Transformation of artemisinin by Cunninghamella elegans.
Semi-synthetic derivatives of the anti-malarial drug artemisinin hold great promise in the search for an effective and economical treatment of chloroquine-resistant forms of malaria. Unfortunately, synthetic functionalization of the artemisinin skeleton is often tedious and/or impractical. We seek to utilize 7beta-hydroxyartemisinin, obtained from microbial transformation, as a semi-synthetic precursor for the synthesis of novel 7beta-substituted artemisinin anti-malarial agents. Here we employ liquid cultures of Cunninghamella elegans as a means for the rational and economical bioconversion of artemisinin to 7beta-hydroxyartemisinin in 78.6% yield. In addition, there were three other bioconversion products: 7beta-hydroxy-9alpha-artemisinin (6.0%), 4alpha-hydroxy-1-deoxoartemisinin (5.4%), and 6beta-hydroxyartemisinin (6.5%).
Parshikov
I A
IA
Department of Medicinal Chemistry, University of Mississippi, University, MS 38677-1848, USA.
Muraleedharan
K M
KM
Avery
M A
MA
Williamson
J S
JS
D000962:Antimalarials / Q000737:chemistry; D037621:Artemisinins / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned; D020093:Cunninghamella / Q000254:growth & development / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*
C519571:7-hydroxyartemisinin; D000962:Antimalarials; D037621:Artemisinins; D017077:Culture Media, Conditioned; D012717:Sesquiterpenes; C031327:artemisinin