ASYMMETRIC SYNTHESIS--STRUCTURE, STEREOCHEMISTRY AND NMR

在早期的工作中，我们开发了一种制备14-[2H]-芳香醚的方法，并 现在已经使用该反应序列制备了14-[~3H]-乙醚。 用~3H标记的芳香醚研究其作用机理。 这组抗疟疾药物。感染和未感染的红血 细胞用标记的蒿甲醚、双氢青蒿素和第三个 也包含相同内过氧基团的药物。同样的六个 在受感染的细胞中发现有反应的蛋白质，而没有 未受感染的红细胞中的蛋白质也不与这些化合物反应。 以[~3H]-脱氧乙醚为对照。这些发现使之成为可能 鉴定、纯化和研究活性物质的结构和功能 蛋白质。 伯醇在碳-碳双环上的非对映界面加成 三苯基膦催化脱水二氢青蒿素的成键 氢溴酸被用来制备一系列的11-溴化氢 表氢青蒿素衍生物。这些补充使我们能够准备 以前不为人知的表土植物醚类。11-二氢呋喃的抗疟疾活性 检查了EPI-双氢青蒿素，发现其活性是 天然构型为C-11的异构体。关于小反应的研究 产品作为所使用的酒精当量数量的函数， 提供了关于反应机理的宝贵信息 极化c-前线分子反应的立体化学 轨道理论。 硫化白僵菌的区域和立体选择性研究 1，4-二取代苯的介导羟化反应表明 烷基侧链的β-碳被选择性羟化。

In earlier work we developed a method for preparing 14-[2H]-arteether and have now employed that reaction sequence to prepare 14-[3H]-arteether. The 3H labeled arteether was used to study the mechanism of action of this group of antimalarial drugs. Infected and uninfected red blood cells were treated with labeled arteether, dihydroartemisinin and a third drug that also contains the same endoperoxide grouping. The same six proteins were found to react in infected cells, whereas none of the proteins in the uninfected red cells reacted with these compounds nor with a control, [3H]- desoxyarteether. These findings make it possible to identify, purify and study the structure and function of the reactive proteins. Diastereofacial additions of primary alcohols to the carbon-carbon double bond of anhydrodihydroartemisinin, catalyzed by triphenyl-phosphine hydrobromide, were employed to prepare a series of 11- epidihydroartemisinin derivatives. These additions enabled us to prepare previously unknown epimeric arteethers. The antimalarial activity of 11- epi-dihydroartemisinin was examined and found to be half as active as the isomer with the natural configuration at C-11. A study of minor reaction products as a function of the number of equivalents of alcohol employed, provided invaluable information on the mechanism of the reaction and on the stereochemistry of the reaction using Polarized c-Frontier Molecular Orbital Theory. Our study of the regio- and stereo-selectivity of Beauveria sulfurescens mediated hydroxylation of 1,4-disubstituted benzenes have shown that the beta-carbon of the alkyl side chain is selectively hydroxylated.