Marine Excitatory Amino Acids: Structure, Properties, Biosynthesis and Recent Approaches to Their Syntheses

Abstract

This review considers the results of recent studies on marine excitatory amino acids, including kainic acid, domoic acid, dysiherbaine, and neodysiherbaine A, known as potent agonists of one of subtypes of glutamate receptors, the so-called kainate receptors. Novel information, particularly concerning biosynthesis, environmental roles, biological action, and syntheses of these marine metabolites, obtained mainly in last 10-15 years, is summarized. The goal of the review was not only to discuss recently obtained data, but also to provide a brief introduction to the field of marine excitatory amino acid research.

Keywords: domoic acid; dysiherbaine; kainic acid; neodysiherbaine A.

Figure 1

Chemical structures of glutamic acid (1) and marine excitatory acids (2–5).

Figure 2

Some compounds closely related to kainic acid (6–8).

Scheme 1

Synthesis of kainic acid by Diels-Alder reaction.

Scheme 2

A shortcut scheme of synthesis of kainic acid via chirality transfer through the Ireland-Claisen rearrangement.

Scheme 3

Synthesis of kainic acid using the Ireland-Claisen rearrangement and palladium catalyzed formation of pyrrolidine ring.

Scheme 4

Short total synthesis of (–)-kainic acid.

Scheme 5

Synthesis of kainic acid using the Pd-catalyzed direct allylic amination.

Scheme 6

Syntheses of kainic and allo-kainic acids using SmI₂-induced cyclization.

Scheme 7

Biosynthesis of kainic acid.

Figure 3

Structures of synthetic derivatives of glutamic acid (46,47).

Figure 4

Dainic acids (56–59) and related metabolites (60,61) from C. armata.

Scheme 8

Synthesis of domoic acid.

Scheme 9

Biosynthesis of domoic acid.

Figure 5

Structures of dysiherbaine (74) and neodysiherbaine (75).

Scheme 10

Enanthioselective synthesis of (–)-dysiherbaine.

Scheme 11

Synthesis of neodysiherbaine A from methyl-α-D-mannopyranoside.