Clickable Lipids: Azido and Alkynyl Fatty Acids and Triacylglycerols

Hydroxy fatty acids (FAs), which were isolated from glycolipids that can be prepared fermentatively from fats and oils, have been synthetically modified to contain azide and alkyne functional groups. These particular functional groups were chosen because they can participate in a copper-catalyzed reaction that combines them to form a 1,4-triazole, known as a “click” reaction, which has been widely used in a variety of fields but remains underutilized in FA chemistry. Depending on the starting hydroxy FA, these groups can be close to the carboxy unit (using 3-hydroxydecanoate) and hence the polar glycerol group, or distant from it (using 17-hydroxyoctadecanoate). These structural alternatives will impart different properties to the triacylglycerols that are subsequently prepared from the modified FA. Finally, the click reaction was used to conjugate triacylglycerols to each other and to other molecules such as a glycolipid or a protected amine.