Cyclopiazonic acid from Penicillium cyclopium

A similar type of linkage between coenzyme and protein in which position 8a of the flavin is at the oxidation level of carbonyl was found in thiamine dehydrogenase (from soil bacterial 138) and in P-cyclo-piazonate oxidocyclase from Penicillium cyclopium 88, 155). In these cases, however, it is probable that N(l) of a histidine residue constitutes the bridge to the protein backbone. The oxidation level of position 8a was deduced from decay data similar to those mentioned above for the 8a-thiohemiacetals. Of particular interest is the fluorescence profile of the flavin peptide obtained by trypsin-chymotrypsin hydrolysis of p-cyclopiazonate oxidocyclase. Fluorescence quenching similar to that observed with SD-flavin (9) is observed, but in this case the pK attributed to protonation of the histidine imidazole is shifted from 4.7 to 5.4, and the maximal fluorescence obtained is only 20% of that of FMN 164). Upon performic acid oxidation of the peptide the emission intensity is... 

Cyclopiazonic Acid.—a-Cyclopiazonic acid (93) is formed in Penicillium cyclopium from tryptophan via (91) and jS-cyclopiazonic add (92) (Scheme 5). Further... 

Pyrrolizidines compounds have been produced in connection with syntheses of other types of natural products. For example, Gensler and Hu prepared the dioxopyrrolizidine ester (46) as an intermediate in the synthesis of ( + )-slaframine, an indolizidine alkaloid obtained from cultures of Rhizoctonia leguminicola. The pyrrolidone ester (47), prepared from l-glutamic acid [Eq. (14)], was optically active, but the cyclized product, formed in quantitative yield from 47, was completely racemized. The synthesis of 2-acetyl-1,3-dioxopyrrolizidine (48) was carried out by Kruger and Arndt to assist with their investigations on model compounds aimed toward the total synthesis of a-cyclopiazonic acid, the main toxic principle of Penicillium cyclopium The spectra of the product (48) obtained in 30% overall yield was typical of an intramolecularly H-bonded enolized )S-... 

The fungal metabolite cyclopiazonic acid 1 (40) has been shown to derive from tryptophan, mevalonic acid, and acetate. The corresponding bis-seco-derivative (39) also gave an incorporation when administered to Penicillium cyclopium Westling and is, therefore, probably an intermediate.28... 

Cyclopiazonic Acid.—Cyclopiazonic acid (115) is formed in Penicillium cyclopium from mevalonate, tryptophan, and an acetate-derived C4 unit [heavy bonding... 

In 1973, Abe and co-workers 193) isolated cyclopiazonic acid (130, a-CA), mp 245-246°C, cyclopiazonic acid imine (131), mp 277-278°C, and bissecode-hydrocyclopiazonic acid (132, p-CA), mp 168-169°C, from the combined extracts of mycelia and culture filtrates of Asp. versicolor. Cyclopiazonic acid was also isolated from Asp. flavus 194) and Asp. oryzae 195) by other groups. Penicillium cyclopium Westling 196) also produced the above metabolites as well as the intermediate, a-acetyl-7-(P-indolyl)methyltetramic acid (133), mp 164-165°C. Cyclopiazonic acid is known to cause acute toxicosis in ducklings and rats 197). 

Ability to synthesize ergot alkaloids was tested in 31 fungal strains belonging to the genera Aspergillus and Penicillium that were isolated from Uzbekistan soils treated with pesticides for a long time (Kozlovsky et al., 1990). It was shown, that one of the examined strains—strain P. verrucosum var. cyclopium can produce cyclopiazonic acid. 

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