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

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.