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, C3OH22012, 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 Klocker, 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

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真菌和地衣代谢产物的一些新近研究

从 Pen icillium islandicum、P. rugulosum 和其他真菌中分离出各种蒽醌类色素，分为 (a) 单体蒽醌、(b) 联蒽醌和 (c) 改性联蒽醌。阐明了肝毒性 luteoskyrin、(-)rubroskyrin、(+)rugulosin 及其类似物的不寻常笼状结构。这些真菌着色物质的绝对立体化学结构是基于 (+) 四氢芝麻素的溴化产物的 X 射线晶体学分析建立的。在阐明产品 lumiluteoskyrin 的结构中讨论了 (-)luteoskyrin 的光反应。此外，从海岛青霉菌株中分离的 (-)flavoskyrin 现在已被证明是一种改良的联蒽醌。还讨论了作为 flavoskyrin 的模型化合物合成的二氢蒽醌的不寻常二聚反应。最近在某些地衣中发现了 (+) Rugulosin、skyrin、一些真菌修饰的联氧杂蒽酮及其相关化合物。根据对地衣分枝杆菌次生代谢的研究，讨论了真菌与地衣代谢产物之间的生物遗传相关性。简介 过去几年，我和我的同事一直非常关注由岛屿青霉 Sopp、P. rugulosum Thom 和其他一些相关真菌产生的蒽醌类色素的问题” 2• 到目前为止，已有 20 多种蒽醌类从这些真菌中分离出来，这些真菌被归类为 (a) 单体蒽醌，(b) 联蒽醌和 (c) 改性联蒽醌 14。修饰的联蒽醌类，luteoskyrin、rubroskyrin 和 rugulosin，不仅以其独特的化学结构而引人注目，而且在作为真菌毒素的生物活性方面也引人注目。Pencillium isiandicum 的 luteoskyrin 的肝毒性在小鼠和大鼠的长期喂养实验中会导致肝硬化，有时会导致肝癌，这引起了普遍关注，因为已经发现产生这种化合物的霉菌会污染一些食品，例如储存的米粒 57。这发生在我国几年前，黄曲霉毒素在英国被报道为土耳其-X 病的因素8'。一些工作者进行了各种毒理学和生化研究，发现(-)-luteoskyrin 损害线粒体功能，并在镁离子存在的情况下在嘧啶碱基位点与DNA 109 S. SHIBATA 结合，从而抑制核的合成。由DNA依赖性RNA聚合酶'°'3修饰的RNA。Ueno 及其合作者 4 还广泛研究了 (+) rugulosin 的毒性作用，与 (-) luteoskyrin 相比显示出类似但毒性较小的作用，而 (-) rugulosin 的活性低于(+) 异构体。在我们对这些真菌代谢物的研究的早期阶段，我们提议分别表示在 (I)、(II) 和 (I') 中配制的 (-) luteoskyrin、(-)rubroskyrin 和 (+)rugulosin 的结构; 这些主要基于它们的化学反应和红外光谱数据'16• (-)Luteoskyrin, C30H220,2, 黄色晶体 m.pt 281°(decomp.), [x]D —880°(dioxan)。(-)Rubroskyrin，C3OH22012，深红色晶体，m.pt 18 10（分解）。来自岛屿青霉菌 Sopp NRRL 1036、U 和 E 菌株。(+) Rugulosin，C30H220,0，黄色晶体，熔点 290°（分解），[°]D+ 4920（二恶烷）。来自 Pencillium rugulosum Thom、P. wortmanni Klocker、P. tardum Thom、P. brunneum Udagawa、Endothia parasitica (Mull.) Anders。et Anders.、E.fluens Shear et Stevens、Sepedonium ampullosporum Damon、P. variabile Sopp。表 1. jr. (+)rugulosin、(-)luteoskyrin、(-)rubroskyrin 及其醋酸盐的光谱吸收，cm1 酮 C=O 非螯合螯合醋酸醇 C==O 酚类或 OH C30H220,2，黄色晶体 m.pt 281°（分解），[x]D —880°（二恶烷）。(-)Rubroskyrin，C3OH22012，深红色晶体，m.pt 18 10（分解）。来自 Pencillium islandicum Sopp NRRL 1036、U 和 E 菌株。(+) Rugulosin，C30H220,0，黄色晶体，熔点 290°（分解），[°]D+ 4920（二恶烷）。来自 Pencillium rugulosum Thom、P. wortmanni Klocker、P. tardum Thom、P. brunneum Udagawa、Endothia parasitica (Mull.) Anders。et Anders.、E.fluens Shear et Stevens、Sepedonium ampullosporum Damon、P. variabile Sopp。表 1. jr. (+)rugulosin、(-)luteoskyrin、(-)rubroskyrin 及其醋酸盐的光谱吸收，cm1 酮 C=O 非螯合螯合醋酸醇 C==O 酚类或 OH C30H220,2，黄色晶体 m.pt 281°（分解），[x]D —880°（二恶烷）。(-)Rubroskyrin，C3OH22012，深红色晶体，熔点 18 10（分解）。来自岛屿青霉菌 Sopp NRRL 1036、U 和 E 菌株。(+) Rugulosin，C30H220,0，黄色晶体，熔点 290°（分解），[°]D+ 4920（二恶烷）。来自 Pencillium rugulosum Thom、P. wortmanni Klocker、P. tardum Thom、P. brunneum Udagawa、Endothia parasitica (Mull.) Anders。et Anders.、E.fluens Shear et Stevens、Sepedonium ampullosporum Damon、P. variabile Sopp。表 1. jr. (+)rugulosin、(-)luteoskyrin、(-)rubroskyrin 及其醋酸盐的光谱吸收，cm1 酮 C=O 非螯合螯合醋酸醇 C==O 酚类或 OH U 和 E 菌株。(+) Rugulosin，C30H220,0，黄色晶体，熔点 290°（分解），[°]D+ 4920（二恶烷）。来自 Pencillium rugulosum Thom、P. wortmanni Klocker、P. tardum Thom、P. brunneum Udagawa、Endothia parasitica (Mull.) Anders。et Anders.、E.fluens Shear et Stevens、Sepedonium ampullosporum Damon、P. variabile Sopp。表 1. jr. (+)rugulosin、(-)luteoskyrin、(-)rubroskyrin 及其醋酸盐的光谱吸收，cm1 酮 C=O 非螯合螯合醋酸醇 C==O 酚类或 OH U 和 E 菌株。(+) Rugulosin，C30H220,0，黄色晶体，熔点 290°（分解），[°]D+ 4920（二恶烷）。来自 Pencillium rugulosum Thom、P. wortmanni Klocker、P. tardum Thom、P. brunneum Udagawa、Endothia parasitica (Mull.) Anders。et Anders.、E.fluens Shear et Stevens、Sepedonium ampullosporum Damon、P. variabile Sopp。表 1. jr. (+)rugulosin、(-)luteoskyrin、(-)rubroskyrin 及其醋酸盐的光谱吸收，cm1 酮 C=O 非螯合螯合醋酸醇 C==O 酚类或 OH