A general synthesis of aromatic and heteroaromatic lipoxin B4 analogues

Abstract

Lipoxins are an important class of pro-resolving mediators that play a crucial role in the resolution of inflammation. Thus, the synthesis of more chemically and metabolically stable synthetic lipoxin analogues is an area of significant interest. Whereas synthetic analogues of lipoxin A₄ (LXA₄) have been well studied, analogues of lipoxin B₄ (LXB₄) have been the focus of considerably less attention. Herein we report the asymmetric synthesis of a focused library of LXB₄ mimetics in which the triene core of the molecule has been replaced with different aromatic and heteroaromatic rings. The synthesis of each of these analogues was achieved by a general strategy in which the key steps were a Suzuki cross coupling between a common upper chain fragment and an aromatic lower chain, followed by a stereoselective ketone reduction.