Bio-transformation of artemisinin using soil microbe: Direct C-acetoxylation of artemisinin at C-9 by Penicillium simplissimum

Biotransformation of artemisinin by Aspergillus niger

“…There are many reports on microbial transformation of artemisinin. These transformations usually include the following metabolic processes: hydroxylation, deoxidation, and acetoxylation reactions (Gaur et al 2014;Parshikov et al 2004bParshikov et al , 2006Zhan et al 2002;Goswami et al 2010). The products of the reported microbial transformations of artemisinin usually include 7β-hydroxyartemisinin, 7β-hydroxy-9α-artemisinin, 4α-hydroxy-1-deoxyartemisinin, 6β-hydroxyartemisinin, 5β-h y d r o x y a r t e m i s i n i n , 4 β -h y d r o x y a r t e m i s i n i n , deoxyartemisinin, 4β-hydroxy-1-deoxyartemisinin, 5aα-hydroxy-1-deoxyartemisinin, 4β-acetoxy artemisinin, 4α-hydroxyartemisinin, and 5aα-hydroxyartemisinin (Parshikov et al 2004b(Parshikov et al , 2006Zhan et al 2002;Goswami et al 2010;Gaur et al 2014).…”

“…So, it is important to find new and more effective antimalarial drugs by modifying the structure of artemisinin and its analogues through chemical and biological methods. Some studies on the structural modification of artemisinin by chemical and biological methods were reported (Gaur et al 2014;Parshikov et al 2004aParshikov et al , b, 2006Zhan et al 2002;Goswami et al 2010;Acton 1999).…”

Stereoselective chlorothiolation of artemisinin-derived C-10 oxa terminal alkynes

“…Accordingly, artemisinin is treated with NaBH 4 in MeOH at 0 • C to afford dihydroartemisinin 2 in 90 % yield which upon treatment with propargyl/homopropargyl alcohol in the presence of BF 3 ·OEt 2 in dichloromethane afforded artemisinin-derived terminal alkynes 5a/5b [6][7][8][9][10][11]. Initially, we attempted the chlorothiolation reaction on 5a in dichloroethane using 4-methylbenzenesulfenylchloride which was generated in situ from the reaction of 4-methylbenzenthiol with N-chlorosuccinamide [28].…”

“…Moreover, Haynes et al reported artemisone as one of the sulfur-containing second-generation derivatives of artemisinin which is now undergoing clinical trials [12]. Inspired by the potent anticancer sulfur-containing artemisinin derivatives, and in continuation of our interest in maximizing the structural diversity of artemisinin analogs to find potent anticancer agents, we wish to report the stereoselective chlorothiolation of artemisinin-derived C-10 oxa alkynes [6][7][8][9][10][11].…”

“…2). Efforts in this direction have yielded a large number of artemisinin analogs with profound anticancer or antimalarial activities, and are in different stages of clinical development [6][7][8][9][10][11][12]26].…”