Synthesis of new artemisinin analogues from artemisinic acid modified at C-3 and C-13 and their antimalarial activity.
Artemisinic acid (2) was modified through allylic oxidation at C-3 or conjugate addition at C-13 to afford 12 methyl artemisinate derivatives (4-15). Photooxidation of the derivatives yielded eight new artemisinin analogues, including 13-cyanoartemisinin (16), 13-methoxycarbonyl artemisinin (17), 13-methoxyartemisinin (18), 13-ethylsulfonylartemisinin (19), 13-nitromethylartemisinin (20), 13-(1-nitroethyl)artemisinin (21), (3R)-3-hydroxyartemisinin (22), and (3R)-3-acetoxyartemisinin (23). Among the analogues, only compound 20 had antimalarial activity comparable to artemisinin (1).
Han
J
J
Graduate School of Agricultural Biotechnology, Seoul National University, Suwon 441-744, Korea.
Lee
J G
JG
Min
S S
SS
Park
S H
SH
Angerhofer
C K
CK
Cordell
G A
GA
Kim
S U
SU
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D037621:Artemisinins; D002738:Chloroquine / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D004352:Drug Resistance, Microbial; D004365:Drugs, Chinese Herbal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D007624:KB Cells; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000962:Antimalarials; D037621:Artemisinins; D004365:Drugs, Chinese Herbal; D012717:Sesquiterpenes; C047721:artemisic acid; D002738:Chloroquine; C031327:artemisinin