Synthesis and Evaluation of a 2,11-Cembranoid-Inspired Library.
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Authors
Welford, AJ
Caldwell, JJ
Liu, M
Richards, M
Brown, N
Lomas, C
Tizzard, GJ
Pitak, MB
Coles, SJ
Eccles, SA
Raynaud, FI
Collins, I
Caldwell, JJ
Liu, M
Richards, M
Brown, N
Lomas, C
Tizzard, GJ
Pitak, MB
Coles, SJ
Eccles, SA
Raynaud, FI
Collins, I
Document Type
Journal Article
Date
2016-04-11
Date Accepted
2016-04-01
Date Available
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.
Citation
Chemistry (Weinheim an der Bergstrasse, Germany), 2016, 22 (16), pp. 5657 - 5664
Source Title
Publisher
WILEY-V C H VERLAG GMBH
ISSN
0947-6539
eISSN
1521-3765
Collections
Research Team
Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
Medicinal Chemistry 1
Medicinal Chemistry 2
Medicinal Chemistry 4 (including Analytical Chemistry)
Tumour Biology & Metastasis
Medicinal Chemistry 1
Medicinal Chemistry 2
Medicinal Chemistry 4 (including Analytical Chemistry)
Tumour Biology & Metastasis