Skyrins

Erase et al., The Chemistry of Mycotoxins, Progress in the Chemistry of Organic Natural Products, Vol. 97, DOI 10.1007/978-3-7091-1312-7 12, 

An interesting crystalline 1 1 complex of (—)-luteoskyrin (787) and (+)-rugulosin A (786a) was reported by Jiang et al. in 2010 (578). This complex is formed by four hydrogen bonds between the two skyrins and the X-ray crystallographic structure is shown in Fig. 12.3. 

In its biosynthesis, skyrin (783) plays a central role (524). It is formed very early and is therefore the precursor for all skyrins they are formed from this parent compound by gradual condensation (536). Skyrin itself is formed from emodin (791), an anthraquinone, by phenolic oxidation, as demonstrated by Franck et al. (537). They reacted emodin (791) with potassium hexacyanoferrate (III) and produced skyrin (783) in a low yield. An even earlier precursor of skyrin is the diketonaphthol 790 (538). Franck et al. fed Penicillium islandicum cultures with 

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Other structurally related dianthrones occur in fungi. Penicilliopsin 8 was found in cultures of Penicilliopsis clavariaeformis and is easily oxidised by air in basic solution to give protohypericin 3 [30]. Skyrin 9 occurs in a variety of fungi such as Penicillium islandicum. It is closely related to 8 and can be reduced to this compound, as well as directly converted to protohypericin 3 [31, 32]. 

Parker JC, McPherson RK, Andrews KM, et al. Effects of skyrin, a receptor-selective glucagons antagonist, in rat and human hepatocytes. Diabetes 2000 49 2079-2086. 

Anthraquinones (from fungi). Over 40 monomeric A. derivatives are known from ascomycetes and imperfect fungi and there are several dimeric compounds (e.g., luteoskyrin, rugulosin, skyrin). Many A. have also been isolated from plants, lichens, basidio-mycetes, bacteria (streptomycetes), and insects ( an-thranoids). Some A. occur both in fungi and in lichens, e.g. chiysophanol, emodin, erythroglaucin, and physcion. 

C30H22O12, Mr 574.50, mp. 278 °C, [a]u -830° yellow, hepatotoxic mycotoxin from Penicillium islan-dicum. L. belongs to the bianthraquinones such as, e. g., rugulosin and skyrin. The biosynthesis proceeds on the polyketide pathway. On being fed daily with I mg toxin per 20 g animal, mice develop liver tumors within 6 months. The toxin accumulates in hepatic mitochondria. In the presence of Mg ions L. binds to double- and single-stranded DNA and inhibits the DNA-de-pendent RNA polymerases. L. has antimicrobial and cytotoxic properties and is active against protozoa. Chromosome breaks are induced in cell cultures. 

The kinetic resolution should be considerably enhanced if a chiral dicar-boxylic acid capable of ring formation to both 6-hydroxy groups of skyrin would be applied. We selected for this purpose 6,6 -dinitrodiphenic acid dichloride (32) which can easily be obtained in both enantiomeric forms. Reaction of (+)-(R)-binaphthol 31 with racemic 32 afforded the (+)-lactone 33, [a]p +213°, whereas the unreacted acid 34 showed a negative rotation (Scheme 7). Further investigations with the optically pure reagents indicated that (+)-(R)-31 forms only a lactone 33 with (+)-(R)-32 whereas (-)-( )-31 reacts only with (-)-( )-32. The same results were obtained with tetrachlorodiphenic acid dichloride. Similar observations have recently been published by Miyano and co-workers (ref. 20) for 1,1 -binaphthyl-2,2 -dicarboxylic dichloride. 

With these results in hand, we applied the method to ( + )-skyrin (30) and (-)-flavomannin A (14). After the usual work-up and chromatographic purification. 

The (S)-configuration of (+)-skyrin is further supported by a n.m.r. comparison of the esters obtained from the (R)- and (S)-binaphthols 31 and skyrin (30) with Mosher s acid (ref. 22). Because the chemical shift differences observed with the esters of (-)-binaphthol and (+)-skyrin were in good agreement, both compounds possess the same stereochemistry. 

Fig. 12.1 Skyrin-containing Penicillium species under the light microscope with 400-fold magnification...

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