Department of Organic Chemistry, Faculty of Bioscience Engineering. Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
J Org Chem. 2010 Apr 2;75(7):2274-80. doi: 10.1021/jo100024b.
3-Hydroxymollugin 2 and 3-methoxymollugin 3 are cytotoxic compounds isolated as minor compounds from Pentas longiflora and Rubia cordifolia. Syntheses of 3-hydroxymollugin 2 and 3-methoxymollugin 3 were developed starting from easily available 3-bromomollugin 6. Surprisingly, it was found that the reaction of 3-bromomollugin 6 with sodium methoxide in methanol resulted in the formation of 3-methoxymollugin 3 and the ring-contracted methyl isopropenylfuromollugin 7. A mechanism for this ring contraction is proposed on the basis of a pericyclic retro oxa-6pi ring-opening reaction. A second synthesis of 3-hydroxymollugin 2 was based on epoxidation of methyl 3-(3-methylbut-2-enyl)-1,4-naphthoquinone-2-carboxylate 17 and subsequent reduction of the quinone moiety, ring transformation, and DDQ oxidation. The latter oxidation process results in 3-hydroxymollugin 2 along with the rearranged furomollugin 4, which is a ring-contracted analogue of the natural product mollugin 1.
3-羟基毛蕊异黄酮苷元 2 和 3-甲氧基毛蕊异黄酮苷元 3 是从小叶黑柴胡和茜草中分离得到的具有细胞毒性的化合物。从易得的 3-溴毛蕊异黄酮苷元 6 出发，开发了 3-羟基毛蕊异黄酮苷元 2 和 3-甲氧基毛蕊异黄酮苷元 3 的合成方法。令人惊讶的是，发现 3-溴毛蕊异黄酮苷元 6 与甲醇中的甲醇钠反应生成 3-甲氧基毛蕊异黄酮苷元 3 和环缩合的甲基异丙烯基呋喃毛蕊异黄酮苷元 7。基于周环反应的反-Oxa-6pi 开环反应，提出了这种环缩合的机制。3-羟基毛蕊异黄酮苷元 2 的第二个合成方法基于甲基 3-(3-甲基-2-丁烯基)-1,4-萘醌-2-羧酸酯 17 的环氧化，随后醌部分的还原、环转化和 DDQ 氧化。后一氧化过程导致 3-羟基毛蕊异黄酮苷元 2 与重排的呋喃毛蕊异黄酮苷元 4 一起生成，后者是天然产物毛蕊异黄酮苷元 1 的环缩合类似物。
