Convenient approach for the synthesis of ONO-LB-457, a potent leukotriene B4 receptor antagonist

This study reports a new approach for the synthesis of 5-[2-(2-carboxyethyl)-3-[6-(4-methoxyphenyl)-(5E)-hexen-1-yloxy]phenoxy]pentanoic acid V (ONO-LB-457), previously described by Konno and col. which is considered highly potent orally active LTB4 receptor antagonist. compound acts as an inhibitor aggregation chemotaxis, in addition to LTB4-induced human neutrophil degranulation. In this work, preparation ONO-LB-457 was proposed through convergent focused on two fragments. First, 5-hydroxychroman-2-one (4) from 2,6-dimethoxybenzaldehyde malonic acid, involving Knoevenagel reaction, followed reduction olefin intramolecular cyclization catalyzed Lewis (tribromide) achieved with overall yield 57%. Second, (E)-6-(4-methoxyphenyl)hex-5-en-1-yl-methanesulfonate (18) 5-bromovaleric (15) Wittig reaction. The desired (ONO-LB-457) obtained nucleophilic substitution ring-opened phenolic diester 14 hydrolysis, seven steps about 11%.