Synthetic studies toward the C5-C20 domain of the azaspiracids

An approach toward the C5-C20 THF-fused trioxadispiroketal portion of the azaspiracids is reported. The highly substituted azaspiracid D ring (C16-C19) was prepared by the one-pot conversion of a tetraol into a tetrahydrofuran. Efforts to establish the C10 and C13 spiroketal centers via an oxonium-initiated bis-spiroketalization under both kinetic and thermodynamic conditions have yielded the (10R,13S)-trioxadispiroketal 19 as the major product, which is diastereomeric with the (10R*,13R*) relative configuration assigned to the azaspiracids.