Synthesis of the ABC Framework of Tamulamides A and B

Bioorganic & Medicinal Chemistry 26(19), 5327-5335, DOI: 10.1016/j.bmc.2018.04.046

Synthesis of the fused tetrahydrofuran motif comprising the ABC rings of the marine ladder polyethers tamulamides A and B has been achieved via two different polyepoxide cascade strategies. Investigations into a triepoxide cascade under aqueous conditions revealed the importance of the electronic nature of the cascade end-group with this initial approach. Ultimately, a diepoxide cascade under basic conditions proved most successful, providing the ABC tetrahydropyran triad in 41% yield.