Synthesis and assignment of the absolute configuration of indenotryptoline bisindole alkaloid BE-54017.
Synthesis of the indenotryptoline bisindole alkaloid, BE-54017, was accomplished using osmium-promoted cis-dihydroxylation of maleimide as a key step. After optical resolution, the absolute configuration of this molecule was determined by comparing its optical rotation and HPLC profile to those obtained for BE-54017 derived from enantiopure cladoniamide A, whose stereochemistry has been reported previously. BE-54017 with the correct absolute stereochemistry induced apoptosis of epidermal growth factor (EGF)-stimulated EGF receptor overexpressing A431 cells and inhibited vacuolar-type H(+)-ATPase (V-ATPase).
Institute of Microbial Chemistry, Tokyo, 3-14-23 Kamiosaki, Tokyo 141-0021, Japan.
Tomoyuki
T
Kimura
Shuhei
S
Kanagaki
Yusuke
Y
Matsui
Masaya
M
Imoto
Takumi
T
Watanabe
Masakatsu
M
Shibasaki
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008301:Maleimides / Q000737:chemistry; D015394:Molecular Structure; D009992:Osmium / Q000737:chemistry; D013237:Stereoisomerism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; C579047:BE-54017; D026121:Indole Alkaloids; D008301:Maleimides; C043592:maleimide; D009992:Osmium; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D025262:Vacuolar Proton-Translocating ATPases