Some recent studies on the metabolites of fungi and lichens.

Various anthraquinonoid colouring matters grouped into (a) monomeric anthraquinones, (b) bianthraquinones and (c) modified bianthraquinones were isolated from Pen icillium islandicum, P. rugulosum, and other fungi. The unusual cagelike structures of hepatotoxic luteoskyrin, (—)rubroskyrin, (+ )rugulosin and their analogues are elucidated. The absolute stereochemical structures of these fungal colouring matters have been established on the basis of the x-ray crystallographical analysis of a bromination product of (+)tetrahydrorugulosin. The photoreaction of (—)luteoskyrin is discussed in elucidatirig the structure of the product, lumiluteoskyrin. In addition, (—)flavoskyrin, isolated from a strain of Penicillium islandicurn, has now been proved to be a modified bianthraquinone. An unusual dimerization reaction of the dihydroanthraquinones which were synthesized as model compounds for flavoskyrin is also discussed. (+)Rugulosin, skyrin, some fungal modified bixanthones and their related compounds have recently been found in certain lichens. The biogenetical correlation between the metabolites of fungi and lichens is discussed in the light of studies on the secondary metabolism of lichen mycobionts. iNTRODUCTION During the past several years, my co-workers and I have been much concerned with the problems of the anthraquinonoid colouring matters produced by Pencillium islandicum Sopp, P. rugulosum Thom and some other related fungi" 2• Until now more than twenty anthraquinoids have been isolated from these fungi, which are grouped into (a) monomeric anthraquinones, (b) bianthraquinones and (c) modified bianthraquinones14. The modified bianthraquinones, luteoskyrin, rubroskyrin and rugulosin, are not only remarkable with their peculiar chemical structures but also notable with respect to their biological activities as mycotoxins. The hepatotoxicity of luteoskyrin of Pencillium isiandicum which can cause liver cirrhosis and sometimes liver carcinoma in long term feeding experiments on mice and rats drew general attention, because the mould producing this compound has been found polluting some foodstuffs such as stored rice grains57. This happened in our country a few years before aflatoxin was reported as the factor of Turkey-X disease in England8' . Various toxicological and biochemical investigations have been carried out by some workers who found that (—)-luteoskyrin impairs the mitochondrial function and binds with DNA 109 S. SHIBATA at the site of pyrimidine bases in the presence of magnesium ion to inhibit the synthesis of nuclear RNA by the modification of DNA-dependent RNA-polymerase'°'3. The toxic effects of (+)rugulosin have also been studied extensively by Ueno and his collaborators'4 to show a similar but less toxic effect in comparison with (—)luteoskyrin, while (— )rugulosin has been found to have a weaker activity than the (+ )isomer. In the earlier stages of our investigation on these fungal metabolites, we proposed to represent the structures of (—)luteoskyrin, (—)rubroskyrin and (+ )rugulosin as formulated at (I), (II) and (I'), respectively; these were mainly based on their chemical reactions and i.r. spectral data' 16• (—)Luteoskyrin, C30H220,2, yellow crystals m.pt 281°(decomp.), [x]D —880°(dioxan). (—)Rubroskyrin, C3ØH22012, deep red crystals, m.pt 18 10 (decomp.). From Pencillium islandicum Sopp NRRL 1036, U and E strains. (+)Rugulosin, C30H220,0, yellow crystals, m.pt 290°(decomp.), [°]D+ 4920 (dioxan). From Pencillium rugulosum Thom, P. wortmanni Klöcker, P. tardum Thom, P. brunneum Udagawa, Endothia parasitica (Mull.) Anders. et Anders., E. fluens Shear et Stevens, Sepedonium ampullosporum Damon, P. variabile Sopp. Table 1. The jr. spectral absorption of (+)rugulosin, (—)luteoskyrin, (—)rubroskyrin and their acetates, cm1 Ketone C=O Non-chelated Chelated Acetate Alcoholic C==O Phenolic or OH