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

Songnian Lin, Zhi Qiang Yang, Benjamin H.B. Kwok, Michael Koldobskiy, Craig M. Crews, Samuel J. Danishefsky

Research output: Contribution to journalArticlepeer-review

Abstract

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 α-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.

Original languageEnglish (US)
Pages (from-to)6347-6355
Number of pages9
JournalJournal of the American Chemical Society
Volume126
Issue number20
DOIs
StatePublished - May 26 2004
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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