Total Synthesis of (-)-Histrionicotoxin through a Stereoselective Radical Translocation-Cyclization Reaction.

Stereoselective total syntheses of (-)-histrionicotoxin and (-)-histrionicotoxin 235A are described. The 1-azaspiro[5.5]undecane skeleton was constructed diastereoselectively by a radical translocation-cyclization reaction involving a chiral cyclic acetal; the use of tris(trimethylsilyl)silane was crucial for the high diastereoselectivity. The cyclization product was converted into (-)-histrionicotoxin 235A through a one-pot partial-reduction-allylation reaction of a derivative containing an unprotected lactam. Finally, two terminal alkenes were transformed into enynes with the 1,3-amino alcohol protected as an oxathiazolidine oxide to complete the total synthesis of (-)-histrionicotoxin.