Stereocontrolled synthesis of 8,11-dideoxytetrodotoxin, an unnatural analogue of puffer fish toxin.
8,11-Dideoxytetrodotoxin, an unnatural tetrodotoxin analogue, was synthesized in a highly stereoselective manner from a common intermediate from our synthetic studies on tetrodotoxin. The key features in the synthesis were as follows: neighboring group participation of a trichloroacetamide to allow regioselective and stereoselective hydroxylation, protection of a delta-hydroxylactone as an ortho ester, and guanidine installation through the use of Boc-protected isothiourea. Global deprotection of the fully protected intermediate under acidic conditions gave 8,11-dideoxytetrodotoxin, which exhibited very weak biological activities.
Nishikawa
Toshio
T
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Urabe
Daisuke
D
Yoshida
Kazumasa
K
Iwabuchi
Tomoko
T
Asai
Masanori
M
Isobe
Minoru
M
D000818:Animals; D008968:Molecular Conformation; D013237:Stereoisomerism; D023721:Tetraodontiformes; D013779:Tetrodotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
C465250:8,11-dideoxytetrodotoxin; D013779:Tetrodotoxin