Shen Qirong, Dai Yi, Wang Guanghui, Yao Fei, Duan Yinghui, Chen Haifeng, Zhang Weige, Zhang Xiaokun, Yao Xinsheng
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, People's Republic of China.
Bioorg Med Chem. 2014 May 1;22(9):2671-7. doi: 10.1016/j.bmc.2014.03.024. Epub 2014 Mar 24.
Neriifolone B (1), a natural product containing a novel 4',4'-dimethyl-4',5'-dihydropyran-6-one[2',3':3,4]xanthone skeleton, was found to be a potent inhibitor of transcription mediated by retinoid X receptor α (RXRα). The first total synthesis of neriifolone B (1) was achieved in 14 steps with an overall yield of 7.1%. A Claisen rearrangement was employed as the key step in the sequence. The activity of six natural xanthones and eight compounds related to neriifolone B (1) against RXRα-mediated transcription was evaluated. Two neriifolone B analogs, 17 and 11″, were potent inhibitors of RXRα transcriptional activity. Preliminary structure-activity relationship studies are discussed briefly.
Neriifolone B（1）是一种含有新型4',4'-二甲基-4',5'-二氢吡喃并[2',3':3,4]氧杂蒽骨架的天然产物，被发现是维甲酸X受体α（RXRα）介导的转录的有效抑制剂。Neriifolone B（1）的首次全合成以14步完成，总产率为7.1%。克莱森重排被用作该序列中的关键步骤。评估了六种天然氧杂蒽和八种与neriifolone B（1）相关的化合物对RXRα介导的转录的活性。两种neriifolone B类似物，17和11″，是RXRα转录活性的有效抑制剂。简要讨论了初步的构效关系研究。
