Efficient preparations of the beta-glucuronides of dihydroartemisinin and structural confirmation of the human glucuronide metabolite

P M O'Neill; F Scheinmann; A V Stachulski; J L Maggs; B K Park

doi:10.1021/jm001061a

Efficient preparations of the beta-glucuronides of dihydroartemisinin and structural confirmation of the human glucuronide metabolite

J Med Chem. 2001 Apr 26;44(9):1467-70. doi: 10.1021/jm001061a.

Authors

P M O'Neill¹, F Scheinmann, A V Stachulski, J L Maggs, B K Park

Affiliation

¹ Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 3BX, UK.

PMID: 11311070
DOI: 10.1021/jm001061a

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimalarials / metabolism
Artemisinins*
Chromatography, Liquid
Glucuronides / chemical synthesis*
Glucuronides / chemistry
Glucuronides / urine
Humans
Malaria, Falciparum / drug therapy
Malaria, Falciparum / metabolism
Male
Mass Spectrometry
Sesquiterpenes / chemical synthesis*
Sesquiterpenes / chemistry
Sesquiterpenes / metabolism
Sesquiterpenes / urine
Stereoisomerism

Substances

Antimalarials
Artemisinins
Glucuronides
Sesquiterpenes
dihydroartemisinin beta-glucuronide
artenimol