Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
Org Biomol Chem. 2019 Jan 31;17(5):1062-1066. doi: 10.1039/c8ob02761g.
We report an efficient and highly diastereoselective protocol for the rapid construction of 3-nitro substituted 4-chromanones by an intramolecular Michael-type cyclization of α-nitro aryl ketones bearing unsaturated ester units. A catalytic amount of KOtBu was found to be crucial for the high diastereoselective control of this transformation. With this protocol, a series of 3,3-disubstituted 3-nitro-4-chromanones were synthesized in good to excellent yields with high diastereoselectivities and showed moderate to good in vitro antitumor activities, representing promising antitumor hits for further drug discovery.
我们报告了一种高效、高度非对映选择性的方法，通过带有不饱和酯单元的α-硝基芳基酮的分子内迈克尔型环化反应，快速构建 3-硝基取代的 4-色满酮。研究发现，催化量的 KOtBu 对于这种转化的高非对映选择性控制至关重要。使用该方法，一系列 3,3-二取代的 3-硝基-4-色满酮以良好至优异的收率、高非对映选择性合成，并表现出中等至良好的体外抗肿瘤活性，为进一步的药物发现提供了有前途的抗肿瘤先导化合物。
