Synthesis and Evaluation of a 2,11‐Cembranoid‐Inspired Library

نویسندگان

  • Amanda J Welford
  • John J. Caldwell
  • Manjuan Liu
  • Meirion Richards
  • Nathan Brown
  • Cara Lomas
  • Graham J. Tizzard
  • Mateusz B. Pitak
  • Simon J. Coles
  • Suzanne A. Eccles
  • Florence I. Raynaud
  • Ian Collins
چکیده

The 2,11-cembranoid family of natural products has been used as inspiration for the synthesis of a structurally simplified, functionally diverse library of octahydroisobenzofuran-based compounds designed to augment a typical medicinal chemistry library screen. Ring-closing metathesis, lactonisation and SmI2 -mediated methods were exemplified and applied to the installation of a third ring to mimic the nine-membered ring of the 2,11-cembranoids. The library was assessed for aqueous solubility and permeability, with a chemical-space analysis performed for comparison to the family of cembranoid natural products and a sample set of a screening library. Preliminary investigations in cancer cells showed that the simpler scaffolds could recapitulate the reported anti-migratory activity of the natural products.

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عنوان ژورنال:

دوره 22  شماره 

صفحات  -

تاریخ انتشار 2016