Venugopalan B, Bapat C P, Karnik P J, Chatterjee D K, Iyer N, Lepcha D
Department of Chemistry, Hoechst India Ltd., Mulund, Bombay, India.
J Med Chem. 1995 May 26;38(11):1922-7. doi: 10.1021/jm00011a012.
Bromoacetal 2 undergoes a novel ring-contracted reaction to give the aldehyde 3 in the presence of DBU or triethylamine. The aldehyde 3 is reduced to the alcohol 4 and oxidized to the carboxylic acid 5. The alcohol 4 reacts with dihydroartemisinin to give the two diastereoisomers 38 and 39. All the compounds were tested for antimalarial activity in mice infected with chloroquine sensitive Plasmodium berghei. If the activity of a compound was comparable to that of the standard compound, such as arteether, it was tested against chloroquine resistant NS strain infection in mice. Initially the compounds were administered subcutaneously, and if found to be active, they were tested by oral route. The antimalarial activity of compounds 19, 38, and 39 was found to be comparable to that of arteether when tested in K-173-infected mice. They were also active against chloroquine resistant NS strain infection in mice.
在1,8-二氮杂双环[5.4.0]十一碳-7-烯（DBU）或三乙胺存在下，溴代缩醛2发生一种新型的环收缩反应生成醛3。醛3被还原为醇4并被氧化为羧酸5。醇4与二氢青蒿素反应生成两个非对映异构体38和39。对所有化合物在感染氯喹敏感伯氏疟原虫的小鼠中进行抗疟活性测试。如果一种化合物的活性与标准化合物（如蒿乙醚）相当，则对其在感染氯喹抗性NS株的小鼠中进行测试。最初化合物通过皮下给药，如果发现有活性，则通过口服途径进行测试。在感染K - 173的小鼠中测试时，发现化合物19、38和39的抗疟活性与蒿乙醚相当。它们对感染氯喹抗性NS株的小鼠也有活性。
