Dihydroartemisinin acetate

A high level of activity continues in connection with the synthesis of antimalarial artemisinin analogues and congeners, in which the 1,2-dioxepane moiety is embedded. Recent examples include the syntheses of various 10-substituted deoxoartemisinins of type 123 (eg. R1 = Cl COMe) from dihydroartemisinin acetate, and of type 124 (eg. R2 = a-OH, R3 = Me), from Grignard reagent addition to 10-(2-oxoethyl)deoxoartemisinin . 

Galal AM, Gul W, Slade D, Ross SA, Feng S, Hollingshead MG Alley MC, Kaur G ElSohly MA. (2009) Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene acetal dimers showing anticancer and antiprotozoal activity. Bioorg Med Chem 17 741-751. 

Artemisinin (1) can be selectively reduced with NaBH4 to afford dihydroartemisinin (175, DHQHS), which has been shown to be roughly ten times as potent as parent material 1. The lactol DHQHS (175) was converted to various ethers by treatment in alcohols with boron trifluoride (acetal formation conditions). Notably artemether (144) and arteether (145) were prepared in this manner. Alternatively, DHQHS can be acylated to yield esters or carbonates, as shown for sodium artesunate (146) as an example. 

Reduction of (162) with sodium borohy-dride occurs at the lactone carbonyl, leaving the peroxide intact (196, 197). The resulting cyclic hemiacetal, dihydroartemisinin (155), which is a more potent antimalarial than the parent compound, shows typical acetal reac-... 

Esters (32 4, R = C(=0)-alkyl or -aryl), of which a-epimers were mainly obtained, were more active than the ethers. Sodium artesunate (32 5, R = C(=0)-CH2CH2C00Na), the half succinic acid half-ester of dihydroartemisinin is water-soluble and shows potent antimalarial activity. Therefore, this can be administered intravenously. However it is uncertain whether this derivative is pharmacologically effective because of its sensitivity to hydrolysis. In considering this result new ether derivatives of dihydroartemisinin, which are stable and water soluble derivatives have been prepared [46]. Dihydroartemisinin was condensed with esters of aliphatic or aromatic carboxylic acids with hydroxy groups to produce mainly ethers with the P-configuration. Ethyl 2-( 10-dihydroartemisininoxy) acetate (31 4, R = CH2COOCH2CH3) and methyl... 

Artemisinin and three analog antimalarials (artesunate, a- and / -dihydroartemisinin) were extracted from plasma and separated on a 35°C Cjg column (electrochemical detector, —1.0 V vs. Ag/AgCl). A 45/55 acetonitrile/water (0.1 M acetic acid at pH... 

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