Fusidienol A:  A Novel Ras Farnesyl-Protein Transferase Inhibitor from Phoma sp.

Xanthones and Oxepino[2, 3‐b]chromones from Three Endophytic Fungi

“…These data, and in particular the additional oxygen atom shown in the mass spectrum in comparison to normal xanthones, suggested a ring-enlarged xanthone, namely an oxepinoA C H T U N G T R E N N U N G [2, 3-b]chromen-6-one system, as present in fusidienol A (8 a). [40,41] The assignment was further confirmed by 1 H-1 H COSY, HMQC, and HMBC correlations ( Figure 1) and definitely established by X-ray crystallographic analysis of a single crystal of 1 (Figure 2). Enone 7 (Scheme 1) was prepared by oxidation of the allylic hydroxy group at C2 of microsphaeropsone A (1) with manganese dioxide; furthermore, single crystals suitable for X-ray crystallographic analysis could also be obtained (Figure 3).…”

“…We now report on the isolation of bioactive metabolites from the cultures of these productive fungi. Three new oxepinoA C H T U N G T R E N N U N G [2,3-b]chromen-6-ones (a very rare class of ring-enlarged xanthones), namely, microsphaeropsones A-C (1-3); a known oxepinoA C H T U N G T R E N N U N G [2,3-b]chromen-6-one, fusidienol A (8 a); [40,41] the new 3,4-dihydrofusidienol A (8 b); the two known anthraquinones citreorosein (4) [42] and emodin (5); [42] the known palmarumycine C 11 (6) [43] (bipendensin); [44] two known aromatic xanthones 9 a and 9 b; [45,46] and two new aromatic xanthones, namely, microxanthone (9 c) and seimatoxanthone A (10) were isolated in addition to the common fungal metabolites ergosterol and 5a,8a-epidioxyergosterol (Scheme 1 and 2). [47,48] A semisynthetic dihydrooxepinoA C H T U N G T R E N N U N G [2,3-b]chromen-6-one 7 was prepared by oxidation of the allylic alcohol 1 with manganese dioxide.…”

“…To the best of our knowledge, this example is the first dihydrooxepinoA C H T U N G T R E N N U N G [2,3-b]chromen-6-one system to be found in nature. Fusidienol A (8 a) [40,41] has a corresponding but completely unsaturated system (Scheme 2). Interestingly, isomeric chromone-3-oxepines, isofusidienols, were recently isolated from the endophytic fungus Chalara sp.…”

“…This finding was further supported by 13 C NMR spectroscopic data (see the Experimental Section) and by comparison with the reported values for fusidienol A (8 a). [40,41] Thus, the structure of microsphaeropsone C (3) was established as (2Z,4E,5aZ)-methyl 7-hydroxy-9-methyl-…”

“…7177) was isolated from the shoots of the plant Zygophyllum fortanesii, a halotolerant succulent from Valle Gran Rey (Gomera, Spain). From the crude extract of the culture in ethyl acetate, chromatography on silica gel afforded the known fusidienol A (8 a) [40,41] and the known aromatic xanthone 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester (9 a) [45,46] (Scheme 2). The co-occurrence of the ring-extended and aromatic xanthones 8 a and 9 a in the same fungus indicates their biogenetic relationship.…”