Macrocyclic diarylheptanoids synthesis

The closure of macrocyclic rings represents a special field of intramolecular aryl-aryl bond formation. Irradiation of an open-chain dibromide afforded myricanone (Scheme 48) [88], which represented the first synthesis of a macrocyclic diarylheptanoid [89]. 

The total synthesis of the diarylheptanoid garugamblin 1 was achieved by M. Nogradi et al. using the modified Wurtz coupiing as the key macrocyclization step. The dibromide was treated with sodium metal at room temperature in the presence of TPE to afford the desired macrocycle in moderate yield. The N-0 bond of the isoxazole ring was cleaved under the reaction conditions. 

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