title: Total Synthesis of (-)-Histrionicotoxin through a Stereoselective Radical Translocation-Cyclization Reaction.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Sato
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Azuma
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Daigaku
authors.affiliation: ERATO, Isobe Degenerate π-Integration Project and Advanced Institute for Materials Research (AIMR), 2-1-1 Katahira, Aoba-ku, Sendai, 980-8577, Japan.|AIMR and Department of Chemistry, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Sota
authors.initials: S
authors.lastname: Sato
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Kiyosei
authors.initials: K
authors.lastname: Takasu
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Okano
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tokuyama
mesh_terms: D000080:Acetals / Q000737:chemistry; D000664:Amphibian Venoms / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D000080:Acetals; D000664:Amphibian Venoms; D005609:Free Radicals; C007948:histrionicotoxin
keywords: alkaloids; diastereoselectivity; radical cyclization; spiro compounds; total synthesis