Convergent total synthesis of (±) myricanol, a cyclic natural diarylheptanoid

Myricanol 1, a constituent of Myrica species, has been reported to lower the levels of the microtubuleassociated protein tau (MAPT), whose accumulation plays an important role in some neurodegenerative diseases, such as Alzheimer’s disease (AD). Herein we described a new synthetic route to prepare myricanol in 9 steps and 4.9% overall yield starting from commercially available 2,3-dimethoxyphenol and methyl 3-(4-benzyloxyphenyl)propanoate. The key steps are a cross-metathesis to obtain a linear diarylheptanoid intermediate and a Suzuki–Miyaura domino reaction to generate the challenging macrocycle.