Total Synthesis of Spirastrellolide A Methyl Ester—Part 1: Synthesis of an Advanced C17–C40 Bis-spiroacetal Subunit


  • This work was supported by the EPSRC (GR/C541677/1), Merck Research Laboratories, Homerton College, Cambridge (E.A.A.), SK Corporation (J.H.L.), and the German Academic Exchange Service (C.M.). We thank Prof. R. J. Andersen (University of British Columbia) for helpful discussions.


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Out of the blue: The marine macrolide spirastrellolide A is a potent and selective inhibitor of protein phosphatase 2A and a lead for anticancer therapies. A flexible and modular synthetic strategy has been developed with two routes for the construction of the DEF bis-spiroacetal subunit. The optimized Suzuki coupling approach results in the efficient preparation of a C17–C40 aldehyde that forms the cornerstone of the first total synthesis.