233282-43-4Relevant academic research and scientific papers
Asymmetric syntheses of enantiomeric 3-p-fluorophenyl 1,2,4-trioxane analogues of the antimalarial artemisinin
O' Neill, Paul M.,Miller, Alison,Bickley, Jamie F.,Scheinmann, Feodor,Oh, Chang Ho,Posner, Gary H.
, p. 9133 - 9136 (2007/10/03)
We have devised an asymmetric synthesis of chiral artemisinin analogues (+)-4a and (-)-4a that retain the tricyclic ring system found in the natural product. The key step in the preparation of (+)-4a involves an asymmetric MgCl2 promoted Michael addition of the (R)-(-)pyrrolidinemethanol-derived enamine 8 to acrylonitrile. This gives the corresponding ketone 9 in 50% yield (>95% ee). Subsequent elaboration of 9 provides the trioxane target (+)-4a in greater than 85% ee. Enantiomeric trioxane (-)-4a was prepared in a similar manner using (S)-(+)-pyrrolidinemethanol in the first step of the sequence.
