105231-07-0Relevant academic research and scientific papers
METHOD AND DEVICE FOR THE SYNTHESIS OF ARTEMISININ
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Page/Page column 78; 79, (2013/03/28)
The present invention is directed to a method for producing artemisinin having the formula (6) from dihydroartennisinic acid in a continuous flow reactor using singlet oxygen as well as to the continuous flow reactor for producing artemisinin.
A continuous-flow process for the synthesis of artemisinin
Kopetzki, Daniel,Levesque, Francois,Seeberger, Peter H.
, p. 5450 - 5456 (2013/05/22)
Isolation of the most effective antimalarial drug, artemisinin, from the plant sweet wormwood, does not yield sufficient quantities to provide the more than 300 million treatments needed each year. The high prices for the drug are a consequence of the unreliable and often insufficient supply of artemisinin. Large quantities of ineffective fake drugs find a market in Africa. Semisynthesis of artemisinin from inactive biological precursors, either dihydroartemisinic acid (DHAA) or artemisinic acid, offers a potentially attractive route to increase artemisinin production. Conversion of the plant waste product, DHAA, into artemisinin requires use of photochemically generated singlet oxygen at large scale. We met this challenge by developing a one-pot photochemical continuous-flow process for the semisynthesis of artemisinin from DHAA that yields 65 % product. Careful optimization resulted in a process characterized by short residence times. A method to extract DHAA from the mother liquor accumulated during commercial artemisinin extractions, a material that is currently discarded as waste, is also reported. The synthetic continuous-flow process described here is an effective means to supplement the limited availability of artemisinin and ensure increased supplies of the drug for those in need. Copyright
The mechanism of the spontaneous autoxidation of dihydroartemisinic acid
Sy, Lai-King,Brown, Geoffrey D
, p. 897 - 908 (2007/10/03)
Dihydroartemisinic acid undergoes slow spontaneous autoxidation to artemisinin and other natural products, which have been reported from the medicinal plant Artemisia annua. The mechanism of this complex transformation is shown to involve four steps: (i) initial reaction of the Δ4.5-double bond of dihydroartemisinic acid with molecular oxygen, (ii) Hock cleavage of the resulting tertiary allylic hydroperoxide; (iii) oxygenation of the enol product from Hock cleavage; and (iv) cyclization of the resulting vicinal hydroperoxyl-aldehyde to the 1,2,4-trioxane system of artemisinin.
The role of the 12-carboxylic acid group in the spontaneous autoxidation of dihydroartemisinic acid
Sy, Lai-King,Brown, Geoffrey D
, p. 909 - 923 (2007/10/03)
Three of the four steps in the slow spontaneous autoxidation of dihydroartemisinic acid to artemisinin ('ene-type' reaction of molecular oxygen with the Δ4,5 double bond, Hock cleavage of the resulting tertiary allylic hydroperoxide, oxygenation of the enol product from Hock cleavage and cyclization of the resulting vicinal hydroperoxyl-aldehyde to the 1,2,4-trioxane system of artemisinin) are shown to be assisted by the proximity of the 12-carboxylic acid functional group in dihydroartemisinic acid to the functional groups participating in these reactions.
