Sulfur-Containing Fungal Metabolites

While many sulfur-containing fungal secondary metabolites are known, they are found less frequently than in plants. There is a structural range from CH2S6, 1,2,3,4,5,6-hexathiapane, from Lentinus edodes, to C82Hii4N2oOi7S, a 13-unit peptide containing methionine from Saccharomyces cerevesiae,13 

The most famous fungal metabolites are, of course, the penicillins and cephalosporins. The association of sulfur and penicillin has a curious history. Penicillin was investigated chemically in 1932 by Harold Raistrick and his colleagues.14 The antibacterial activity could be extracted into ether from acid solution but on solvent evaporation the residue was without antibacterial activity. Clearly, penicillin was not a well-behaved natural product If only Raistrick had carried out a back-extraction from ether into dilute alkali, penicillin might have become available in the 1930s (and Raistrick would have become a Nobel Laureate). 

Also at Oxford, Abraham and Newton discovered the first cephalosporin, cephalosporin C, as a product of Acremonium chrysogenum (Cephalosporium acremonium).17 This new, sulfur-containing antibiotic was also a (5-lactam but the fused, sulfur-containing ring is a six-membered dihydrothiazine. 

The olivanic acids from S. olivaceus have side chains similar to that of thienamycin, with sulfur as either sulfide or sulfoxide 7 R, II or HOSO3, R2= SO CH=CH NH CO CH3 or S CH=CH NH CO CH3 or -S-CH2 CH2 NH CO CH3. The hydroxyethyl group (as in thienamycin) may be in a 

Dimeric structures are possible as exemplified by the leptosins, from a strain of Leptosphaeria (a fungus isolated from the marine alga Sargassum tortile). Some of these, e.g. leptosin A 11, may have up to 4 sulfur atoms across the diketopiperazine ring system.23 Various leptosins have antitumor and cytotoxic properties. 

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An allenyl sulfoxide containing triene underwent low-temperature IMDA reaction in situ to give a single product as a 60 40 mixture of diastereoiners at the asymmetric sulfur atom19. The intermediate was used as an intermediate in the synthesis of the fungal metabolite (+)-stcr-purene. 

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