Step-efficient synthesis of marine furan fatty acids
Aim: to develop step-efficient synthetic routes to tri- and tetra-substituted furans, with the overall aim of producing furan fatty acids (FA’s) F5 and F6, alongside related fragment compounds and known metabolites such as 1 (a FA metabolite isolated from shark bile).
Heavily substituted furans are typically a challenge to synthesise, owing to the electron-rich character of the motif. The presence of one or more electron-withdrawing groups, conjugated into the ring system, is commonly needed to stabilise the compounds; FA’s F5 and F6, among many other natural products however, do not contain such substituents.
Our current work toward the synthesis of such furans involves the addition of singlet oxygen to appropriately substituted 1,3-dienes (prepared by Wittig olefination of existing enones), followed by a PPh3/CBr4 mediated reduction of the intermediate endoperoxide to give the desired furans (Scheme 1).
Novel synthetic routes towards the natural anti-Inflammatory mediator Resolvin E1
Resolvin E1 (RvE1) is a natural fatty acid produced by the body from eicosapentaenoic acid (EPA). It has been shown to reduce cellular inflammation by competing with arachidonic acid in the inflammatory response to a foreign entity. Once this fragment has been created, a series of reactions will be conducted to replace the phenyl group with other substituents and these will be tested for their anti-inflammatory properties in order to test the effectiveness of this fragment before adding it to the final structure.
The initial aim is to synthetically produce the natural product RvE1.
Currently the final fragment is being finalised using the above retrosynthetic plan.
