Synthesis of hydroxy-γ-sanshool

Hydroxy-γ-sanshool was prepared with 19.5% overall yield through eight steps. Wittig reactions of ylides with ethyl 4-oxobut-2-enoate as well as (2E,4E)-hex-2,4-dienal were key steps to construct a carbon skeleton. The 2E,4Z-isomer in ethyl 8-hydroxyocta-2,4-dienoate can be isomerized to the desired 2E,4E-isomer with iodine as a catalyst, and free tetradeca-2,4,8,10,12-pentaenoic acid can be purified through crystallization in 1% ethyl acetate in n-hexane. The impurities in other intermediates can be easily removed, the synthetic process can avoid the synthesis or use of 4-bromobutyraldehyde which comes from the oxidation of unstable 4-bromobutan-1-ol, and the work-ups were simple. Graphic abstract: