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A Concise Synthesis of (+)-Artemisinin
CHEM635
Yinzhi FangGroup C
February 26, 2013
Chunyin Zhu and Silas P. Cook J. Am. Chem. Soc., 2012, 134 (33), pp 13577–13579
Silas P. Cook
• Education: • B.A. Reed College (1999); • Ph.D. Columbia University (2006) Supervisor:Samuel J. Danishefsky; • Postdoctoral Fellow Harvard University (2006-2008) Eric Jacobsen;
• In 2009, Silas began his independent appointment in the Chemistry Department at Indiana University, Bloomington.
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(+)-Artemisinin
• also known as Qinghaosu (Chinese: 青蒿素), and its derivatives are a group of drugs that possess the most rapid action of all current drugs against Plasmodium falciparum malaria
• The starting compound artemisinin is isolated from the plant Artemisia annua, sweet wormwood, a herb employed in Chinese traditional medicine.
• Recent advances in flow chemistry and photochemistry have highlighted an efficient method for the synthesis of artemisinin from its more plentiful biosynthetic precursor artemisinic acid, which is reduced to dihydroartemisinic acid before reacting it with singlet oxygen
• —Wiki
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Some Highlights
1.Zinc enolate alkylation
2.Unconventional [4+2] reaction
3.Singlet Oxygen Oxidation
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Zinc enolate alkylation
Jarugamilli, G. K.; Zhu, C.; Cook, S. P. Eur. J. Org. Chem. 2012, 1712–1715.
Singlet Oxygen Oxidation
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Proposed Mechanism
OH
CH3H3CO OTIPS
CH3
CH3
O1O2
OH
CH3
H3CO OTIPS
CH3
CH3
O
OO
OH
CH3
H3CO OTIPS
CH3
CH3
O
O
O
OH
CH3H3CO OTIPS
CH3
O
H
H3C
H
OO
OH
CH3
H3CO OTIPS
CH3
CH3
O
O
O
perepoxide
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Conclusion
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A cost-e ective total synthesis of (+)-artemisinin has been achieved on a gram ffscale from a widely available, inexpensive starting material, cyclohexenone.