1225609-72-2Relevant academic research and scientific papers
Synthesis of reblastatin, autolytimycin, and non-benzoquinone analogues: Potent inhibitors of heat shock protein 90
Wrona, Iwona E.,Gozman, Alexander,Taldone, Tony,Chiosis, Gabriela,Panek, James S.
supporting information; experimental part, p. 2820 - 2835 (2010/08/05)
A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (～25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (～100 nM).
