Total synthesis of ciguatoxin and 51-hydroxyCTX3C.
Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are large ladder-like polycyclic ethers with the 13 ether rings ranging from five- to nine-membered. In this paper, we describe the total synthesis of the two most toxic members of the ciguatoxin family, ciguatoxin 1 and 51-hydroxyCTX3C 2, based on a unified synthetic strategy. The key features in our syntheses were (i) direct construction of the O,S-acetal from the corresponding left and right wing fragments (3, 4, 14); (ii) stereo- and chemoselective radical reaction of the alpha-oxyradical with pentafluorophenyl acrylate to achieve cyclization of the seven-membered G-ring; (iii) ring-closing metathesis reaction to build the nine-membered F-ring; and (iv) an efficient protective group strategy using the oxidatively removable 2-naphthylmethyl groups.
Inoue
Masayuki
M
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan. inoue@ykbsc.chem.tohoku.ac.jp
Miyazaki
Keisuke
K
Ishihara
Yuuki
Y
Tatami
Atsushi
A
Ohnuma
Yuyu
Y
Kawada
Yuuya
Y
Komano
Kazuo
K
Yamashita
Shuji
S
Lee
Nayoung
N
Hirama
Masahiro
M
D002922:Ciguatoxins / Q000138:chemical synthesis*; D015394:Molecular Structure
C466859:51-hydroxyciguatoxin 3C; D002922:Ciguatoxins