ARTEETHER

 

Molecular Formula:

C₁₇H₂₈O₅

CAS Registry Number:

109716-83-8
beta-Arteether, Artemotil, Arteether, SM-227, E MAL, Artecef

 Arteether;10-Ethoxydecahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin;beta-Artether;3,12-Epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin, 10-ethoxydecahydro-3,6,9-trimethyl-

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Reduction of artemisinin (I) with sodium borohydride provides dihydroartemisinin (II) (1-5). Subsequent treatment of hemiacetal (II) with ethanol in the presence of acid catalysts, such as BF3稥t2O (1), ClSiMe3 (2), p TsOH (6-8), AlCl3 (7, 8) or cation-exchange resins (3, 7, 8) gives rise to the target beta-ethoxy acetal as the major diastereoisomer. Alternatively, dihydroartemisinin (II) is first dehydrated to the enol ether (III) employing P2O5 in CH2Cl2. Addition of EtOH to (III) in the presence of PPh3稨Br then produces a mixture of the target compound and its 11-alpha epimer (IV), along with minor amounts of their 12-alpha ethoxy analogues (4). The analogous synthesis employing EtO2H or EtO3H yields the corresponding 11-deuterium or 11-tritium labelled compounds (9).



 Condensation of dihydroartemisinin (I) with ethyl glycolate in the presence of BF3稥t2O in anhydrous diethyl ether produces a mixture of the desired glycolate adduct (II) along with the title ethoxy derivative as a byproduct (5).







Reduction of qinghaosu (artemisine) (I) by means of sodium borohydride gives a hemiacetal, artemisininelactol (II). Interaction of the latter compound with methanol in the presence of boron triftuoride gives artemether. It can be prepared even more easily by treating artemisininelactol with methanol in acidic medium. The epimers can be separated by chromatography. However, the product without separation of epimers has been used for clinical studies.


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