113472-97-2Relevant articles and documents
Epiartemisinin, a remarkably poor antimalarial: Implications for the mode of action
Jefford, Charles W.,Burger, Ulrich,Millasson-Schmidt, Patricia,Bernardinelli, Gerald,Robinson, Brian L.,Peters, Wallace
, p. 1239 - 1246 (2000)
Epiartemisinin (7) was prepared by the base epimerization of artemisinin (1) and its structure determined by X-ray analysis. The antimalarial activity of 7 against the chloroquine-sensitive and resistant strains of Plasmodium berghei and P. yoelii in the mouse was compared with that of the highly effective schizonticide 1 and found to be drastically diminished. It is argued that the mode of action on the intraerythrocytic parasite by 7 is compromised by steric hindrance arising from the α-disposed Me group. In the initial step, intimate complexation with heme is hindered or biased to favor the formation of a less potent C-centered radical, the final lethal agent.
In vivo transformations of artemisinic acid in Artemisia annua plants
Brown, Geoffrey D.,Sy, Lai-King
, p. 9548 - 9566 (2007)
Artemisinic acid labeled with both 13C and 2H at the 15-position has been fed to intact plants of Artemisia annua via the cut stem, and its in vivo transformations studied by 1D- and 2D-NMR spectroscopy. Seven labeled metabolites have been isolated, all of which are known as natural products from this species. The transformations of artemisinic acid-as observed both for a group of plants, which was kept alive by hydroponic administration of water and for a group, which was allowed to die by desiccation-closely paralleled those, which have been recently described for its 11,13-dihydro analog, dihydroartemisinic acid. It seems likely therefore that similar mechanisms, involving spontaneous autoxidation of the Δ4,5 double bond in both artemisinic acid and dihydroartemisinic acid and subsequent rearrangements of the resultant allylic hydroperoxides, may be involved in the biological transformations, which are undergone by both compounds. All of the sesquiterpene metabolites, which were obtained from in vivo transformations of artemisinic acid retained their unsaturation at the 11,13-position, and there was no evidence for conversion into any 11,13-dihydro metabolite, including artemisinin, the antimalarial drug, which is produced by A. annua. This observation led to the proposal of a unified biosynthetic scheme, which accounts for the biogenesis of many of the amorphane and cadinane sesquiterpenes that have been isolated as natural products from A. annua. In this scheme, there is a bifurcation in the biosynthetic pathway starting from amorpha-4,11-diene leading to either artemisinic acid or dihydroartemisinic acid; these two committed precursors are then, respectively, the parents for the two large families of highly oxygenated 11,13-dehydro and 11,13-dihydro sesquiterpene metabolites, which are known from this species.
Concise synthesis of artemisinin from a farnesyl diphosphate analogue
Tang, Xiaoping,Demiray, Melodi,Wirth, Thomas,Allemann, Rudolf K.
, p. 1314 - 1319 (2017/09/30)
Artemisinin is one of the most potent anti-malaria drugs and many often-lengthy routes have been developed for its synthesis. Amorphadiene synthase, a key enzyme in the biosynthetic pathway of artemisinin, is able to convert an oxygenated farnesyl diphosphate analogue directly to dihydroartemisinic aldehyde, which can be converted to artemisinin in only four chemical steps, resulting in an efficient synthetic route to the anti-malaria drug.
METHOD AND DEVICE FOR THE SYNTHESIS OF ARTEMISININ
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Paragraph 0532, (2015/01/06)
The present invention is directed to a method for producing artemisinin having the formula from dihydroartemisinic acid in a continuous flow reactor using singlet oxygen as well as to the continuous flow reactor for producing artemisinin.
