Novel phenoxazine dyes : laccase-mediated synthesis, physico-chemical properties and applications
(2010)
Files
TheseFBruyneel.pdf
Open Access - Adobe PDF
- 3.32 MB
Details
- Authors
- Supervisors
- Marchand-Brynaert, Jacqueline
- Abstract
- (en) Laccases are members of the multicopper oxidase family which are involved in numerous biosynthetic pathways in fungi. Among these, one laccase has been shown to produce in vitro a natural pigment, namely the cinnabarinic acid, which is related to the actinomycin chromophore. The core structure of this chromophore, i.e 2-amino-3H-phenoxazin-3-one, was found to possess a marked potential for the fluorescent labelling in the field of molecular biology. As water-solubility is one of the critical features for biological application, efficient and original synthetic routes are needed to provide new hydrophilic fluorophores inspired from natural pigments. In the frame of the European research project SOPHIED, we have investigated the biomimetic synthesis of novel aminophenoxazinone dyes featuring tuneable water-solubility. Our synthetic route involves a key step of biocatalysed oxidative cascade with a total of 6e- oxidation mediated by a laccase. Sulfonylated and phosphorylated aminophenol building-blocks were synthesised with a total regioselectivity control and further processed as water-soluble substrates by our biocatalyst to afford novel fluorophores. The investigation of the scope and limitations of our biocatalytic process led to a new mechanistic proposal for the key step of oxidative cyclisation initiated by the laccase. Fluorescent properties of these heterocyclic scaffolds were evaluated and further assayed in a live-cell imaging application. This results in the discovery of a promising fluorophore, presumably a bulk endocytic tracer with targeting by default to lysosomes. Lastly the serendipitous discovery of an intramolecular cyclisation due to a neighbouring substituent effect of the acidic group (SO3H and PO(OH)2) in our aminophenol derivatives led to the development of an alternative synthetic route towards novel benzoxazole derivatives of potential interest in medicinal chemistry.
- Affiliations
Citations
Bruyneel, F. (2010). Novel phenoxazine dyes : laccase-mediated synthesis, physico-chemical properties and applications. https://hdl.handle.net/2078.5/129505