The synthesis of (-)-isodomoic acid C.
The neuroactive algal metabolite (-)-isodomoic acid C, a kainoid amino acid, has been synthesized for the first time. Asymmetric dearomatizing cyclization of an aromatic amide using a chiral lithium amide base generates a bicyclic enone containing a pyrrolidinone ring with the relative and absolute stereochemistry of the target. A further 15 synthetic steps, including conjugate cuprate addition to the enone of a side chain precursor, a Ru-promoted oxidation of the phenyl ring to the C2-carboxylic acid substituent, a regioselective Baeyer-Villiger reaction, and an E-selective Horner-Wadsworth-Emmons reaction, elaborate the cyclization product into the target molecule.
Clayden
Jonathan
J
School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK. j.p.clayden@manchester.ac.uk
Knowles
Faye E
FE
Baldwin
Ian R
IR
D017377:Diatoms / Q000737:chemistry; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D008387:Marine Toxins / Q000138:chemical synthesis*; D009498:Neurotoxins / Q000138:chemical synthesis; D000461:Rhodophyta / Q000737:chemistry
D008387:Marine Toxins; D009498:Neurotoxins; C012301:domoic acid; D007608:Kainic Acid