216963-49-4

Upstream product

• 81496-81-3 dihydroartesiminin 
• 63968-64-9 C₁₂H₁₃O₂(CH₃)3(O)(OO) 
• 71939-50-9 dihydroartemisinin 
• 6908-41-4 4-(methoxycarbonyl)benzyl alcohol 
• 216963-48-3 methyl p-<(10-dihydroartemisininoxy)methyl>benzoate 

Relevant academic research and scientific papers

Antimalarial Activity of New Water-Soluble Dihydroartemisinin Derivatives

The usefulness of sodium artesunate (3), a water-soluble derivative of artemisinin (1), is impaired by its poor stability in aqueous solution.To overcome the ease of hydrolysis of the ester group in 3, a new series of derivatives of dihydroartemisinin (2) was prepared in which the solubilizing moiety, which contains a carboxylate group, is joined to dihydroartemisinin by an ether rather than an ester linkage.The new derivatives were prepared in good yield by treatment of dihydroartemisinin with an appropriate alcohol under boron trifluoride etherate catalysis at room temperature.All major condensation products are the β isomer.Hydrolysis of the esters with 2.5percent KOH/MeOH gave the corresponding pottassium salts, which were converted to free acids (8b-d) by acidification.The derivatives were tested in vitro against two clones of human malaria, Plasmodium falciparum D-6 (Sierra Leone clone) and W-2 (Indochina clone).No cross-resistance to the antimalarian agents mefloquine, chloroquine, pyrimethamine, sulfadoxine, and quinine was observed.In general, the new compounds are more effective against the W-2 than the D-6 strain.Esters (5a-d) possess activity comparable to that of the parent compounds 1 and 2; however, conversion of the esters to their corresponding carboxylates (7a-d) or acids (8a-d), with the exception of artelinic acid (8d), drastically decreases the antimalarial activities in both cell lines.Artelinic acid, which is both soluble and stable in 2.5percent K2CO3 solution, possesses superior in vivo activity against Plasmodium berghei than artemisinin or artesunic acid.

Synthesis, Antiplasmodial, and Antileukemia Activity of Dihydroartemisinin–HDAC Inhibitor Hybrids as Multitarget Drugs

Artemisinin-based combination therapies (ACTs) are the gold standard for the treatment of malaria, but the efficacy is threatened by the development of parasite resistance. Histone deacetylase inhibitors (HDACis) are an emerging new class of potential antiplasmodial drugs. In this work, we present the design, synthesis, and biological evaluation of a mini library of dihydroartemisinin–HDACi hybrid molecules. The screening of the hybrid molecules for their activity against selected human HDAC isoforms, asexual blood stage P. falciparum parasites, and a panel of leukemia cell lines delivered important structure–activity relationships. All synthesized compounds demonstrated potent activity against the 3D7 and Dd2 line of P. falciparum with IC50 values in the single-digit nanomolar range. Furthermore, the hybrid (α)-7c displayed improved activity against artemisinin-resistant parasites compared to dihydroartemisinin. The screening of the compounds against five cell lines from different leukemia entities revealed that all hydroxamate-based hybrids (7a–e) and the ortho-aminoanilide 8 exceeded the antiproliferative activity of dihydroartemisinin in four out of five cell lines. Taken together, this series of hybrid molecules represents an excellent starting point toward the development of antimalarial and antileukemia drug leads.

Process for one pot conversion of artemisinin into artelinic acid

The present invention relates to an improved process for one pot conversion of artemisinin into artelinic acid, which reduces the three step (three pot) conversion of artemisinin to artelinic acid in one step (one pot). The process of preparation of artel