Pithomyces chartarum Sporidesmins

Pioneering studies on hypervalent iodine-induced reactions toward total syntheses of several natural products had been reported from the 1970s to the early 1980s. That is, Kishi and co-workers accomplished the total synthesis of sporidesmin A (120), which is a toxic metabolite of Pithomyces chartarum, by PIDA-mediated cyclization of tryptamine derivative 121, but, the yield of tricyclic compound 122 was only 30% [85] (Scheme 1). 

Sporidesmin is a naturally occurring polycyclic disulfane that contains the piperazinedione ring shown in Table 6. The corresponding trisulfane has been termed sporidesmin E. It has been obtained by extraction of Pithomyces chartarum followed by LC on silica gel. From the same organism, sporidesmin G, the corresponding tetrasulfane, has been obtained. These compounds are also biologically active. 

Sporidesmin B, one of the minor toxic metabolites of Pithomyces chartarum, was obtained (Scheme 6) by reducing the intermediate (60a) to (60b) and then by a sequence of steps which parallel those used for sporidesmin A. 

Sporidesmins are toxic metabolites of Pithomyces chartarum, and the cause of serious hepatoxic disease in sheep, J. W. Ronaldson, A. Taylor, E. P. White and R. J. Abraham, J. Chem. Soc., 3172 (1963) S. Safe and A. Taylor, J. Chem. Soc. Perkin I, 472 (1972) and references cited therein. 

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