Sporidesmin

Sporidesmin.—As part of the general interest currently being shown in the steric course of biosynthetic transformations, the stereochemistry associated with entry of the hydroxy-group at C-3 of sporidesmin (129) has been investigated. Samples 

The results with the tritiated tryptophan samples further indicate that hydrox-ylation at the carbon which corresponds to C-3 of tryptophan occurs with loss of the pro-R hydrogen, i.e. hydroxylation with retention of configuration. This result was probably to be expected for it is a well-founded rule that biological hydroxylation occurs with retention of configuration, and this then is an additional example from the field of secondary metabolites. 

Cyclopiazonic Acid.—a-Cyclopiazonic acid (132) is formed in vivo from tryptophan via (130) and j8-cyclopiazonic acid (131). The stereochemistry of the final oxidative cyclization reaction has been explored using (3RS)-, (3R)-, and (3S)-[3- H]tryptophan (see above for application in a study of sporidesmin hydroxylation). Half the tritium was retained with the (3RS) sample, demonstrating that 

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The epidithioketopiperazine shown above is present in natural products, including the gliotoxins and sporidesmins. ... 

In the 1970s, Kishi published a series of landmark papers [36] describing the total syntheses of ( )-dehydrogliotoxin (1973) [36b], ( )-sporidesmin A (1973) [36c], ( )-gliotoxin (1976) [36d], and ( )-hyalodendrin (1976) [36e] in which he employed a new method for epidithiodiketopiperazine synthesis (Scheme 9.4). Cognizant of the harsh conditions required in all of the sulfur incorporation methods developed at the time, it was determined that thiolation would be performed in the early stages of the syntheses. A dithiol intermediate obtained in a similar fashion to Trown s epidithiodiketopiperazine was protected as a dithioacetal, and after elaboration of this core diketopiperazine structure, the dithioacetal was unraveled under mild conditions in the final steps to afford the target epidisulfides. 

Safe S, Taylor A, Sporidesmins. XIII. Ovine Ill-thrifr in Nova Scotia. III. Characterization of chetomin, a toxic metabolite of Chaetomium cochliodes and Chaetomium globosum, J Chem Soc Perkin Tmm 74 472—479, 1972. 

C-acylation with acid chloride has been used by Kishi in the synthesis of sporidesmin A (73JA6493). The carbanion from the appropriate pipera-zinedione (derived by treatment with butyl lithium) was reacted with the... 

Aromatic azapentalenes have not been found naturally, though an imidazo[4,5-d]imidazole derivative has been implicated in the prebiotic synthesis of purines130 74 (see also Section III,A,l,d). Saturated derivatives occur fairly widely the Senecio alkaloids contain the reduced pyrrolol l,2-a]pyrrole (pyrrolizidine) skeleton,487 and the alkaloid withasomnine is a derivative of pyrrolo[ l,2-6]pyrazole.374,488 The mitomycin antibiotics mentioned earlier in this review (Sections III,B,l,f and III,B,5) contain the pyrrolol l,2-a]indole ring,166,331 and the recently reported fungal metabolite sporidesmin is a saturated derivative of pyrrolo[2,3-6]indole.489... 

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). 

A related oxidative cyclization of a complex indolic intermediate constituted a key step in the total synthesis of sporidesmin-A [58],... 

Chlorometabolites are widely distributed in fungi, early examples of which chlorometabolites are the antifungal agent griseofulvin (1) and the toxic sporidesmins (e.g. 2). Chloramphenicol (3), chlortetracycline (4) and ascamycin (5) are examples of chlorinated antibiotics produced by bacteria. 

Some 13C n.m.r. data for sporidesmin and sporidesmin-D have been published,25 and evidence has been presented for there being a certain amount of strain in the sporidesmin molecule, imposed by the epidithio bridge. 

A mass spectrometric investigation176 proved that sporidesmin B (302) has the same carbon skeleton as sporidesmin, and differs only in the absence of a hydroxyl group attached to ring C. Key... 

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. 

In connection with the synthesis of naturally occurring 3a-hydroxypyrroloindole derivatives, e.g. brevianamide E and sporidesmin A, it is of interest to note that the photosensitized oxidation of Nb-methyltryptamine with singlet oxygen affords the 4a-hydroxyoxazinoindole (8a) and the 3a-hydroxypyrroloindole (8b) via the 3a-hydroperoxy compound (8c) (Scheme 2). 

Chaetocin70" (75a) and verticillin A70b (75b), metabolites of Chaetomium minutum and a species of Verticillium from Coltricia cinnamomea respectively, are closely related dimers (Scheme 29) with S2-bridged diketopiperazine systems reminiscent of gliotoxin, sporidesmin, and aranotin. 

Sporidesmins, the series of sulfur-containing physostigmine-like metabolites, were isolated from Sporidesmium bakeri A (57), B (58) and C (59), a fungus that causes facial eczema and liver damage in farm animals, e.g. New Zealand sheeps [108-110]. Later studies identified sporidesmins D (60) [111], E (61) [112], F (62) [111], G (63) [113,114], H (64) [115]) and J 65) [115] from P. chartarum. Protonated [M+H]+ and deprotonated [M-H] ions were observed in positive and negative ion ESI modes, respectively [116]. In a further paper, complexation of sporidesmin A, with metals, was used for its analysis [117]. 

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