 69616, Villeurbanne Cedex, France.
Pharmaceuticals Division, Drug Discovery Department, Bayer AG, Müllerstrasse 178, 13353, Berlin, Germany.
Chemistry. 2020 Apr 1;26(19):4378-4388. doi: 10.1002/chem.201905461. Epub 2020 Mar 9.
A short synthetic approach with broad scope to access five- to seven-membered cyclic sulfoximines in only two to three steps from readily available thiophenols is reported. Thus, simple building blocks were converted to complex molecular structures by a sequence of S-alkylation and one-pot sulfoximine formation, followed by intramolecular cyclization. Seventeen structurally diverse cyclic sulfoximines were prepared in high overall yields. In vitro evaluation of these underrepresented, three-dimensional, cyclic sulfoximines with respect to properties relevant to medicinal chemistry did not reveal any intrinsic flaw for application in drug discovery.
本文报道了一种从易得的噻吩酚出发，仅通过两到三步反应即可合成五至七元环的环状亚砜亚胺的简洁合成方法，具有广泛的应用范围。因此，通过 S-烷基化和一锅法亚砜亚胺形成，再进行分子内环化的顺序，简单的构建块被转化为复杂的分子结构。十七种结构多样的环状亚砜亚胺以高总收率制备。对这些代表性不足的三维环状亚砜亚胺进行了与药物化学相关性质的体外评估，并未发现任何在药物发现中应用的固有缺陷。
