National Natural Science Foundation of China [NSFC-30973614, NSFC-30873146] ; 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 alpha (RXR alpha). 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 RXR alpha-mediated transcription was evaluated. Two neriifolone B analogs, 17 and 11 '', were potent inhibitors of RXR alpha transcriptional activity. Preliminary structure-activity relationship studies are discussed briefly. (C) 2014 Published by Elsevier Ltd.