title: Total synthesis and structure-activity investigation of the marine natural product neopeltolide.
abstract: The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity.
authors: Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois 60208, USA.
authors: Daniel W
authors: DW
authors: Custar
authors: Thomas P
authors: TP
authors: Zabawa
authors: John
authors: J
authors: Hines
authors: Craig M
authors: CM
authors: Crews
authors: Karl A
authors: KA
authors: Scheidt
mesh_terms: D000438:Alcohols / Q000737:chemistry; D000818:Animals; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D006801:Humans; D020128:Inhibitory Concentration 50; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009792:Oceans and Seas; D010080:Oxazoles / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000438:Alcohols; D001688:Biological Products; D002264:Carboxylic Acids; D018942:Macrolides; D010080:Oxazoles; C519136:neopeltolide