Penicillium roqueforti alkaloids

These alkaloids possess most unusual structural features, namely the 1-methoxyindoline ring, the two nitrogen atoms directly attached to position 2 of this ring, giving a triaminomethane type of structure, and a dimethylallyl group at position 3 of the indole system. A related alkaloid, roquefortine, has been isolated (76E140) from Penicillium roqueforti, but does not possess a 1-methoxyl group. 

A Russian group has isolated360 roquefortine and 3,17-dihydroroquefortine from Penicillium roqueforti Thom F-141 the latter metabolite is presumably identical with Alkaloid Z (roquefortine D), isolated from the same microorganism by Abe s group.36d... 

In 1976 Scott et al. (186) isolated the neurotoxin roquefortine (144) from the fungus Penicillium roqueforti. Structure 144 was deduced on the basis of spectroscopic data and degradative products. The alkaloid appeared to be the same as roquefortine C, isolated by Ohmomo et al. in 1975 (187). The latter authors confirmed the structure by spectroscopic evidence (188) they also isolated roquefortine D. Reduction of roquefortine D with zinc in acetic acid yielded two dihydro derivatives. The properties of roquefortine C and of one of the isomers correlated very well. Thus, roquefortine D is dihydro-roquefortine C (189). The stereochemistry still remains to be solved. 

The amino acid tryptophan is a precursor of several fungal metabolites that affect the central nervous system. We have already met it as a constituent of the ergot alkaloids. Roquefortine (9.25) is a metabolite of Penicillium roqueforti and P. camemberti, which are found on some cheeses. Roquefortine is one of a series of mycotoxins that affect the central nervous system and induce tremors. The more complex penitrems are tremorogenic neurotoxins that are produced by the P. crustosum series. They are biosynthesized from a tryptophan and a triterpene unit. 

Scott, P. M., and Kennedy, B. P. C. (1976). Analysis of blue cheese for roquefortine and other alkaloids from Penicillium roqueforti. J. Agric. Food Chem. 24, 365-368. 

Mould Metabolites.—Alkaloid Z (now renamed roquefortine D), a minor metabolite of Penicillium roqueforti, proves to be simply dihydroroquefortine C (36), and may be prepared, together with a diastereoisomer, by the reduction of roquefortine C ( = roquefortine) by means of zinc and acetic acid. ... 

Ohmomo, S., Sato, T., Utagawa, T. and Abe, M. (1975) Isolation of festuclavine and three new indole alkaloids, roquefortine A, B and C from the cultures of Penicillium roqueforti. Agr. Biol. Chem., 39,1333—1334. 

Reshetilova, T.A. and Kozlovsky, A.G. (1985) The regulation of alkaloid biosynthesis by tryptophan and its analogs in Penicillium roqueforti. Mikrobiologiya (in Russian), 54, 699-703. 

Polonsky, J., Merrien, M.A., Prange, P., Pascard, C., and Moreau, S. (1980) Isolation and structure (X-ray analysis) of macfortine A, a new alkaloid from Penicillium roqueforti. J. Chem. Soc. Chem. Commun., 601-602. 

In 1976, two new nitrogen-containing metabolites were isolated from the mycelium of Penicillium roqueforti. The major metabolite was designated roquefortine and assigned structure 22 based on chemical and spectroscopic evidence. The minor metabolite was shown to be a stereoisomer of a known alkaloid, fumigaclavin A. Roquefortine possessed neurotoxic properties and caused convulsions in experimental animals. The LD50 to male mice was 15-10 mg/kg on i.p. injection (Scott et al., 1976). 

Neurotoxic mycotoxins of the indole alkaloid type from many mold fungi of the genus Penicillium. e.g., P. roqueforti. P cyclopium, P. commune, P crustosum, P. chrysogenum, P. griseofulvum. The R. occur in blue cheese and cotton seeds and have also been found in beer. The main alkaloid is R. C. R. can lead to abortions in animal experiments. Today, toxin-free strains are used for the production of cheese. R. C and R. D are formed from tryptophan, histidine (diketopipera-zine part) and mevalonic acid. R. A and R.B are alkaloids of the clavine type (see ergot alkaloids). The LD50 for mice (i.p.) is 15 mg R.C/kg. 

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