Synthesis and evaluation of derrubone and select analogues

[GRAPHICS] Recently, we reported that the natural product derrubone exhibits Hsp90 inhibitory activity. Due to its unique architectural scaffold and proposed rapid assembly, the synthesis of this natural product was pursued with the aim of identifying structure-activity relationships. Synthesis of the natural product was accomplished in eight highly convergent steps, which led to a facile method for the construction of related compounds. Biological evaluation of derrubone and its analogues identified several compounds that exhibit low micromolar inhibitory activity against breast and colon cancer cell lines.