Synthesis and antimalarial activities of fluoroalkyl derivatives of dihydroartemisinin.
Fluoroalkyl ethers (4) of dihydroartemisinin (2) have been prepared by reaction of fluoroalkyl alcohols with dihydroartemisinin by different methods (BF3,Et2O or TMSCl catalysis or Mitsunobu reaction). Ethers 4a-d derived from primary fluoroalkyl alcohols were obtained in moderate to good yields by these methods. Ethers 4e-j have been prepared from fluoroalkyl secondary and tertiary alcohols and phenol using the Mitsunobu reaction. Although in vitro antimalarial activities of ethers toward Plasmodium falciparum W-2 asiatic strain are moderate, in vivo activities against Plasmodium berghei (NT 173) are excellent.
Thanh Nga
T T
TT
Institut de Chimie Industrielle, Rue Pham Ngu Lao, Hanoi, Vietnam.
Ménage
C
C
Bégué
J P
JP
Bonnet-Delpon
D
D
Gantier
J C
JC
Pradines
B
B
Doury
J C
JC
Thac
T D
TD
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins; D004353:Drug Evaluation, Preclinical; D005260:Female; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C039060:artenimol