Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University , Kaifeng, Henan 475004, P.R. China.
Division of Chemistry and Biological Chemistry, Nanyang Technological University , 21 Nanyang Link, 637371 Singapore.
J Org Chem. 2016 Oct 21;81(20):9620-9629. doi: 10.1021/acs.joc.6b01637. Epub 2016 Sep 30.
This work reports the first application of diarylthiazolidin-2,4-diones as nucleophiles in asymmetric catalysis. By utilizing chiral amino acid-based (thio)urea-tertiary amines as the catalysts, we successively established asymmetric conjugate addition to nitroolefins and sulfenylation to N-(sulfanyl)-succinimides of diarylthiazolidin-2,4-diones. Two series of biologically important 5-aryl-5-substituted thiazolidin-2,4-diones were obtained with high enantio- and diastereoselectivities (up to >99% ee and >19:1 dr). The enantioenriched adducts were found to show satisfactory anticancer activities against three different cancer cell lines using the MTT assay. All of these successes depended on the development of a general and expedient synthetic strategy to provide diverse 5H-thiazolidin-2,4-diones.
本工作报道了二芳基噻唑烷-2,4-二酮作为亲核试剂在不对称催化中的首次应用。通过利用基于手性氨基酸的(硫代)脲-叔胺作为催化剂,我们成功地建立了二芳基噻唑烷-2,4-二酮的不对称共轭加成到硝基烯烃和亚磺酰化到 N-(亚磺酰基)琥珀酰亚胺的反应。通过使用 MTT 测定法,两种具有重要生物活性的 5-芳基-5-取代噻唑烷-2,4-二酮以高对映选择性和非对映选择性(高达>99%ee 和>19:1dr)获得。对映体富集的加合物显示出令人满意的抗三种不同癌细胞系的抗癌活性。所有这些成功都依赖于开发一种通用且简便的合成策略,以提供多种 5H-噻唑烷-2,4-二酮。