An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction.

نویسندگان

  • Zhiguo J Song
  • Anthony O King
  • Marjorie S Waters
  • Fengrui Lang
  • Daniel Zewge
  • Matthew Bio
  • Johnnie L Leazer
  • Gary Javadi
  • Amude Kassim
  • David M Tschaen
  • Robert A Reamer
  • Thorsten Rosner
  • Jennifer R Chilenski
  • David J Mathre
  • R P Volante
  • Richard Tillyer
چکیده

An efficient asymmetric synthesis of a selective estrogen receptor modulator (SERM) that has a dihydrobenzoxathiin core structure bearing two stereogenic centers is reported. The stereogenic centers were established by an unprecedented chiral sulfoxide-directed stereospecific reduction of an alpha,beta-unsaturated sulfoxide to the saturated sulfide in one step. Studies to elucidate the mechanism for this reduction are reported. Highly efficient Cu(I)-mediated ether formation was used to install the ether side chain, and selective debenzylation conditions were developed to remove the benzyl protecting groups on the phenols.

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 101 16  شماره 

صفحات  -

تاریخ انتشار 2004