155489-63-7Relevant academic research and scientific papers
Synthesis, Conformational Analysis, and Antimalarial Activity of Tricyclic Analogs of Artemisinin
Avery, Mitchell A.,Gao, Fenglan,Chong, Wesley K. M.,Hendrickson, Thomas F.,Inman, Wayne D.,Crews, Phillip
, p. 957 - 972 (2007/10/02)
Aspects of synthesis, conformational analysis, and antimalarial activity of artemisinin analogs (+/-)-5-nor-6-desmethyl-4,5-secoartemisinin (2), (-)-5-nor-4,5-secoartemisinin (3), (+)-4,5-secoartemisinin (4), and (+)-4,5-desethano-artemisinin (5) are described.The conformations of these multicyclic structures were determined through a combination of X-ray crystallography, NMR, and computational analysis, with an emphasis on the 1,2,4-trioxane geometry.Two major solution conformations for both 2 and 3 were found: all chair forms 2a and 3a, and twist-boat/twist-boat/chair forms 2b and 3b, respectively.The major solution conformer 2a matched the solid state structure found via X-ray crystallography.Computations suggest that (+)-4,5-Secoartemisinin (4) has three conformations of equal energy: chair/twist-boat/boat, 4a, twist-boat/twist-boat/chair, 4b, corresponding to the X-ray crystal structure, and twist boat/chair/chair, 4c.The 1,2,4-trioxane and lactone rings adopt the twist-boat conformations in 2b, 3b, 4a, and 4c.When compared to artemisinin, these tricyclic, flexible analogs have different geometry yet retain some in vitro antimalarial activity against resistant strains of Plasmodium falciparum.Possible structure/ activity correlations are discussed.
