Electronically stabilized versions of the antimalarial acetal trioxanes artemether and artesunate.
From 9-substituted DHA, several new artemisinin-derived C-10 acetal ethers and esters were prepared with either a 9-fluoro or a 9-sulfonyl substituent. The very strong inductive electron-withdrawing C-9 substituent is shown to retard considerably C-10 ionization (acid-promoted etherification) of 9-fluoro-DHA and 9-sulfonyl-DHA.
Posner
Gary H
GH
Department of Chemistry, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA. ghp@jhu.edu
Maio
William A
WA
Kalinda
Alvin S
AS
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D000077332:Artesunate; D004583:Electrons; D051379:Mice; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D000077549:Artemether