Facile synthetic access to and biological evaluation of the macrocyclic core of apoptolidin.
Oxidative cleavage of the C-20/C-21 bond in apoptolidin (1) provides two fragments of similar complexity, facilitating a divide-and-diversify strategy for the determination of the structural basis for apoptolidin's biological activity, the remarkably selective induction of apoptosis in sensitive cell lines. The ability of compounds derived from this cleavage to inhibit mitochondrial F(0)F(1)-ATPase is reported. [structure: see text]
Wender
Paul A
PA
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA. wenderp@stanford.edu
Jankowski
Orion D
OD
Tabet
Elie A
EA
Seto
Haruo
H
D017209:Apoptosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D018942:Macrolides / Q000737:chemistry* / Q000494:pharmacology*; D000432:Methanol / Q000737:chemistry; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction
D004791:Enzyme Inhibitors; D018942:Macrolides; D025261:Mitochondrial Proton-Translocating ATPases; C114125:apoptolidin; D000432:Methanol