Parshikov I A, Muraleedharan K M, Avery M A, Williamson J S
Department of Medicinal Chemistry, University of Mississippi, University, MS 38677-1848, USA.
Appl Microbiol Biotechnol. 2004 Jun;64(6):782-6. doi: 10.1007/s00253-003-1524-z. Epub 2004 Jan 21.
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%).
抗疟药物青蒿素的半合成衍生物在寻找有效且经济的耐氯喹疟疾治疗方法方面具有巨大潜力。不幸的是，青蒿素骨架的合成官能团化往往繁琐且/或不切实际。我们试图利用通过微生物转化获得的7β-羟基青蒿素作为半合成前体，用于合成新型7β-取代的青蒿素抗疟剂。在此，我们采用雅致小克银汉霉的液体培养物，作为将青蒿素合理且经济地生物转化为7β-羟基青蒿素的手段，产率为78.6%。此外，还有其他三种生物转化产物：7β-羟基-9α-青蒿素（6.0%）、4α-羟基-1-脱氧青蒿素（5.4%）和6β-羟基青蒿素（6.5%）。
