Anhydrodihydroartemisinin and its 10-trifluoromethyl analogue: access to novel d-ring-contracted artemisinin trifluoromethyl ketones.
The preparation of the 10-trifluoromethyl hydroartemisinin, followed by dehydration, afforded the trifluoromethyl analogue 2 of anhydrodihydroartemisinin 1. The reactivity of these two glycals of artemisinin were compared in epoxidation and halogenation reactions. Iodination of glycal 1 in water and the further rearrangement of the produced iodo hemiacetal provided the new D-ring-contracted aldehyde 8alpha, where the methyl at C-9 is beta. Epoxidation of 10-trifluoromethyl anhydrodihydroartemisinin 2 stereoselectively provided the beta-epoxy ether 11 in high yield. When treated with hexafluoro-2-propanol or trifluoroethanol, 11 readily underwent a rearrangement yielding to the D-ring-contracted trifluoromethyl ketone 9alpha with retention of configuration at C-9.
Grellepois
Fabienne
F
BIOCIS, CNRS, Faculté de Pharmacie, Rue J.B. Clément, Châtenay-Malabry, F-92296, France.
Chorki
Fatima
F
Crousse
Benoit
B
Ourévitch
Michèle
M
Bonnet-Delpon
Danièle
D
Bégué
Jean-Pierre
JP
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry; D037621:Artemisinins; D002384:Catalysis; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C454480:10-trifluoromethylanhydrodihydroartemisinin; D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C089918:anhydrodihydroartemisinin; C031327:artemisinin