title: Total synthesis of pectenotoxin-2.
abstract: Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2≫PTX2b>PTX2c.
authors.affiliation: Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810 (Japan). fjwkn@sci.hokudai.ac.jp.
authors.forename: Kenshu
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Yuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Nao
authors.initials: N
authors.lastname: Koseki
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Aki
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Murata
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Yamamoto
authors.forename: Mariko
authors.initials: M
authors.lastname: Kawamura
authors.forename: Toshio
authors.initials: T
authors.lastname: Norikura
authors.forename: Hajime
authors.initials: H
authors.lastname: Matsue
authors.forename: Akio
authors.initials: A
authors.lastname: Murai
authors.forename: Ryo
authors.initials: R
authors.lastname: Katoono
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kawai
authors.forename: Takanori
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000080:Acetals / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D003500:Cyclization; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D056945:Hep G2 Cells; D006801:Humans; D007536:Isomerism; D018942:Macrolides; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013141:Spiro Compounds / Q000737:chemistry; D000095702:Polyether Toxins
chemical_list: D000080:Acetals; D005663:Furans; D018942:Macrolides; D011714:Pyrans; D013141:Spiro Compounds; C098380:pectenotoxin 2; D000095702:Polyether Toxins
keywords: isomerization; macrocycles; natural products; spiro compounds; total synthesis