Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR.

نویسندگان

  • Songnian Lin
  • Zhi-Qiang Yang
  • Benjamin H B Kwok
  • Michael Koldobskiy
  • Craig M Crews
  • Samuel J Danishefsky
چکیده

A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an alpha-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues can retain the full potency of proteasome inhibition.

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عنوان ژورنال:
  • Journal of the American Chemical Society

دوره 126 20  شماره 

صفحات  -

تاریخ انتشار 2004