New amino acids from clitocybe acromelalga. Possible intermediates in the biogenesis of mushroom toxins, acromelic acids

Tetrahedron
1993.0

Abstract

New amino acids, 3-(6-carboxy-2-oxo-3-pyridyl)-L-alanine, 3-(6-carboxy-2-oxo-4-pyridyl)-L-alanine and N-[2-(3-pyridyl)ethyl]-L-glutamic acid were isolated from the poisonous mushroom Clitocybe acromelalga and their structures were determined. Their occurrence in this fungus supports the previously proposed biogenesis of acromelic acids. The extraordinarily strong neuroexcitatory amino acids, acromelic acids A (1) and B (2), were recently found as toxic principles of the poisonous mushroom, Clitocybe acromelalga (Japanese name: Dokusasako). Because of their unique physiological activities, they attract very much interest pharmacologically and physiologically, and complete studies on these acids are expected. During further separation of the extracts of this mushroom to seek other toxins, we isolated several amino acids such as stizolobic acid, 3-(2-oxo-5-pyridyl)-L-alanine (3) and 3-(2-carboxy-4-pyrrolyl)-L-alanine (4), which implied a biogenesis of acromelic acids. We originally assumed the biogenesis of acromelic acids, which adopted the biogenesis of stizolobic acid from 3-(3,4-dihydroxyphenyl)-L-alanine (DOPA), to aid in the structural determination of acromelic acids. In the biogenesis, DOPA is cleaved in the catechol ring and subsequently recyclized to pyrone derivatives, stizolobic acid and a similar compound, which combine with glutamic acid to give acromelic acids (Scheme 2 and 3). Recently, the biosynthesis of the related neuroexcitant domoic acid by a marine diatom was reported. It was shown that domoic acid is assembled by condensation of geranyl pyrophosphate and glutamic acid. This is very similar to the biosynthetic pathway of acromelic acids proposed by us. In this report we would like to describe the isolation and structural determination of 3-(6-carboxy-2-oxo-3-pyridyl)-L-alanine (5), 3-(6-carboxy-2-oxo-4-pyridyl)-L-alanine (6) and N-[2-(3-pyridyl)ethyl]-L-glutamic acid (7). The occurrence of 7 in C. acromelalga appears to be biosynthetically derived from the compound originated in DOPA by condensation of glutamic acid. Isolation of 5, 6 and 7 will give further support to our biogenetic scheme.

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