Abstract
3-Hydroxy fatty acids have attracted the interest of researchers, since some of them may interact with free fatty acid receptors more effectively than their non-hydroxylated counterparts and their determination in plasma provides diagnostic information regarding mitochondrial deficiency. We present here the development of a convenient and general methodology for the asymmetric synthesis of 3-hydroxy fatty acids. The enantioselective organocatalytic synthesis of terminal epoxides, starting from long chain aldehydes, is the key-step of our methodology, followed by ring opening with vinylmagnesium bromide. Ozonolysis and subsequent oxidation leads to the target products. MacMillan’s third generation imidazolidinone organocatalyst has been employed for the epoxide formation, ensuring products in high enantiomeric purity. Furthermore, a route for the incorporation of deuterium on the carbon atom carrying the hydroxy group was developed allowing the synthesis of deuterated derivatives, which may be useful in biological studies and in mass spectrometry studies. In addition, the synthesis of fatty γ-lactones, corresponding to 4-hydroxy fatty acids, was also explored.
Highlights
Saturated and unsaturated fatty acids (FAs), as well as hydroxy fatty acids (HFAs) are components of biomolecules and have been shown to exert cellular effects through G protein–coupled receptors named free fatty acid receptors (FFA1–FFA4) and hydroxycarboxylic acid receptors (HCA1–HCA3) [1].A recent study has shown that the G protein-coupled receptor 84 (GPR84) is activated by 2-hydroxy or3-hydroxy medium chain fatty acids more effectively than by their non-hydroxylated counterparts [2].3-Hydroxy fatty acids are produced in mitochondria by β-oxidation [3] and are constituents of inflammatory lipopolysaccharides [4]
Organocatalysis has been recognized as a powerful methodology in asymmetric catalysis, Organocatalysis has beenand recognized asand a powerful methodology in for asymmetric catalysis, complementing metal catalysis biocatalysis offering new opportunities the enantioselective complementing metal catalysis and biocatalysis and offering new opportunities synthesis of biomolecules [14]
The organocatalytic formation of epoxides was selectedfor as the the enantioselective synthesis of biomolecules
Summary
Saturated and unsaturated fatty acids (FAs), as well as hydroxy fatty acids (HFAs) are components of biomolecules and have been shown to exert cellular effects through G protein–coupled receptors named free fatty acid receptors (FFA1–FFA4) and hydroxycarboxylic acid receptors (HCA1–HCA3) [1].A recent study has shown that the G protein-coupled receptor 84 (GPR84) is activated by 2-hydroxy or3-hydroxy medium chain fatty acids more effectively than by their non-hydroxylated counterparts [2].3-Hydroxy fatty acids are produced in mitochondria by β-oxidation [3] and are constituents of inflammatory lipopolysaccharides [4]. A recent study has shown that the G protein-coupled receptor 84 (GPR84) is activated by 2-hydroxy or. 3-hydroxy medium chain fatty acids more effectively than by their non-hydroxylated counterparts [2]. The determination of 3-hydroxy fatty acids in plasma or tissue cultures provides diagnostic information regarding medium/short-chain mitochondrial L-3 hydroxyacyl coenzyme A dehydrogenases (M/SCHAD) deficiency [5]. A method for the quantitative profiling of 3-hydroxy fatty acids as environmental markers of endotoxin in occupational and environmental samples has been developed, using liquid chromatography coupled to tandem mass spectrometry [6]. Several methods for the synthesis of 3-hydroxy acids are known in the literature.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
