Synthetic Studies towards Streptoseomycin

Streptoseomycin belongs to the nargenicin family of macrolides with potent antibacterial activity. Due to the complex molecular structure, total synthesis of streptoseomycin has not been reported. Herein, our efforts on construction of the tricyclic core featuring ether-bridge across the cis-decalin with all requisite functionalities for streptoseomycin are reported. The key synthetic strategy relies on Diels-Alder reaction of benzoquinone with Danishefsky diene, intramolecular Michael addition, and intramolecular SN2 etherification. Our successful construction of this tricyclic core not only uncovered many unexpected transformations but also laid a solid ground for the total synthesis of streptoseomycin.