A new toxic metabolite of Pithomyces chartarum related to the sporidesmins

Chemical Communications (London)
1968.0

Abstract

We have reported that Pithomyces chartarum produces several sulphur-containing metabolites other than sporidesmin (I). A new metabolite (named sporidesmin-E) was isolated by chromatography (silica gel) of the sporidesmin fraction with the solvent n-pentane-t-butyl alcohol (17 : 3), obtained as the etherate with m.p. 155-165", [α]306 + 2920"; [α],,, -44,0OOc (c 0.46, MeOH), m/e 505 and 507, and elemental analysis agreeing with the molecular formula C19H20ClN3O6S3. Sporidesmin-E formed a diacetate, gave sporidesmin-D on treatment with sodium borohydride and methyl iodide, was synthesized from sporidesmin (I) with excess sulphur and phosphorous pentasulphide in carbon disulphide (40% yield), and reacted with triphenylphosphine in ether to give the corresponding disulphide (50% yield), providing evidence for proposed structure (II). Dehydrogliotoxin (III) reacted with triphenylphosphine in tetrahydrofuran to give a product (IV) with analogous i.r., U.V. and n.m.r. spectra. The n.m.r. spectrum of sporidesmin-E suggested it was a mixture of isomers, likely due to different stable conformations of cyclic trisulphides. Toxicity tests showed sporidesmin-E was more cytotoxic to HeLa cells (end-point 0.1 mpg./ml) than sporidesmin (no activity below 1 mpg./ml), being the most cytotoxic mould metabolite described so far. The monosulphide (IV) at 65 pg./ml inhibited the growth of Bacillus subtilis. Stepwise desulphurisation of these natural products is of diagnostic and biological interest, with other examples under investigation.

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