ASYMMETRIC SYNTHESIS--STRUCTURE, STEREOCHEMISTRY AND NMR

合成N-取代11-氮杂青蒿素1的新路线， 以11-azaartemisinin，2为起始原料， 在 优化反应条件制备2 分离出一种意想不到的产物，并确定其结构为 一种环己酮衍生物Posner等人已经分离出环己酮 类似物在研究青蒿素的作用机制方面的作用 类似物，并报道它们表现出抗疟疾活性。 作为 我们与梅什尼克教授合作的一部分， 青蒿素衍生物的作用及其体内外研究 神经毒性，我们制备了[3 H]-双氢青蒿素。 梅什尼克教授 和同事发现蒿乙醚和双氢青蒿素引起急性 大脑特定区域的神经元坏死，尤其是 前庭核和红核。 SDS凝胶上的放射自显影图， [3 H]-双氢青蒿素处理的细胞，显示四个神经元 分子量为27、32、40和81 kDa的蛋白质与 双氢青蒿素 与这些蛋白质反应所需的剂量 是治疗剂量的五千倍

A new route for the synthesis of N-substituted 11-aza-artemisinins, 1, was developed with 11-azaartemisinin, 2, as the starting material. In the course of optimizing reaction conditions for the preparation of 2 an unexpected product was isolated and its structure determined to be a cyclohexanone derivative Posner et al. Had isolated cyclohexanone analogs in their studies of the mechanism of action of artemisinin analogs and reported that they exhibited antimalarial activity. As part of our collaboration with Professor Meshnick on the mechanism of action of artemisinin derivatives and their in vitro and in vivo neurotoxicity, we prepared [3H]-dihydroartemisinin. Professor Meshnick and associates found that arteether and dihydroartemisinin caused acute neuronal necrosis in specific areas of the brain, especially the vestibular nuclei and red nuclei. Autoradiograms on SDS gels run from [3H]-dihydroartemisinin treated cells, showed that four neuronal proteins of molecular weights 27, 32, 40 and 81 kDa had reacted with dihydroartemisinin. The doses required to react with these proteins were 5,000 times the therapeutic dose.