Efficient preparations of the beta-glucuronides of dihydroartemisinin and structural confirmation of the human glucuronide metabolite.
New and greatly improved preparations of the 12alpha,1'beta- (5) and 12beta,1'beta- (6) glucuronides of dihydroartemisinin (DHA, 2) are reported using anomeric hydroxy and imidate glucuronate intermediates. Comparison of the synthetic and natural materials shows that the human metabolite of DHA is the 12alpha-epimer 5.
O'Neill
P M
PM
Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 3BX, UK.
Scheinmann
F
F
Stachulski
A V
AV
Maggs
J L
JL
Park
B K
BK
D000962:Antimalarials / Q000378:metabolism; D037621:Artemisinins; D002853:Chromatography, Liquid; D020719:Glucuronides / Q000138:chemical synthesis* / Q000737:chemistry / Q000652:urine; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D013237:Stereoisomerism
D000962:Antimalarials; D037621:Artemisinins; D020719:Glucuronides; D012717:Sesquiterpenes; C425787:dihydroartemisinin beta-glucuronide; C039060:artenimol