九里香抗生育活性物质——月橘烯碱的仿生合成研究

月橘烯碱是从芸香科植物九里香根中分出的双吲哚生物碱。药理实验结果表明它具有抗着床和抗早孕的活性。本文报道其仿生合成:吲哚经3位醛基化、与丙酮缩合成化合物Ⅱ;将氮原子保护后进行wittig反应,脱保护基得到β-异戊二烯吲哚(Ⅴ);经分子间Diels-Alder加成反应得消旋月橘烯碱(Ⅵ)。

Studies on the biomimetic synthesis of yuehchukene--a novel anti-implantation bis-indole alkaloid

Yuehchukene (Ⅵ), isolated from the roots of Murraya paniculata (named in China as Jiu-Li-Xiang), is a novel bisindole alkaloid with anti-implantation and thus anti-early pregnancy activities in rats. In this paper, the title compound (Ⅵ) was synthesized from indole through the following steps: formylation to give indole-3-carboxaldehyde(Ⅰ), then condensation with acetone, toluenesulfonylation of the nitrogen atom, Witting reaction, deprotection of the protecting group to give 3-isoprenylindole(Ⅴ) and intermolecular Diels-Alder cyclization successively. The overall yield was 7.5%. The spectral data (IR, ¹HNMR, UV and MS spectrum) and physical constants of the synthetic yuehchukene were identical with the natural product. The synthetic sample was administered to rats at 2 mg and 4 mg/kg. It was found to be 100% and 50% active for preventing implantation and terminating early pregnancy respectively. Meanwhile, two by-products, trimer and tetramer of Ⅴ, were obtained.