Conformations of 3-carboxylic esters essential for neurotoxicity in veratrum alkaloids are loosely restricted and fluctuate.
The lipid-soluble veratrum alkaloids, veratridine and cevadine, are plant neurotoxins that are agonists of voltage-gated sodium channel. Their conformations in a hydrophobic environment were analyzed by NMR spectroscopy in solution phase chloroform at low temperatures. The conformations around the 3-carboxylic esters which is essential for their neurotoxicity, was completely different from the previously reported X-ray crystallographic structure. The carbonyl oxygen atom (O28) of the carboxylic ester forms a weak intramolecular hydrogen bond with the OH proton at C4 (4-OH) that loosely restricts the conformation of the 3-veratroyl ester in veratridine and the 3-angeloyl ester in cevadine. Methylation at C4 hydroxyl group of veratridine had much reduced its neurotoxic activity relating to voltage-gated sodium channel. The results suggested that the loose conformational restrictions of the carboxylic esters are important for neurotoxicity of the veratrum alkaloids.
Niitsu
Ai
A
Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
Harada
Masanori
M
Yamagaki
Tohru
T
Tachibana
Kazuo
K
D002725:Chloroform; D003080:Cold Temperature; D004952:Esters; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009498:Neurotoxins / Q000737:chemistry; D062687:Sodium Channel Agonists; D014701:Veratridine / Q000737:chemistry; D014702:Veratrine / Q000737:chemistry; D014704:Veratrum Alkaloids / Q000737:chemistry*
D004952:Esters; D009498:Neurotoxins; D062687:Sodium Channel Agonists; D014704:Veratrum Alkaloids; D014701:Veratridine; D002725:Chloroform; D014702:Veratrine