Meeting Organocatalysis with Drug Discovery: Asymmetric Synthesis of 3,3‿Spirooxindoles Fused with Tetrahydrothiopyrans as Novel p53-MDM2 Inhibitors

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• 作者：Shengzheng Wang ; Yan Jiang ; Shanchao Wu ; Guoqiang Dong ; Zhenyuan Miao ; Wannian Zhang ; Chunquan Sheng
• 刊名：Organic Letters
• 出版年：2016
• 出版时间：March 4, 2016
• 年：2016
• 卷：18
• 期：5
• 页码：1028-1031
• 全文大小：391K
• ISSN：1523-7052

文摘

An organocatalytic enantioselective Michael–Michael cascade reaction is developed for the synthesis of chiral spirotetrahydrothiopyrans. This highly functionalized scaffold was assembled in moderate to good yield (55–74%) and excellent diastereo- and enantioselectivities (>30:1 dr, ≥ 99% ee) with the creation of four consecutive stereogenic centers. The novel spiro-oxindole scaffold is validated as a new class of p53-MDM2 protein–protein interaction inhibitors with good antitumor activity.