Premium
Total Synthesis of Pectenotoxin‐2
Author(s) -
Fujiwara Kenshu,
Suzuki Yuki,
Koseki Nao,
Aki Yuichi,
Kikuchi Yuta,
Murata Shunichi,
Yamamoto Fuyuki,
Kawamura Mariko,
Norikura Toshio,
Matsue Hajime,
Murai Akio,
Katoono Ryo,
Kawai Hidetoshi,
Suzuki Takanori
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201308502
Subject(s) - anomer , chemistry , isomerization , stereochemistry , stereoselectivity , total synthesis , fkbp , sulfone , catalysis , organic chemistry , biochemistry
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.