1-甲氧基-2-乙氧甲基-3,8-二羟基蒽醌的合成

Synthesis of 3, 8-dihydroxy-2-ethoxymethyl-1-methoxyanthraquinone

茜草科(Rubiaceae)植物短刺虎刺(Damna-canthus Subspinosus Hand-Mazz)俗名“岩石羊”,民间用于治疗鼻咽癌。利国威等从该植物中分得短刺虎刺素(Subspinosin)

The structure of Subspinosin was revised as 2-ethoxymethyl-3-hydroxy-1-meth-oxyanthraquinone by the authors. Thus, 8-Hydroxysubspinosin was assumed to be 3, 8-dihydroxy-2-ethoxymethyl-1-methoxyanthraquinone. It had also been isolated from Damna-canthus Subspinosus Hand-Mazz (Rubiaceae) and named 8-hydroxydamnacanthol-ω-ethylether by Li et al. Therefore, synthesis of. the title compound was performed. Friedel-Craftsalkylation of 4-acetoxy-3-bromophthalide (8) with 2, 6-dimethoxytoluene in the presenceof stannic chloride, followed by deacetylation with Zn/HCOOH afforded phthalide (10).Prtotection of the hydroxy group in 10 with benzyl group, followed by reductive cleavagewith Zn/KOH and cyclization with TFAA gave the anthrone (13). After oxidation anddemethylation, 13 was converted to trihydroxyanthraquinone (15). The latter underwentselective acetylation and methylation to afford a mixture of 3, 8-diacetoxy-1-methoxy-2-methylanthraquinone (17a) and 1, 3-diacetoxy-8-methoxy-2-methylanthraquinone (17b),which could be seperated by silicagel chromatography. Bromination of 17 with NBS, thenethoxylation of the bromo compounds affored the title compound (4) and its isomer (5)respectively. After comparison, it was found that the melting point and the spectra of NMR,IR of the synthetic compound 4 were different from those of 8-hydroxysubspinosin. Thus thestructure of 8-hydroxysubspinosin should be reinvestigated. The spectrum of NMR was similarto that of 8-hydroxy damnacanthol-ω-ethyl ether, but the melting point was 20℃ lower thanthat reported. At present, it is hard to conclude for lack of authentic sample to compare. Compound 4 showed antitumor activity against leukemia P388 cell in vitro. The growthinhibitory rate were 85.7%, 58.7%, 42.9% at the concentration of 100, 10, 1μg/mL res-pectively.