Stereoselective Construction of a Contiguous Tetraol System in Tetrodotoxin by Means of Repetitive Operations Involving Epoxidation and Ring-opening Reactions of Allyl Sulfone

Stereoselective construction of a tetraol system corresponding to C-5, 6, 7, and 11 in tetrodotoxin was achieved. Epoxidation of allyl sulfide 3 followed by base-induced ring-opening reaction gave hydroxyallyl sulfone 6. Repetition of the above reactions gave 1,3-dihydroxyvinyl sulfone 8, which was transformed to protected tetraols 18 and 20 by a series of sequential reactions: 1) reductive removal of the phenylsulfonyl group, 2) inversion of the α-axial TBSoxy group to an β-equatorial position, and 3) dihydroxylation with Oso 4 .