Total synthesis and RXRα-mediated transcription studies of neriifolone B and related compounds.
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.
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Qirong
Q
Shen
Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, People's Republic of China.
Yi
Y
Dai
Institute for Biomedical Research, Xiamen University, Xiamen 361005, People's Republic of China.
Guanghui
G
Wang
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Fei
F
Yao
Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, People's Republic of China.
Yinghui
Y
Duan
Institute for Biomedical Research, Xiamen University, Xiamen 361005, People's Republic of China.
Haifeng
H
Chen
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: zhangweige2000@sina.com.
Weige
W
Zhang
Institute for Biomedical Research, Xiamen University, Xiamen 361005, People's Republic of China.
Xiaokun
X
Zhang
Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, People's Republic of China. Electronic address: tyaoxs@jnu.edu.cn.
Xinsheng
X
Yao
D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
C000593357:1,6-dihydroxy-5-methoxy-4',4'-dimethyl-4',5'-dihydropyran-6-one(2',3'-3,4)xanthone; D003374:Coumarins; D047490:Retinoid X Receptor alpha; D044004:Xanthones; C009689:xanthone
RXRα transcriptional inhibitory activity; Total synthesis; Xanthone