Tetra- and penta-vicinally fluorinated cyclohexane ring motifs
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Date
26/06/2019Author
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Abstract
Organofluorine compounds have had an important influence on the advances in the
healthcare and agricultural industries. Selective substitution with fluorine can produce a
significant impact on the pharmacokinetic properties of bioactive compounds; generally this
is through stereoelectronic effects that the fluorine atom can confer. As such, there is a
continuous interest in the development of novel organofluorine compounds and the
incorporation of fluorine into bioactive compounds and natural products.
The all-cis-1,2,4,5-tetrafluorocyclohexane motifs were the first examples of facially polarised
cyclohexane rings which possess a dipolar nature arising from two 1,3-diaxial C-F bonds. The
fluorine face, which possesses a negative electrostatic profile, along with the positively
polarized methylene hydrogens on the opposite face give a unique facial polarity to this
motif.
These highly polarized fluorinated ring systems present as novel building blocks for use in
drug development and agricultural programs; hence the aim of this study was the
development of functionalised derivatives of these all-cis tetrafluoro-cyclohexanes.
Transformations of previously reported phenyl all-cis-2, 3, 5, 6-tetrafluoro-cyclohexane were
explored in a variety of directions and new pathways towards partially fluorinated
cyclohexanes were investigated. The range of all-cis-tetrafluorocyclohexane motifs
produced, with functional groups attached directly to the fluorinated cyclohexane ring,
varied from methyl substituted all-cis-tetrafluorocyclohexane alcohols, aldehydes, nitriles
and amines to all-cis-tetrafluorocyclohexane amino acid, pentafluoro carboxylic acid and
alcohol derivatives.
These novel derivatives were then used in liquid-phase peptide synthesis, incorporated into
peptidomimetic systems through Ugi multi-component reactions and utilised in the
formation of bis-systems, in order to demonstrate their reactivity and to gain an insight into
their possible intramolecular conformational preferences and supramolecular
arrangements.
Type
Thesis, PhD Doctor of Philosophy
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