Synthesis of a Bicyclo[1.1.1]pentane‐Containing Aromatic Lipoxin B4 Analogue and Heteroaromatic Congeners

Lipoxins are pro-resolving mediators that play an important role in the resolution phase of the innate inflammatory response. However, because of their chemical and metabolic instability, the design of more stable synthetic analogues of lipoxin A4 and lipoxin B4 is an ongoing area of study.  Herein we report the asymmetric synthesis of an aromatic lipoxin B4 analogue containing a conformationally rigid and potentially more metabolically resistant bicyclo[1.1.1]pentane (BCP) ring incorporated into the upper alkyl chain. This was achieved by the development of a 9-step chiral-pool synthesis of a novel BCP-containing boronic ester coupling partner which could serve as a common precursor to the target analogue as well as other analogues with further modifications to the aromatic core.