Total synthesis and structure-activity investigation of the marine natural product neopeltolide.
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.
Custar
Daniel W
DW
Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois 60208, USA.
Zabawa
Thomas P
TP
Hines
John
J
Crews
Craig M
CM
Scheidt
Karl A
KA
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
D000438:Alcohols; D001688:Biological Products; D002264:Carboxylic Acids; D018942:Macrolides; D010080:Oxazoles; C519136:neopeltolide