title: Synthesis and biological evaluation of a beauveriolide analogue library.
abstract: Synthesis of beauveriolide III (1b), which is an inhibitor of lipid droplet accumulation in macrophages, was achieved by solid-phase assembly of linear depsipeptide using a 2-chlorotrityl linker followed by solution-phase cyclization. On the basis of this strategy, a combinatorial library of beauveriolide analogues was carried out by radio frequency-encoded combinatorial chemistry. After automated purification using preparative reversed-phase HPLC, the library was tested for inhibitory activity of CE synthesis in macrophages to determine structure-activity relationships of beauveriolides. Among them, we found that diphenyl derivative 7{9,1} is 10 times more potent than 1b.
authors.affiliation: Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nagai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Doi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sekiguchi
authors.forename: Ichiji
authors.initials: I
authors.lastname: Namatame
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002788:Cholesterol Esters / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D002788:Cholesterol Esters; D047630:Depsipeptides; D000960:Hypolipidemic Agents; C013833:beauverolides