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

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

Journal of the American Chemical Society (2004-05-20)

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

ABSTRAKT

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.

MATERIAŁY

Numer produktu

Marka

Opis produktu

379670

Sigma-Aldrich

[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane