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Synthesis and Evaluation of a 2,11-Cembranoid-Inspired Library.

ABSTRACT: 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.

SUBMITTER: Welford AJ

PROVIDER: S-EPMC4869678 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Synthesis and Evaluation of a 2,11-Cembranoid-Inspired Library.

Welford Amanda J AJ Caldwell John J JJ Liu Manjuan M Richards Meirion M Brown Nathan N Lomas Cara C Tizzard Graham J GJ Pitak Mateusz B MB Coles Simon J SJ Eccles Suzanne A SA Raynaud Florence I FI Collins Ian I

Chemistry (Weinheim an der Bergstrasse, Germany) 20160301 16

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 ...[more]

PMID: 26929153

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