Arteether Chemical Properties

Melting point:

80-820C

alpha 

D21 +154.5° (c = 1.0 in CHCl3)

Boiling point:

372.4±42.0 °C(Predicted)

Density 

1.16±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,2-8°C

solubility 

Chloroform (Slightly), Ethyl Acetate (Slightly)

form 

Solid

color 

White

optical activity

[α]/D +148 to +165°, c =1 in chloroform-d

InChI

InChI=1S/C17H28O5/c1-5-18-14-11(3)13-7-6-10(2)12-8-9-16(4)20-15(19-14)17(12,13)22-21-16/h10-15H,5-9H2,1-4H3/t10-,11-,12+,13+,14+,15-,16-,17-/m1/s1

InChIKey

NLYNIRQVMRLPIQ-XQLAAWPRSA-N

SMILES

O1[C@]23[C@@]4([H])O[C@@](C)(CC[C@@]2([H])[C@H](C)CC[C@@]3([H])[C@@H](C)[C@@H](OCC)O4)O1

CAS DataBase Reference

75887-54-6

Arteether Usage And Synthesis

Description

Arteether reached the market in the Netherlands as a solution in sesame oil, administered by i.m. injection, for the treatment of severe malaria infections in children and adolescents. Artheether, a sesquiterpene acetal with an endoperoxide bridge, is an ether derivative of the naturally occuring compound artemisinin, the active component of Chinese herbal remedies. As the other structural analogs of artemisinin, such as artesunate or artemether, it acts rapidly against Plasmodium, the parasite responsible for the disease, during the early blood stage of its development. It also exhibits a gametocytocidal activity against Plasmodium falciparum, reducing its potential for transmission. Because the only controlled clinical studies had been performed in children and adolescents, this new antimalarial drug was only approved for young patients. Further studies in adults treated with 150 mg i.m. artemotil, once daily for three consecutive days, indicated that the drug was efficient, rapidly acting (parasite clearance time meanly 38 h) and well tolerated. A new promising achievement in the regression of malaria is the combination of artemisinin derivatives with other long-lived antimalarials as mefloquine or pyrimethamine/sulfa.

Chemical Properties

White Crystalline Solid

Originator

Central Drug Research Institute (India)

Uses

Derivative of Artemisinin. Antimalarial

Definition

ChEBI: Artemotil is an artemisinin derivative.

brand name

Artemotil

Synthesis

The general procedure for the synthesis of (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-ethoxy-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isobenzofuran from artemisinin (CAS: 108739-44-2) was as follows: Example 1: Artemisinin (1.0 g) was dissolved in ethanol (20 mL) with polyhydroxy catalyst dextrose (5.0 g) and stirred at room temperature for 5 minutes. Subsequently, sodium borohydride (600 mg) was slowly added over 10 min and the reaction mixture was stirred for about 1 h at room temperature (20-23°C). The progress of the reaction was monitored by thin layer chromatography (TLC) to confirm the completion of the reduction step. The acid catalyst chlorotrimethylsilane (3.5 mL) was slowly added at 10-23°C. The reaction mixture was continued to be stirred at room temperature for about 1 hour. Upon completion of the reaction, cooling water (about 150 mL) was added to the mixture and the aqueous phase was extracted with a hexane solution of 1% ethyl acetate (3 x 50 mL). The combined ethyl acetate-hexane extract was washed sequentially with 0.5% sodium bicarbonate solution (100 mL) and water (50 mL). The hexane extract was dried over anhydrous sodium sulfate and the solvent was evaporated to give 1.038 g of the crude product, which contained artemether and a few impurities. The crude product was purified by silica gel column chromatography (silica gel 10 g, eluent 0.5% to 8% ethyl acetate in hexane solution) to give a mixture of α and β arteether 0.86 g (yield 86% w/w). A small amount of arteether was taken to separate the α and β isomers by preparative thin layer chromatography (TLC) and characterized by co-thin layer chromatography (Co-TLC) and spectral analysis.

References

[1] Patent: US2004/106809, 2004, A1. Location in patent: Page 3
[2] Patent: US2004/106809, 2004, A1. Location in patent: Page 4
[3] Patent: US2004/106809, 2004, A1. Location in patent: Page 3-4

Arteether(75887-54-6)Related Product Information

• Tetrahydro-4H-pyran-4-one
• Sodium 1-heptanesulfonate
• 1,4-Dioxane
• Heptane
• 2-Ethoxyethanol
• Boron trifluoride diethyl etherate
• Resin epoxy
• Artemether
• tert-Amyl hydroperoxide
• tert-Butyl hydroperoxide
• CYCLOHEPTANE
• DHQHS 2
• Dihydroartemisinin
• Diethyl ether
• artesunate
• EPOXY
• Deoxy Arteether
• Arteether