Toward a structure-activity relationship for apoptolidin: selective functionalization of the hydroxyl group array.
[reaction: see text] To investigate the structural basis for the exceptional selectivity and activity of apoptolidin (1), a strategy has been devised that allows for selective functionalization of seven of its eight hydroxyl groups based on progressive silyl protection, derivatization, and deprotection. The syntheses of these derivatives and their ability to inhibit F(0)F(1)-ATPase are reported.
Wender
Paul A
PA
Department of Chemistry, Stanford University, Stanford, California, 94305-5080, USA. wenderp@stanford.edu
Jankowski
Orion D
OD
Tabet
Elie A
EA
Seto
Haruo
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D018942:Macrolides; D024101:Mitochondrial Proteins; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D018942:Macrolides; D024101:Mitochondrial Proteins; D006180:Proton-Translocating ATPases; C114125:apoptolidin