A novel synthetic route towards anti-inflammatory mediator: Resolvin E1

The health benefits of fish oil supplementations have been proven to be effective by several studies which are discussed in this thesis. It was found that these compounds had potent anti-inflammatory properties and since then has prompted much research into the use of these compounds as potential treatments for chronic inflammation based diseases, where the overuse of current anti-inflammatory drugs cause many problems with undesired side-effects. The aim of this research is to study the bioactivity of resolvin E1 and various analogues, and to determine a novel route towards resolvin E1 natural product so that bioactivity tests may be conducted in comparison of synthetically produced resolvin E1 and naturally extracted resolvin E1. The initial aim of this research was to develop a range of analogues of a fragment of Resolvin E1. This was so that a series of compounds could be produced with various R groups to identify any structure-activity relationships for this part of the natural product. There is one stereocentre in this fragment of resolvin E1 and it was decided that a racemic version of these compounds would be tested for bioactivity, and if any of the compounds had significant anti-inflammatory properties then the R and S versions could be separated, allowing for the testing of both enantiomers to determine which gave the most potent anti-inflammatory response. This led to the creation of several novel fragments and their biological testing. The secondary aim of the project was to complete the total synthesis of the resolvin E1 natural product. We devised a novel route towards resolvin E1 which used MIDA boronate protecting group to introduce a fixed trans double bond which was useful in a compound with multiple alkene systems. Resolvin E1 also contains three stereocentres, the synthesis from the fragment work was recycled to begin the synthesis, and made use of 1,2:5,6-di-O-isopropylidene-D-mannitol and Noyori s catalyst to setup the stereocentres. The use of new MIDA-boronate moieties were also explored in order to develop a new, efficient synthesis toward resolvin E1.