Xanthones, chlorinated

Like depsides and depsidones, most chlorinated xanthones are found in lichens, and more than 50 such compounds were described in the first survey (/ ). The lichen... 

Pinselic acid (293) and related compounds, isolated from Penicillium amarum, have been synthesized from 3,6-dimethoxyphthalic anhydride and the lithium derivative (291) via the ketone (292). A number of the chlorinated xanthones found in lichens have been synthesized and their structures verified, using n.m.r. The roots of Hypericum androsaemum contain several xanthones, two of which [(294) and (295)] have an oxygenation pattern not previously known... 

The compounds were proposed to be dichloro C6-polychlorodibenzo-furans [46]. Similar observations from pulp mill samples were done by Kuehl et al. [47]. They suggested the structures of these compounds to be chlorinated xanthenes and xanthones. Buser et al. reported the occurrence of methyl-, polymethyl-, and alkyldibenzofurans in pulp mill sludge and sediments [48], Later, C5-PCBBs were detected as three dichloro and four trichloro congeners in pulp mill effluents, recipient sediment, and mussels incubated in recipient water [49]. Mass spectra of these congeners ruled out the structure of alkyl polychlorodibenzofurans and supported chlorinated alkyl bibenzyls instead, which was verified by model compound syntheses of the both structure types [50-52]. 

TCBTs are relatively persistent and non-flammable (and therefore useful in hydraulic oils). Pyrolysis in a closed system for two days in the presence of hydrogen peroxide at 300 °C produced as main components chlorinated benzo-phenones, fluorenes, fluorenones, xanthenes, and xanthones. Polychlorodiben-zofurans (PCDF) and polychlorodibenzo-p-dioxins (PCDD) were formed in much lower concentrations than from PCB product Pyralene T1 under identical conditions [84]. In pyrolysis at 450-700 °C with excess oxygen TCBTs produce more PCDFs and PCDDs. In parallel with the behavior of PCBs, PCDFs are formed in significantly higher amounts than PCDDs from PCBTs [86],... 

A second large group of polyketide metabolites that have been isolated from lichens are heptaketide xanthones. Their structures are mainly based on norli-chexanthone (7.54). An interesting feature of these compounds is the presence of chlorine in several of the metabolites. Lichens also produce some anthraquinone pigments, exemplified by physcion (7.6) from Xanthora species. 

Like the fungal and lichen xanthones, anthraquinones, which are also produced both by lichens and fungi, are derived from extended polyketides by cyclization. Several chlorinated compounds were described. 

Fitzpatrick L, Sala T, Sargent MV (1980) Further total syntheses of chlorine-containing lichen xanthones. J Chem Soc Perkin Trans 1 85-89... 

Xanthones are known in free-living fungi, and recent studies indicate that they are rather common in lichens too. Unlike the fungal xanthones, many lichen xanthones have one or more nuclear chlorine substituents. The fundamental structure of the known lichen xanthones could be derived directly by linear condensation of seven acetate and malonate units with one orsellinic acid-type cyclisation. The two rings are joined by a ketonic carbon and by an ether-oxygen arising from cyclodehydration. Xanthones include arthothelin, concretin,... 

Seven new lichen xanthones have been isolated and identified in the past decade, and these are listed in Table 1. Six of these new compounds (125 —130) vary only in the degree of O-methylation and ring chlorination like all the previously identified lichen xanthones. However erythrommone (131), isolated from Haematomma erythromma, provides the first example of an O-acetylated lichen xanthone. 

In addition to the synthesis of chlorinated lichen xanthones from suitably substituted mononuclear aromatic precursors, the elaboration of preformed xanthones through chlorination has also been reported 128, 138, 250). 

Fitzpatrick, L., T. Sala, and M. V. Sargent Further Total Synthesis of Chlorine Containing Lichen Xanthones. J. Chem. Soc. (London) Perkin Trans. I 1980, 85. 

Chemical Studies on Lichens. 21. Two Novel Chlorinated Lichen Xanthones. Ark. Kemi 31, 121 (1969). 

Steyn and Vleggaar (1974, 1975) characterized nine austocystins (42-50) from Aspergillus ustus (Bainier) Thom, and Church. The xanthone and bisdihydrofuran moieties of the austocystins are linearly fused and frequently contain either an isopentyl side chain or a chlorine atom. The cytotoxicity of the austocystins was determined in primary kidney epithelial cells of Cercopithecus aethiops pygerythrus austocystins A-D (42-45) are more toxic than sterigmatocystin in this system (Steyn et al., 1977). The most toxic compounds caused severe lesions in cells (nucleolar segregation), an indication of disturbed nucleic acid metabolism. 

Steyn and Vleggaar (1974, 1975) obtained nine new linear xanthones together with averufin (8) and versicolorin C (25) from corn cultures of A. ustus. The linear xanthones were called austocystins (42-50) and frequently contain a chlorine atom, e.g., austocystin A (42), or an isopentyl side chain, e.g., austocystin B (43). The substitution pattern of the austocystins was confirmed by the results of chemical modification, as well as NMR techniques, particularly acetylation shifts, benzene-induced solvent shifts, and nuclear Overhauser enhancement (NOE) effects. 

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