Total Synthesis and Biological Investigation of (−)‐Artemisinin: The Antimalarial Activity of Artemisinin Is not Stereospecific

Krieger, Johannes; Smeilus, Toni; Kaiser, Marcel; Seo, Ean‐Jeong; Efferth, Thomas; Giannis, Athanassios

doi:10.1002/anie.201802015

Cited by 37 publications

(28 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our synthesis (Scheme 1) started from the known and readily available aldehyde 3 [14] which was treated with the organolithium species obtained from derivative 4 [15] and n -BuLi to yield derivative 5 . The latter afforded allylic alcohol 6 after reduction of the propargylic moiety with Red-Al.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, we evaluated the antimalarial activity of (+)-3-hydroxymethylartemisinin ( 2 ) as well as of the derivatives 16 and 18 against the drug-sensitive P. falciparum NF54 strain as described previously [14]. We found them to be inactive.…”

Section: Resultsmentioning

confidence: 99%

“…However, the variety of these derivatives is limited as all of them are produced modifying the artemisinin skeleton at the same positions due to intrinsic synthetic challenges. Recently, we reported a biomimetic artemisinin synthesis that addresses these challenges and pave the way for derivatization of the (+)-artemisinin skeleton at positions not accessible using current methodology [14]. Based on our approach we report here on the synthesis and biological activity of the title compound (+)-3-hydroxymethylartemisinin ( 2 , Fig.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

Smeilus¹,

Mousavizadeh²,

Krieger³

et al. 2019

Beilstein J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

Herein, we describe a biomimetic entry to (+)-3-hydroxymethylartemisinin (2) as well as to the artemisinin derivatives (+)-3-hydroxymethyl-9-desmethylartemisinin (16) and (+)-3-hydroxymethyl-9-epi-artemisinin (18), starting from the known and readily available chiral aldehyde 3 and alkyne 4. Subsequently, the synthesized compounds have been evaluated for their antimalarial activity against the drug-sensitive P. falciparum NF54 strain. All of them were inactive. In addition, they did not show any toxicity against L6 cells (a primary cell line derived from rat skeletal myoblasts). These results contribute to a better understanding of artemisinins mechanism of action.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

Smeilus¹,

Mousavizadeh²,

Krieger³

et al. 2019

Beilstein J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…On a different note, Krieger et al synthesized synthetic enantiomer, (−)-artemisinin, and showed that the antimalarial activity of artemisinin is not stereospecific (Table 1 ) [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Antimalarial and anticancer properties of artesunate and other artemisinins: current development

Khanal

2021

Monatsh Chem

View full text Add to dashboard Cite

Graphic abstract This review provides a recent perspective of artesunate and other artemisinins as antimalarial drugs and their uses in cancer therapy. Artesunate is an artemisinin derivative. Artemisinin is extracted from the plant Artemisia annua. Artemisinin and its derivatives have been the most useful drug for malarial treatment in human history. The artesunate has an advantage of a hydrophilic group over other artemisinins which makes it a more potent drug. On the industrial scale, artemisinins are synthesized in semisynthetic ways. The 1,2,4-endoperoxide bridge of artemisinins is responsible for the drug's antimalarial activity. There is the emergence of artemisinin resistance on Plasmodium falciparum and pieces of evidence suggest that it is mainly due to the mutation at Kelch13 protein of P. falciparum . Clinical trial data show that the artesunate is more favorable than quinine and other artemisinins to treat patients with severe malaria. Pieces of evidence indicate that artemisinins can be developed as anticancer drugs. The mechanism of actions on how artemisinins act as an anticancer drug involves oxidative stress, DNA damage and repair, and various types of cell deaths.

show abstract

“…The enantiomer 9 of the natural antimalarial sesquiterpenoid artemisinin has been synthesised and shown to have the same antimalarial activity as the natural isomer. 8 Four antibacterial sesquiterpene-α-amino acid hybrids, such as stereumamide A 10, have been isolated from the mushroom Stereum hirsutum. 9 The stereumamides are the first examples of sesquiterpenoid-α-amino acid quaternary ammonium salts from natural sources.…”

mentioning

confidence: 99%