Lipoxins are a group of bioactive compounds enzymatically derived from arachidonic acid by a family of lipoxygenase enzymes, which were first isolated from human leukocytes by Serhan and Samuelsson in 1984.[1] The two naturally occurring Lipoxins, Lipoxin A4 (LXA4) (1) and Lipoxin B4 (LXB4) (2) are trihydroxytetraene-containing eicosanoids. Lipoxins regulate components of both the innate and adaptive immune systems to initiate the resolution of inflammation by activating the FPR2/ALX receptor.[2,3] Although a healthy bodily response, the effective resolution of inflammation is essential to maintain normal tissue homeostasis and the prevention of chronic inflammatory diseases. The major obstacle associated with using Lipoxins to treat diseases caused by chronic inflammation is the rapid metabolism observed in vivo, which is characteristic of all autacoids. These LX metabolites exhibit dramatically decreased biological activity and are considered inactive metabolites, rendering them poor potential pharmacological agents.[4] Within our research group the rapid metabolic inactivation has been overcome by synthesising aromatic and heteroaromatic analogues of LXA4 increasing the potency over 1,000 fold.[5] The focus of this project is to synthesise a wide range of LXA4 analogues specifically designed to overcome the rapid metabolic deactivation, in particular the β-oxidation of the upper chain of which is known to be another source of metabolic instability in LXA4. The research involves both advanced asymmetric synthesis and biological assays on THP-1 LUCIA monocyte cells.

Asymmetric synthesis of aromatic lipoxin A4 analogues with upper chain modifications

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.