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Synthesis and Evaluation of a 2,11‐Cembranoid‐Inspired Library
Author(s) -
Welford Amanda J,
Caldwell John J.,
Liu Manjuan,
Richards Meirion,
Brown Nathan,
Lomas Cara,
Tizzard Graham J.,
Pitak Mateusz B.,
Coles Simon J.,
Eccles Suzanne A.,
Raynaud Florence I.,
Collins Ian
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201505093
Subject(s) - chemical space , combinatorial chemistry , metathesis , chemistry , ring closing metathesis , ring (chemistry) , salt metathesis reaction , stereochemistry , organic chemistry , drug discovery , biochemistry , polymerization , polymer
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 SmI 2 ‐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.