Abstract
Reaction of artemisinin (
1
) with ethanolamine, followed by acid treatment produced the lactam (4
S
,8
S
,9
S
,13
S
,1
R
,5
R
,12
R
)-11-aza-11-(2-hydroxyethyl)-1,5,9-trimethyl-14,15-dioxatetracyclo [10.2.1.0<4,13>.0<8,13>]pentadecan-10-one (
4
) and the diol (1
S
,2
S
,6
S
,7
S
,5
R
,8
R
)-4-aza-5,6-dihydroxy-4-(2-hydroxyethyl)-2,8-dimethyl-7-(3-oxo-butyl)bicyclo[4.4.0]decan-3-one (
7
). When ethylenediamine was used instead of the ethanolamine, the dimeric lactam (1
S
,4
S
,8
S
,9
S
,13
S
,5
R
,12
R
)-11-[2-((1S,4S,8S,9S,13S,5R, 12R)-11-aza-1,5,9-trimethyl-14,15-dioxa-10-oxotetracyclo[10.2.1.0<4,13>.0<8,13>] penta-dec-11-yl)ethyl]-11-aza-1,5,9-tri-methyl-14,15-dioxatetracyclo-[10.2.1.0<4,13>.0<8,13>]-pentadecan-10-one (
8
) was obtained. All compounds are new azaartemisinin derivatives lacking the peroxide functionality. These compounds were evaluated for antimalarial and cytotoxic activities. Only the dimer
8
was found to possess antimalarial activity, while only the diol
7
exhibited cytotoxic activity against human breast ductal carcinoma.