ABSTRACT
The structure of iso-grayanotoxin II, a new diterpenoid from Leucothoe grayana MAX., has been determined as 3 beta,5 beta,6 beta,14 beta,16 alpha-pentahydroxygrayanotox-9(10)-ene by spectroscopic and X-ray crystallographic analysis. The lethal dosage level of iso-grayanotoxin II in mice was lower than that of grayanotoxin III.
Subject(s)
Diterpenes/chemistry , Diterpenes/toxicity , Plant Leaves/chemistry , Plants, Toxic/chemistry , Toxins, Biological/chemistry , Toxins, Biological/toxicity , Animals , Chromatography, Gas , Crystallography, X-Ray , Diterpenes/isolation & purification , Isomerism , Male , Mice , Mice, Inbred ICR , Molecular Conformation , Spectrophotometry, Infrared , Toxins, Biological/isolation & purificationABSTRACT
Grayanotoxin (GTX) III, a tetracyclic diterpenoid, is the main toxic component obtained from the leaves of Leucothoe grayana MAX. In this paper, we report the correlation between toxicity and C10 stereostructure of GTX-III. 10-epi-GTX-III was derived from GTX-III in four steps. Oxidation of the GTX-II-3,6,14,16-tetraacetate with formic acid/hydrogen peroxide in chloroform gave 10,20-epoxy derivation in high yield. Reduction of the 10,20-epoxyacetate with LiAlH4 in tetrahydrofuran gave the two products, 10-epi-GTX-III and 10,20-epoxy-GTX-II. The absolute structure of the 10-epi-GTX-III was deduced from the results of X-ray crystallographic analysis. Dosage level of acute toxicity of 10-epi-GTX-III in mice was estimated at about half of natural GTX-III.
Subject(s)
Diterpenes/chemistry , Plants, Toxic/chemistry , Toxins, Biological/chemistry , Animals , Crystallography, X-Ray , Diterpenes/toxicity , Mice , Mice, Inbred ICR , Molecular Conformation , Toxins, Biological/toxicityABSTRACT
Dialkyldithiocarbamates injected into mice 0.5 h prior to alloxan protected dose-dependently against the diabetogenic action of alloxan, and increased blood glucose levels at the time of alloxan injection. Furthermore, they exhibited anti-oxidative properties in vitro such as inhibition of lipid peroxidation, removal of hydrogen peroxide and reduction of the stable free radical, 1, 1-diphenyl-2-picrylhydrazyl (DPPH). These results suggest that dialkyldithiocarbamates protect against the development of alloxan-induced diabetes by the indirect mechanism of producing hyperglycemia at the time of alloxan injection and possibly by their anti-oxidative effects as well.
