Synthesis of a peroxime proliferator activated receptor (PPAR) alpha/gamma agonist via stereocontrolled Williamson ether synthesis and stereospecific S(N)2 reaction of S-2-chloro propionic acid with phenoxides

Aikins, JA;Haurez, M;Rizzo, JR;Van Hoeck, JP;Houpis, IN;et.al.
(2005) The Journal of Organic Chemistry — Vol. 70, n° 12, p. 4695-4705 (2005)

Files

pdfdocument.pdf
  • Restricted Access
  • Adobe PDF
  • 420.48 KB
Request a copy

Details

Authors
  • Aikins, JA
    Author
  • Haurez, M
    Author
  • Rizzo, JR
    Author
  • Van Hoeck, JP
    Author
  • Houpis, IN
    Author
Show more
Abstract
The stereospecific synthesis of the PPAR alpha/gamma agonist I was accomplished via ethylation of the optically pure tribydroxy derivative 6, itself derived via an enzymatic resolution. The ethylation can be accomplished without epimerization only under strict control of the reaction conditions and the choice of base (sodium tert-amylate), temperature (-30 degrees C), order of addition, and solvent (DMF). The key diastereospecific S(N)2 reaction of the phenol 4 with S-2-chloropropionic acid is best achieved via the sodium phenoxide of 4 derived from Na-0 as the reagent of choice. The structure elucidation and key purification protocols to achieve pharmaceutical purity will also be described.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Aikins, J., Haurez, M., Rizzo, J., Van Hoeck, J., Brione, W., Kestemont, JP., Stevens, C., Lemair, X., Stephenson, G., Marlot, E., Forst, M., & Houpis, I. (2005). Synthesis of a peroxime proliferator activated receptor (PPAR) alpha/gamma agonist via stereocontrolled Williamson ether synthesis and stereospecific S(N)2 reaction of S-2-chloro propionic acid with phenoxides. The Journal of Organic Chemistry, 70(12), 4695-4705. https://doi.org/10.1021/jo050268e (Original work published 2005)