Regioselective synthesis of 6-substituted 2-hydroxybenzaldehyde: efficient synthesis of the immunomodulator tucaresol and related analogues

Abstract

Two new improved procedures have been developed for the preparation of the immunostimulant tucaresol 1 [4-(2-formyl-3-hydroxyphenoxymethyl)benzoic acid]. These approaches, which start from resorcinol or 2,6-dimethoxybenzaldehyde, are practical and therefore amenable to scale-up. In the case of the second approach, the multi-step synthesis reported in the literature has been reduced to three steps. Furthermore, unlike the reported method, our synthesis is versatile for the preparation of tucaresol analogues. The method is general and applicable for the preparation of 6-substituted 2-hydroxybenzaldehydes.