Two potentially useful enantioselective routes to the kainoid amino acids have been developed based on two intramolecular pericyclic reactions using diethyl (L)-tartrate and (S)-O-benzylglycidol as chiral starting materials, respectively. Reaction of the δ,ε-unsaturated aldehyde 29c, prepared from diethyl (L)-tartrate, with Meldrum's acid 7 afforded a single adduct 31b diastereoselectively via spontaneous condensation and intramolecular hetero-Diels-Alder reaction. Hydrolysis of 31b gave the bicyclic lactone 32b bearing newly generated three contiguous chiral centers on the pyrrolidine ring whose structure was confirmed by converting it into kainic acid lactone 33, the known compound generated from kainic acid 1 by acid treatment. Reduction of 32b, followed by regioselective dehydration of the product 34 yielded the potential intermediate 35 of kainic acid 1. On the other hand, thermolysis of both alkyl-44a and aryl-44b-cis-olefinic aziridine esters, 44a and 44b, prepared from (S)-O-benzylglycidol 40, yielded the corresponding all-cis-trisubstituted pyrrolidines, 45a and 45b, diastereoselectively, via spontaneous generation of the 1,3-dipoles, 43a and 43b, and their intra-molecular [1,3]-dipolar cyclization. The former adduct 45a was converted into the potential intermediate 50 of kainic acid 1 via the α,β-unsaturated aldehyde 48. The latter adduct 45b was successfully transformed into acromelic acid A 4, toxic principle of the poisonous mushroom Clitocybe acromelalga, via highly stereoselective epimerization of the all-cis-diester 54.
