Synthesis of all possible isomers corresponding to the proposed structure of montanacin E, and their antitumor activity.
Total synthesis of 4 and its three diastereomers is described. The key steps involve stereoselective formation of the tetrahydrofuran ring by a cascade cyclization of hydroxy tosylate 7 and an intermolecular cross metathesis between a tetrahydrofuran 5 and a gamma-lactone 6. Spectroscopic data of 4 and biosynthetic hypothesis strongly suggest it to be montanacin E. Inhibitory activities of 4 and its isomers against six human solid tumor cell lines were also evaluated.
Takahashi
Shunya
S
RIKEN, Wako, Saitama 351-0198, Japan. shunyat@riken.jp
Takahashi
Ryotaro
R
Hongo
Yayoi
Y
Koshino
Hiroyuki
H
Yamaguchi
Kazunori
K
Miyagi
Taeko
T
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001156:Artemia / Q000187:drug effects; D045744:Cell Line, Tumor; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D007536:Isomerism
D000970:Antineoplastic Agents; D005663:Furans; C552380:montanacin E