Kainoid amino acids

The red alga Digenea simplex has been used for the treatment of roundworm disease for centuries. Its active principle is kainic acid. The related domoic acid is a constituent of another red alga, Chondria armata, used for the same purpose. These compounds, known as kainoids, are potent neurotoxins and excitatory amino acids. Kainoids are important tools in neurophysiological research. Domoic acids are also produced by diatoms and were responsible for the shellfish poisonings known as amnesic shellfish poisonings that occurred in Canada in 1987. 

A more complex member of the kainoid amino acid class of natural products is isodomoic acid G. This structure lacks the C4 stereocenter but instead possesses an exocycUc tetrasubstituted alkene. The core structure was constructed in a single step by nickel-catalyzed cycUzation of 10 with the vinylzirconium alkylating reagent 11 in 74% yield (Scheme 8.12) [34]. Notably, the pyrrolidine five-membered ring, C2/C3 relative stereochemistry, and 1,3-diene motif were assembled in a completely stereoselective fashion in a single operation. Sequential deprotection and oxidation steps afforded isodomoic acid G. 

Parsons, A.F. (1996) Recent developments in kainoid amino acid chemistry. Tetrahedron, 52, 4149-4174. 

Pyroglntamic acid is a useful starting material for the synthesis of several naniral products, such as pyrtolidme alkaloids, kainoids, and other unnaniral amino acids. Interesting chemose-lecdve Michael additions of anions derived from pyroglntamates have been reported fsee Eqs. 4.54 and4.55. ... 

Moloney and co-workers (64) also made use of the morpholinone template in the synthesis of analogues of the kainoid group of amino acids. Treatment of the template under the conditions reported by Harwood furnished the expected adducts. In keeping with earlier observations, the reaction proceeded with complete facial selectivity generating the new C(3) stereogenic center with complete control. 

The kainoids are a well-known group of naturally occurring, nonpro-teinogenic amino acids of general structure 1 (Figure 1). They vary only in the nature of the C-4 substituent (which is always attached to the pyrrolidine ring via an sp2 center) and the absolute configuration at this position. All of the isolated derivatives exhibit S absolute stereochemistry at C-2 and a trans relative disposition of the C-2 and C-3 substituents. 

This chapter reviews recent developments in the synthesis of both naturally occurring and unnatural acromelic acids, important members of the kainoid class of neuroexcitatory nonproteinogenic amino acid. 

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