Six domoic acid related compounds from the red alga, Chondria armata, and domoic acid biosynthesis by the diatom, Pseudo-nitzschia multiseries

Domoic acid (DA, 1 ), a potent neurotoxin that causes amnesic shellfish poisoning, has been found in diatoms and red algae. While biosynthetic pathway towards DA from geranyl diphosphate and l -glutamate has been previously proposed, its late stage is still unclear. Here, six novel DA related compounds, 7′-methyl-isodomoic acid A ( 2 ) and B ( 3 ), N -geranyl- l -glutamic acid ( 4 ), 7′-hydroxymethyl-isodomoic acid A ( 5 ) and B ( 6 ), and N -geranyl-3( R )-hydroxy- l -glutamic acid ( 7 ), were isolated from the red alga, Chondria armata , and their structures were determined. The compounds 4 and 7 , linear compounds, are predictable as the precursors to form the DA pyrrolidine ring. The compounds 2 and 3 are thought as the cyclized products of 7 ; therefore, dehydration and electron transfer from the internal olefin of 7 is a possible mechanism for the pyrrolidine ring formation. One terminal methyl group of the side chain of 2 and 3 is predicted to be oxidized to hydroxymethyl ( 5 , 6 ), and then to carboxylic acids, forming isodomoic acids A and B. Finally, the terminal olefin of isodomoic acid A would be isomerized to form DA. In addition, [ 15 N, D]-labeled 4 was incorporated into DA using the diatom, Pseudo-nitzschia multiseries , demonstrating that 4 is the genuine precursor of DA.