二氢青蒿素和11－羟基二氢青蒿素的酯类衍生物的合成

Synthesis of esters of Dihydroartemisinin and 11,12-Dihydroxyartemisinin

为寻找抗疟活性更高和化学性质更稳定的青蒿素衍生物，合成了７个二氢青蒿素和１１－羟基二氢青蒿素的酯类衍生物并进行了鼠疟筛选。（４ａ）和（４ｂ）的抗疟活性与青蒿素相当，而５ａ－５ｅ则远不如青蒿素本身。这一实验结果说明１１－羟基的引入导致抗疟活性的下降，经长期的稳定性观察，发现这些酯类衍生物中大体积取代基团的存在有利于它们的稳定。

In order to search for new derivatives of artemisinin with more stability and higher antimalarial activity,7 esters of dihydroartemisinin and 11α-hydroxy 12-dihydroartemisinin were synthesized and tested in mice against chloroquine-resistant P.berghhei.On the basis of the observation of their stability,the bulky substituent groups were considered to be favorable to stability of these compounds.While 4a～4b were showed to be active as artemisinin,the derivatives of 11,12-dihydroxyartemisinin,5a～5e,were considerably less active than was artemisinin.It demonstrated that introduction of a hydroxy group into 11-position resulted in reduction of antimalarial activity.