ANTIMALARIAL ACTIVITY OF NOVEL RING-CONTRACTED ARTEMISININ DERIVATIVES

Bromoacetal 2 undergoes a novel ring-contracted reaction to give the a ldehyde 3 in the presence of DBU or triethylamine. The aldehyde 3 is r educed to the alcohol 4 and oxidized to the carboxylic acid 5. The alc ohol 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 a ctivity of a compound was comparable to that of the standard compound, such as arteether, it was tested against chloroquine resistant NS str ain infection in mice. Initially the compounds were administered subcu taneously, 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. Th ey were also active against chloroquine resistant NS strain infection in mice.