Synthesis of fluoro analogues of unsaturated fatty acids and corresponding acyclic metabolites

Abstract

Polyunsaturated fatty acids, in particular arachidonic acid and its metabolites, the so-called eicosanoids, play a major role in human health. Many of them have been involved as potent mediators for various diseases such as inflammation and asthma. Therefore, numerous modifications in the structures of these natural products have been incorporated to study the structure-activity relationship, monitor the biosynthetic pathway and also to understand the biological activities as well as the mechanisms of action. The modifications include introduction of labelled elements, fluorine atoms, heteroelements, carbo- and heterocycles etc. Of all these studies, the introduction of fluorine, which has a unique role as the smallest atom in the periodic table after hydrogen and also as the most electronegative element, provided very useful information. Thus, the present microreview highlights the synthetic efforts of various research groups in the last two decades on bioactive fluorinated fatty acids and corresponding acyclic metabolites. It also presents the most relevant bioactivity data obtained from the fluorinated analogues. The data corresponding to naturally occurring fluorinated fatty acids have been added, as well as the use of fluorinated probes for some biosynthetic studies in fatty acid chemistry (desaturation and methylenation). In addition, it is important to point out that the methods and strategies which have been developed to selectively introduce a single fluorine atom, as well as CF2 or CF3 groups, on such very challenging molecules could also be of much use in many other areas of chemistry. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).