A novel acyclic oligomycin A derivative formed via retro-aldol rearrangement of oligomycin A

作者：Lysenkova Lyudmila N; Turchin Konstantin F; Korolev Alexander M; Bykov Evgenyi E; Danilenko Valery N; Bekker Olga B; Trenin Alexey S; Elizarov Sergei M; Dezhenkova Lyubov G; Shtil Alexander A; Preobrazhenskaya Maria N^*

来源：Journal of Antibiotics, 2012, 65(8): 405-411.

DOI：10.1038/ja.2012.38

• acyclic derivative of oligomycin A
• apoptosis
• F0F1 ATP synthase
• oligomycin A
• retro-aldol degradation
• tumor cell lines

The antibiotic oligomycin A in the presence of K2CO3 and n-Bu4NHSO4 in chloroform in phase-transfer conditions afforded a novel derivative through the initial retro-aldol fragmentation of the 8,9 bond, followed by further transformation of the intermediate aldehyde. NMR, MS and quantum chemical calculations showed that the novel compound is the acyclic oligomycin A derivative, in which the 8,9 carbon bond is disrupted and two polyfunctional branches are connected with spiroketal moiety in positions C-23 and C-25. The tri-O-acetyl derivative of the novel derivative was prepared. The acyclic oligomycin A derivative retained the ability to induce apoptosis in tumor cells at low micromolar concentrations, whereas its antimicrobial potencies decreased substantially. The derivative virtually lost the inhibitory activity against F0F1 ATP synthase-containing proteoliposomes, strongly suggesting the existence of the target(s) beyond F0F1 ATP synthase that is important for the antitumor potency of oligomycin A. The Journal of Antibiotics (2012) 65, 405-411; doi:10.1038/ja.2012.38; published online 23 May 2012

• 出版日期2012-8