青蒿砜-氨基二硫代甲酸酯类化合物的合成

Syntheses of Artemisone-aminodithioformate Hybrid Compounds

以双氢青蒿素(DHA)为原料,与草酰氯发生酰化反应,然后经硫代吗啉取代反应、双氧水氧化反应得到青蒿砜1,由1经过烷基化反应、脱硅保护基和碘代反应得到青蒿砜-碘代物2α;以三乙胺为催化剂,2α与哌嗪类化合物、CS_2在"一锅煮"条件下得到青蒿砜-氨基二硫代甲酸酯化合物(3a^3d)。所有目标化合物的结构均经~1H NMR、^(13)C NMR、IR和HR-ESI-MS得到确证。

A practical preparation of artemisone-aminodithioformate hybrid compounds was achieved from dihydroartemisinin and thiomorpholine. The dihydroartemisinin was treated with oxalyl chloride followed by mixing the mixture with a solution of thiomorpholine in dichloromethane,efficiently affording the artemisinin-thiomorpholine complex. Then oxidation of the raw mixture with hydrogen peroxide in the presence of sodium tungstate gave the artemisone 1 with 48% yield for three steps. The artemisone 1 was alkylated with a silyl protected 6-iodo-1-hexanol,then desilylation and iodination of the alkylate compound successfully delivered the corresponding iodide 2α,and the total yield for these three steps was 22. 1%. Finally,introduction of the piperazidines into the artemisone motif was realized with carbon disulphide as the linkage,where four artemisone-aminodithioformate hybrid compounds（ 3a ~3d） were obtained from a triethylamine promoted one-pot reaction of iodide 2α,piperazidine and carbon disulphide from room temperature to reflux. The structures of all the synthetic compounds are identified by ~1 H NMR,^（13） C NMR,IR and HR-ESI-MS.