Abstract: Natural product erythro-(-)-(1R,2S)-Myrislignan, which was firstly found in the seeds of nutmeg of the aril(mace) of Myristica fragrans Houtt(Myristicaceae) used as traditional Chinese medicine in China and Japan and it has attracted increasing interest because of its biological activities, was synthesized for the first time in high yields from vanillin. The synthesis was based on a unified synthetic strategy and involved Wittig reaction, LiAlH₄ reduction and Sharplass asymmetric dihydroxylation reaction to prepare a threo-intermediate of predictable stereochemistry. Then pyrogallic acid was employed as material to prepare the other phenylpropanoid unit by Claisen rearrangement reaction. The stereoselective coupling between the threo-intermediate and phenylpropanoid unit inverted the absolute configuration from threo- to erythro-isomer using the Mitsunobu reaction to give the target product. The route illustrates a new methodology for the synthesis of erythro-8-O-4′ neolignans.

Key words: Asymmetric synthesis, Myrislignan, Neolignan, Mitsunobu reaction