Synthesis of (-)-α-Kainic Acid

Significance

Kainic acid is used to reproduce neuronal cell death for the study of Alzheimer’s disease and epilepsy. Its supply from the natural source (the alga Digenea simplex) is intermittent and hence there is a spur for a good synthesis. There are now 19 total syntheses and five formal syntheses of (-)-Kainic acid but efficiency and scalability remain elusive. The present synthesis for the first time uses trans-4-hydroxy-l-proline (A) as the starting material. A noteworthy step is the nucleophilic substitution of a secondary tosylate by an alkenylcuprate (G to H) with retention of configuration.