Abstract

Syntheses of a crystalline polycyclic halichondrin C1-C14 building block starting from a d-gulono-1,4-lactone-derived intermediate in the current Halaven manufacturing process are described. Key features of the syntheses include an acid-catalyzed tandem intermolecular oxy-Michael/intramolecular trans-ketalization reaction and stereoselective Kishi reductions.

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