Chemoenzymatic Approach to Tetrodotoxin: Synthesis of Fukuyama’s, Alonso’s, and Sato’s Advanced Intermediates

The advanced intermediates in the syntheses of tetrodotoxin reported by Fukuyama, Alonso, and Sato were prepared. The key steps in the synthesis of the title compounds involved the toluene dioxygenase–mediated dihydroxylation of either iodobenzene or benzyl acetate. The resulting diene diols were transformed to Fukuyama’s intermediate in six steps, to Alonso’s intermediate in nine steps and to Sato’s intermediate in ten steps, respectively.NSERC Idea to Innovation - I2IPJ-470630-14 NSERC Discovery Grant - RGPIN-2018-0372