ABSTRACT
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.
Subject(s)
Kainic Acid/analogs & derivatives , Kainic Acid/chemical synthesis , Marine Toxins/chemical synthesis , Diatoms/chemistry , Neurotoxins/chemical synthesis , Rhodophyta/chemistryABSTRACT
Treatment of N-benzyl benzamides with a strong base (LDA or t-BuLi) followed by irradiation with a 500 W tungsten lamp provides, according to the substitution pattern of the starting amides, either norcaradienes or cycloheptadienones by overall insertion of the N-benzyl group into the benzamide's aromatic ring system. Chiral benzamides undergo the ring expansion with high (sometimes complete) stereospecificity. The reaction appears to occur via a series of pericyclic reactions (photochemical or thermal sigmatropic rearrangements and thermal electrocyclic reactions) following an initial dearomatizing cyclization.
