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The antitumor agent, asterriquinone (ARQ) is a known metabolite isolated from the mycelium of Aspergillus terreus IFO 61231). YAMAMOTO et al. reported that ARQ analogues having a 2, 5-dimethoxy-p-benzoquinone moiety (ARQ dimethyl ether: ARQDMe)2,3) and the 2, 5-diamino-p-benzoquinone moiety (diamino ARQ: ARQDA)4) did not show any Cytotoxicity. As reported in our previous communication5), a new metabolite, asterridinone, which has a furo [3, 2-b] furan moiety instead of the p-benzoquinone moiety of ARQ, did not show cytotoxic activity towards P388 mouse leukemia cells, while isoasterriquinone and neoasterriquinone which have the tert-or iso-pentenyl groups at the different position of the indole ring, were active as was ARQ. These results indicate that the 2, 5-dihydroxy-p-benzoquinone structure is more important for cytotoxic activity than the kind of prenyl groups and its position. In this study, to assess the contribution of the hydroxy group in the p-benzoquinone moiety to the cytotoxic activity of ARQ, we synthesized several ARQ derivatives, of which the one or two hydroxy group(s) were substituted with the acetyl, methoxy, and/or amino groups, and examined their cytotoxicity towards P388 cells. Materials and Methods Test CompoundsARQ and ARQ monoacetate (ARQAc) were isolated as the metabolic products from mycelium of Aspergillus terreus IFO 61235). ARQ diacetate (ARQDAc)6) and ARQDMe1) were prepared from ARQ by the usual method. ARQ monomethyl ether acetate (ARQMeAc)6) was prepared by methylation of ARQAc and ARQ monomethyl ether (ARQMe)6) was prepared from (v/v) aq NH3 (5ml) in EtOH (50ml) and allowed to stand overnight at room temperature. The resulting precipitate was collected, dissolved in diethyl ether and washed with 5% (w/v) aq NaHCO3. The organic layer was washed with water, dried over anhydrous Na2SO4, evaporated under reduced pressure and the residue was purified by column chromatography (SiO2, CH2Cl2). ARQA (23mg, 0.045mmol) was obtained in 78% yield.

Four new metabolites (1-4) were isolated from mycelium of Aspergillus terreus IFO 6123 producing asterriquinone (ARQ). The structures of 1 and 2 were shown to be 3,6-bis[1-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]-furo[3,2-b]furan- 2,5-dione (asterridinone) and 2,5-bis[1-(1,1-dimethyl-2-propenyl)-1H-indol-3- yl]-3-acetoxy-6-hydroxy-2,5-cyclohexadiene-1,4-dione (ARQ monoacetate), respectively, by the chemical and spectral data. Compounds 3 and 4 were identified with known asterriquinone isomers, 2-[1-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]-5-[2-(3-methyl-2-butenyl)- 1H-indol-3-yl]-3,6-dihydroxy-2,5-cyclohexadiene-1,4-dione (isoARQ) and 2,5-bis[2-(3-methyl-2-butenyl)-1H-indol-3-yl]-3,6-dihydroxy- 2,5-cyclohexadiene-1,4-dione (neoARQ), respectively.

O-Propargylic oximes that possess a proton at the α-position of the oxime group were effectively converted to the corresponding oxiranyl N-alkenylimines via a 5-endo-dig cyclization followed by the cleavage of the N-O bond.

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