Synthesis of riccardin C and its seven analogues. Part 1: The role of their phenolic hydroxy groups as LXRalpha agonists.
Riccardin C, a nuclear receptor LXRalpha selective agonist, is an 18-membered macrocyclic bisbibenzyl isolated from several liverworts. Synthesis of riccardin C and its seven O-methylated derivatives was accomplished. The synthetic sequence highlights an intramolecular Suzuki-Miyaura coupling in the formation of the 18-membered biaryl linkage present in riccardin C. The structure-activity relationship of these compounds suggests that all of the phenolic hydroxy groups present in riccardin C are essential for the activation of LXRalpha.
Hioki
Hideaki
H
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Shima
Naoki
N
Kawaguchi
Kota
K
Harada
Kenich
K
Kubo
Miwa
M
Esumi
Tomoyuki
T
Nishimaki-Mogami
Tomoko
T
Sawada
Jun-ichi
J
Hashimoto
Toshihiro
T
Asakawa
Yoshinori
Y
Fukuyama
Yoshiyasu
Y
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D000071518:Liver X Receptors; D008956:Models, Chemical; D015394:Molecular Structure; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors*; D019800:Phenol / Q000737:chemistry; D013053:Spectrophotometry / Q000379:methods; D013329:Structure-Activity Relationship
D004988:Ethers, Cyclic; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; C505660:riccardin C; D019800:Phenol