Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin, squamostolide, and their inhibitory action with bovine heart mitochondrial complex I.
A convergent stereoselective synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin and squamostolide was accomplished via a Pd-catalyzed cross-coupling reaction. The inhibitory activity of these compounds was examined with bovine heart mitochondrial NADH-ubiquinone oxidoreductase. These compounds showed a remarkably weak inhibitory activity compared to ordinary acetogenins such as bullatacin. Our results indicate that to maintain potent inhibitory effect, the hydroxylated lactone cannot substitute for the hydroxylated mono- or bis-THF rings with a long alkyl chain that can be seen in ordinary acetogenins.
Makabe
Hidefumi
H
Sciences of Functional Foods, Graduate School of Agriculture, Shinshu University, 8304 Minami-minowa, Kamiina, Nagano 399-4598, Japan. makabeh@gipmc.shinshu-u.ac.jp
Kimura
Yuka
Y
Higuchi
Masaharu
M
Konno
Hiroyuki
H
Murai
Masatoshi
M
Miyoshi
Hideto
H
D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007536:Isomerism; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000480:Alkynes; D004791:Enzyme Inhibitors; D005663:Furans; D007783:Lactones; C475244:rollicosin; C506354:squamostolide; D042967:Electron Transport Complex I