154698-10-9Relevant academic research and scientific papers
C-16 artemisinin derivatives and their antimalarial and cytotoxic activities: Syntheses of artemisinin monomers, dimers, trimers, and tetramers by nucleophilic additions to artemisitene
Ekthawatchai,Kamchonwongpaisan,Kongsaeree,Tarnchompoo,Thebtaranonth,Yuthavong
, p. 4688 - 4695 (2001)
Nucleophilic additions of lithium keto and ester enolates and mono- and bifunctional Grgnard reagents to artemisitene provided C-16-derived artemisinin monomers, dmers, trimers, and tetramers whose antimalarial and cytotoxic have been evaluated.
Structure-activity relationships of the antimalarial agent artemisinin. 7. Direct modification of (+)-artemisinin and in vivo antimalarial screening of new, potential preclinical antimalarial candidates
Avery, Mitchell A.,Alvim-Gaston, Maria,Vroman, Jeffrey A.,Wu, Baogen,Ager, Arba,Peters, Wallace,Robinson, Brian L.,Charman, William
, p. 4321 - 4335 (2007/10/03)
On the basis of earlier reported quantitative structure-activity relationship studies, a series of 9β-16-(arylalkyl)-10-deoxoartemisinins were proposed for synthesis. Several of the new compounds 7 and 10-14 were synthesized employing the key synthetic intermediate 23. In a second approach, the natural product (+)-artemisinic acid was utilized as an acceptor for conjugate addition, and the resultant homologated acids were subjected to singlet oxygenation and acid treatment to provide artemisinin analogues. Under a new approach, we developed a one step reaction for the interconversion of artemisinin 1 into artemisitene 22 that did not employ selenium-based reagents and found that 2-arylethyliodides would undergo facile radical-induced conjugate addition to the exomethylene lactone of 22 in good yield. The lactone carbonyls were removed sequentially by diisobutylaluminum hydride reduction followed directly by a second reduction (BF3-etherate/Et3SiH) to afford the desired corresponding pyrans. Six additional halogen-substituted aromatic side chains were installed via 22 furnishing the bioassay candidates 15-20. The analogues were examined for in vitro antimalarial activity in the W-2 and D-6 clones of Plasmodium falciparum and were additionally tested in vivo in Plasmodium berghei- and/or Plasmodium yoelii-infected mice. Several of the compounds emerged as highly potent orally active candidates without obvious toxicity. Of these, two were chosen for pharmacokinetic evaluation, 14 and 17.
Structure-Activity Relationships of the Antimalarial Agent Artemisinin. 1. Synthesis and Comparative Molecular Field Analysis of C-9 Analogs of Artemisinin and 10-Deoxoartemisinin
Avery, Mitchell A.,Gao, Fenglan,Chong, Wesley K. M.,Mehrotra, Sanjiv,Milhous, Wilbur K.
, p. 4264 - 4275 (2007/10/02)
A series of C-9 β-substituted artemisinin analogs (2-21) were synthesized via dianion alkylation of the total synthetic intermediate 57 followed by subsequent ozonolysis/acidification, or by alkylation of the enolate derived from (+)-9-desmethylartemisini
