Unit:
Κατεύθυνση Οργανική Σύνθεση και Εφαρμογές της στη Χημική ΒιομηχανίαLibrary of the School of Science
Supervisors info:
Γεώργιος Κόκοτος, Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Δημήτριος Γεωργιάδης, Αναπληρωτής Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Χριστόφορος Κόκοτος, Επίκουρος Καθηγητής, Τμήμα Χημείας,Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
Ασύμμετρη σύνθεση κορεσμένων υδρόξυ λιπαρών οξέων και εστέρων τους με λιπαρά οξέα
Translated title:
Asymmetric synthesis of saturated hydroxy fatty acids and their esters with fatty acids
Summary:
Lipidomic analysis of the adipose tissue of mice genetically engineered to overexpress the glucose transporter Glut4 (AG4OX mice) led to the discovery of a new class of endogenous lipids called Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs), which are composed of two acyl chains linked through an ester linkage.
Identification of FAHFAs showed that there is a correlation between the structure and the activity they appear to exhibit. More specifically, the esters present both a regio isomerization concerning the position of the hydroxyl group forming the ester bond as well as an enantiomerization since the organism itself chooses to hydrolyze between the (R) and (S) enantiomers, the latter, while the (R) isomer stimulates mechanisms that impart anti-diabetic and/or anti-inflammatory activity to this class of compounds.
This thesis constitutes a general methodology for the asymmetric synthesis of FAHFAs and their corresponding hydroxy acids from which they are derived. Until now, the only published enantiopure FAHFA synthesis starts from chiral starting material. The synthetic route we developed involves the introduction of chirality through a key-step, with the formation of an asymmetric terminal epoxide using a MacMillan imidazolidinone as a catalyst. At the same time, it allows the introduction of a double bond leading to unsaturated fatty esters.
Finally, the synthesis of deuterated hydroxy acids and FAHFAs is important, as such derivatives can be used both to understand their biosynthesis and degradation mechanisms and as reference compounds in high resolution mass spectometric studies (HRMS).
Main subject category:
Science
Keywords:
FAHFAs, hydroxy acids, asymmetric synthesis, deuteration, organocatalysis
