Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
Org Biomol Chem. 2023 Oct 25;21(41):8294-8300. doi: 10.1039/d3ob01076g.
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 A (LXA) have been well studied, analogues of lipoxin B (LXB) have been the focus of considerably less attention. Herein we report the asymmetric synthesis of a focused library of LXB 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.
脂氧素是一类重要的促炎消退介质，在炎症消退中发挥着关键作用。因此，合成更具化学和代谢稳定性的合成脂氧素类似物是一个非常关注的领域。虽然脂氧素 A（LXA）的合成类似物已经得到了很好的研究，但脂氧素 B（LXB）的类似物受到的关注要少得多。在这里，我们报告了脂氧素 B 类似物的不对称合成，其中该分子的三烯核心已被不同的芳环和杂芳环取代。这些类似物的合成均采用了一种通用策略，其中关键步骤是常见的上链片段与芳族下链之间的 Suzuki 交叉偶联，然后进行立体选择性酮还原。
