Mears, Paul R, Hoekman, Steven, Rye, Claire E, Bailey, Fiona P, Byrne, Dominic P, Eyers, Patrick A ORCID: 0000-0002-9220-2966 and Thomas, Eric J
(2019)
Towards 20,20-difluorinated bryostatin: synthesis and biological evaluation of C17,C27-fragments.
ORGANIC & BIOMOLECULAR CHEMISTRY, 17 (6).
pp. 1487-1505.
Text
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Abstract
Bryostatins with modified C17-C27 fragments have not been widely studied. The synthesis of 20,20-difluorinated analogues was therefore investigated. Such substitution would inhibit dehydration involving the C19-hydroxyl group and stabilise the ring-closed hemiacetal tautomers. Following preliminary studies, allyldifluorination was used to prepare difluorinated alkenols. Oxidation followed by stereoselective Wittig reactions of the resulting α,α-difluorinated ketones gave (E)-α,β-unsaturated esters that were taken through to complete syntheses of 2-hydroxytetrahydropyrans corresponding to C17-C27 fragments of 20,20-difluorinated bryostatin. These compounds showed modest binding to protein kinase Cα isozyme. Attempts were also undertaken to synthesise macrocyclic 20,20-difluorinated analogues. During preliminary studies, allyldifluorination was carried out using a 2-alkyl-3-bromo-1,1-difluoropropene.
Item Type: | Article |
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Uncontrolled Keywords: | Protein Kinase C, Molecular Conformation, Models, Molecular, Bryostatins, Halogenation, Chemistry Techniques, Synthetic |
Depositing User: | Symplectic Admin |
Date Deposited: | 28 Jan 2020 09:10 |
Last Modified: | 19 Jan 2023 00:08 |
DOI: | 10.1039/c8ob03152e |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3072150 |