New enantioselective approach to the total synthesis of (-)-α-kainic acid

The total synthesis of (-)-alpha-Kainic Acid 1 has been accomplished using ethyl N-Boc-pyroglutamate 2 as starting material. The isopropenyl appendage was achieved from the elimination of the dimethylcarbinol introduced at C-4 via an aldol condensation of the lactam enolate of 2 and acetone. The acetate group at C-3 of the kainic acid structure was introduced via diethyl malonate Michael addition reaction to the 2,3-didehydroprolinate 8. This Michael addition reaction proceeds with complete stereocontrol over the newly generated stereogenic centres. Inversion of the configuration at C-3 in 9 through double bond formation followed by hydrogenation, neutral decarboxylation and further epimerization of the C-2 stereogenic centre in 12, gave rise to the desired natural product. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.