Clitidine

From recent literature it must be coneluded that mushrooms of the genera Inocybe and Clitocybe contain toxic components that are different from muscarine. The severe symptoms reported of an Israeli ehild poisoned with /. tristis therefore departed from what is known of musearine poisoning (Amitai et al., 1982). The toxic activities of C. acromelalga and C. amoenolens, two Clitocybe species containing clitidine and acromelic acid A, respectively, were studied in rats (Fukuwatari et al., 2001 Saviuc et al., 2003). 

N NMR spectroscopy studies of a natural toxic pyridine nucleoside, clitidine, in aqueous solution and X-ray crystallographic analysis in the solid state revealed that the imine 75 is predominant in the both states (98H(47)661). 

Clitidine 5 -mononucleotide (115) was isolated from the Japanese toadstool Clitocybe acromelalga. Its structure was determined by UV, FABMS, elemental analysis, and lH and 31p... 

NMR. The absolute configuration was established by phosphorylation of clitidine to give 115. Clitidine 5 -mononucleotide, like clitidine, was toxic to mice [332],... 

Clitidine was isolated among other nitrogen-containing principles from Clitocybe acromelalga, the toadstool long known in Japan as the cause of markedly increased hyperemia and hyperesthesia in fingers and toes. Pure... 

A new metabolite, 4-aminopyridine-2,3-dicarboxylic acid, was recently isolated from C. acromelalga in a yield of 0.000056% based on the weight of frozen fruiting bodies (41)5). A lethal effect of this compound on mice has not been observed however, bioactivity is still expected because of the similarity of its structure to the physiologicaUy active pyridine-2,3-dicarboxylic acid. The structure of this compound was deduced from H-NMR, C-NMR, and mass spectra, and the position of the substituents was assumed from comparison with clitidine, which contains a 4-aminopyridine-3-carboxylic acid moiety. The structural proposal was confirmed by synthesis from 2,3-dimethyl-4-nitropyridine 1-oxide (Scheme 91) when this compound was subjected to successive reduction and oxidation it yielded a product identical to the one occurring naturally. 

Conventional syntheses have been reported for 5-(bromoethynyl)-2 -deoxyuridine and for oxanosine and its S-thio analogue. Clitidine S -mono-phosphate 6, a toxic pyridine nucleotide, has been isolated from a Japanese toadstool, which had previously yielded the corresponding nucleoside. 3 -0-(P-D-Galactopyranosyl)-ara-C and 3 -0-[P-D-galactopyranosyl-(l->4)-C-(P-D-galactopyranosyl)]-ara-C have been isolated from the culture filtrate of Sporobolomyces singularis. 

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