Amino- and Hydroxy-Functionalized 11-Azaartemisinins and Their Derivatives

Abstract

An efficient conversion of artemisinin 1 into three new amino- and hydroxy-functionalized 11-aza prototypes 9, 11, and 12 has been achieved on a multigram scale by reaction with hydrazine, hydroxylamine, and 2-amino ethanol, respectively. Of these, 9 has been further diversified into a wide range of derivatives including imines, amines, amides, and linker based dimers. Prototypes 11 and 12 have been converted into the corresponding ethers in high yields. Some of these compounds have shown a high order of activity against multidrug-resistant malaria in mice by oral route.