Structural revision of thelephantin G by total synthesis and the inhibitory activity against TNF-alpha production.
This paper describes the total synthesis of thelephantin G, thus revising the proposed structure 1 to 2. The key steps involved a double Suzuki-Miyaura coupling and an esterification reaction. By a similar strategy, ganbajunins D and E (3 and 4) were also prepared. Compound 2 strongly inhibited TNF (tumor necrosis factor)-alpha production in rat basophilic leukemia (RBL-2H3) cells: IC(50) = 3.5 nM, while a mixture of 1 and its regioisomer 15 showed no such activity.
Ye
Yue Qi
YQ
RIKEN, Wako, Saitama 351-0198, Japan.
Koshino
Hiroyuki
H
Onose
Jun-ichi
J
Negishi
Chiemi
C
Yoshikawa
Kunie
K
Abe
Naoki
N
Takahashi
Shunya
S
D000818:Animals; D045744:Cell Line, Tumor; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D013237:Stereoisomerism; D013730:Terphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D013730:Terphenyl Compounds; D014409:Tumor Necrosis Factor-alpha