A total synthetic route to (-)a-kainic acid has been developed based on the Pauson-Khand reaction as a key reaction for the construction of the bicycle ring system.
The unique structure and novel biological activities (anthehninticl, insecticidal* and neuroexitatory activity) of kainic acid l, isolated from the marine algae Digenea Simpkx', had led to the development of several interesting synthetic atrategieti.
In this paper we would like to describe our continuing endeavors toward the total synthesis of optically active a-kainic acid baaed on the Pauaon-Khand reaction. Dealing with a synthetic scheme for cz-kainic acid, one should address the problems of not only building up necessary side chains but also controlling the stereochemistry at C2, C3 and C4 positions.
Retroaynthetic analysis (Scheme 1) of kainic acid euggeated that the ketone 2, which can be readily transformed into l, should, in principle, be derivable by the oxidative cleavage of the enolether 3. The enolether 3 would be obtained by trapping the enolate generated by the 1,4reduction of the enone 4. The moat important aspect in the scheme for controlling the atereochemiatry at C3 and C4 poaitiona lies in the fact that the reduction would proceed to form only the cia fused bicyclo13.3.0loctane ayatem due to the nature of the ring system. Furthermore, the trena stereochemistry between C2 and C3 positions would be realized during the Pauson-Khand reaction'.
Starting with an optically active vinylglycine derivative as, the ene-yne 10 waa prepared according to Scheme 2. The eater 6 waa reduced to 7 with LiBH, and the hydroxyl group waa Scheme 1 P, P': protacting groups