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Publication 62  

  1. Divergent Syntheses of Resorcylic Acid Lactones: L-783277, LL-Z1640-2, and Hypothemycin
    P.-Y. Dakas, R. Jogireddy, G. Valot, S. Barluenga, N. Winssinger
    Chem. Eur. J. 2009, 15, 11490-11497

Extension of the scope of the sulfide linker to access all the functionalities present in the natural members of the resorcylic acid lactones is reported (see scheme). The use of the benzylic sulfide was efficient in providing access to both LL-Z1640-2 and L-783277 by alkylation followed by oxidative elimination or reductive cleavage, respectively.

The resorcylic acid lactones (RAL) are endowed with diverse biological activity ranging from transcription factor modulators (zearalenone and zearalenol) to HSP90 inhibitors (radicicol and pochonin D) and reversible (aigialomycin D) as well as irreversible kinase inhibitors (hypothemycin and other RAL containing a cis-enone). Our interest in broadening the diversity of this family beyond naturally occurring diversity has led us to seek a general approach that could be used to address the entire spectrum of functionalities present within this family. Herein, we present our efforts on accessing macrocycles bearing an alkane, alkene, or epoxide at the benzylic position from a common benzylic sulfide intermediate to access L-783277, LL-Z1640-2, and hypothemycin.

 

DOI: 10.1002/chem.200901373 

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