Synthesis of long chain n-3 and n-6 fatty acids having a photoactive conjugated tetraene group

Abstract

Fatty acids of the n-3 and n-6 families containing a photoactive conjugated tetraene group near the carboxylate were prepared from several naturally occurring fatty acids by sequential iodolactonization and treatment with excess 1,8-diazabicyclo[5.4.0]undec-7-ene. The new conjugated fatty acids include 5 E,7 E,9 E,11 Z,14 Z- and 5 E,7 E,9 E,11 E,14 Z-eicosapentaenoic acids derived from arachidonic acid; 5 E,7 E,9 E,11 Z,14 Z,17 Z- and 5 E,7 E,9 E,11 E,14 Z,17 Z-eicosahexaenoic acids from eicosapentaenoic acid; and 4 E,6 E,8 E,10 Z,13 Z,16 Z,19 Z- and 4 E,6 E,8 E,10 E,13 Z,16 Z,19 Z-docosaheptaenoic acids from docosahexaenoic acid. All of the newly synthesized fatty acids were characterized by UV, 1 H NMR and mass spectroscopy. These new products represent the first examples of directed conjugation of methylene interrupted double bond systems. The products can be synthesized in gram quantities and in high yields (>50%). Interestingly, it did not prove possible to synthesize fatty acids having a triene group near the carboxyl group even using mild conditions and different synthetic approaches. Once initiated, the isomerization always continued until a tetraene group was formed. Because of the sensitivity of the tetraene group to light, these fatty acids have the potential for being used in tracking fatty acid movements in cells employing fluorescence techniques and in UV light-induced cross linking to membrane proteins.