*4.3. Probable Origin in Sponges*

The cellular origin of **74** and **75** has remained a mystery for a long time, since excitatory acids are usually present in plants or microorganisms, but not in animals such as sponges. In 2008, using dysiherbaine antibodies, Japanese scientists from Kitasato University [77] have found dysiherbaine-to show immunoreactivity in spherical cells harbored in mesohyl of the sponge *Lendenfeldia chondrodes*. These spherical cells were identified as *Synechocystis* cyanobacteria by a combination of ribosomal RNA gene sequencing and cell morphology analysis. Therefore, these excitatory amino acids are probably formed in symbiotic cyanobacteria inhabiting some sponges.

**Scheme 11.** Synthesis of neodysiherbaine A from methyl-α-*D*-mannopyranoside.

## **5. Conclusions**

Excitatory amino acids, found in marine organisms a few dozen years ago, continue to attract increasing attention by their unusual properties. Some of them, such as domoic acid and its analogues, are potent excitotoxicants harmful for humans and different marine mammals and birds. These substances may cause significant damage to both natural ecosystems and aquaculture farms. Kainic acid and some similar compounds, being specific agonists of kainate receptors, are used in experimental pharmacology to model epilepsy and other neurodegenerative diseases in animals. Application of these compounds have become an important approach to understanding of the biological roles, classification and modes of action of synaptic receptors. Other excitatory amino acids isolated from some sponges exert even more potent action on neurons of animals and humans than kainic and domoic acids do. The promising pharmacological properties of marine excitatory amino acids were an incentive for developing numerous syntheses of these natural products and their analogs.

The most interesting results of very recent research concerns the biosynthesis of kainic acid and chemico-enzymatic procedure, providing a more efficient obtaining of this compound than chemical syntheses. Another important discovery is the decoding of biosynthesis processes leading to domoic acid and isolation of a number of new natural derivatives of this excitant, so-called dainic acids. In the recent decade, the chiral organic synthesis allowed obtaining of kainic acid by short and effective pathways using different synthetic strategies. New hypotheses have been proposed that explain the biological origin of dysiherbaine and neodysiherbaine A in sponges from symbiotic cyanobacteria and the biological significance of kainic acid in algae producing this excitatory amino acid for their defense against grazers.

**Author Contributions:** V.A.S. analyzed chemical data and schemes of syntheses of excitatory amino acids, and wrote chemical parts of the review. I.V.S. analyzed information concerning biological aspects, including properties and biological roles of compounds, and wrote other parts of the review. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding beside Governmental.

**Acknowledgments:** Authors thank Natalya Ivanchina (PIBOC, FEB RAS) for critical reading of the manuscript and useful comments.

**Conflicts of Interest:** The authors declare no conflict of interest.
