Picrotoxanes toxicity

Isolation from Toxic Honey and Quantitative Analysis of its Main Picrotoxanes... 

Via a plant hopper and honeybees, partly metabolized picrotoxanes from Coriaria spp. growing in New Zealand are found in toxic honey. The rather difficult isolation of picrotoxanes from honey has been described several times 2,3,10,99,100) and even now the procedure seems not entirely satisfactory (700). Originally, the isolation of picrotoxanes was achieved by extraction of honey with acetone. Later, ethyl acetate was the preferred solvent. In the late 1960s, the two main picrotoxanes were identified as tutin (11) and hyenanchin (15). Originally, the detection was governed by the physical properties of crystals obtained, color reactions, and bromoether formation. Palmer—Jones then developed a method... 

Like H. globosa the Jamaica walnut or blackwood or bitter plum (P. baccatum) contains sesquiterpenes as well as norditerpenes of the picrotoxane type. Picro-dendrin Q (74), the most toxic picrotoxane for mammals, is found in the bark of this tree. In the Dominican Republic, the tree is also called mata becerro (calf killer) and its bark is used to kill lice and bed bugs (239). 

Although Dendrobium species are much better known as ornamental plants and for their use in traditional medicine, their alkaloids, the dendrobines, are also convulsants (2). The effects of dendrobinium chloride intoxication resemble more those of strychnine intoxication than those of picrotoxinin intoxication (240). The minimal lethal dose (intravenous) in rats and mice is 20 mg/kg. The toxicity of the picrotoxanes is attributable to their ability to overcome the blood-brain barrier and to bind to inhibitory Cys-loop receptors of the postS3napses of the CNS. 

In Western medicine, picrotoxanes have played but a marginal role therapeutically. Picrotoxin was described as analeptic. Porter recorded that picrotoxin was found to be an antidote against chloral hydrate and in consequence it was used also as an antidote against barbiturate intoxication (2). It was this activity that made biomedical researchers aware of its potential as research tool in neurochemistry. Due to its high toxicity, even its use as antidote is restricted, however. Picrotoxin is employed to treat vertigo and nausea in homeopathic preparations (25i). 

Wakamatsu K, Kigoshi H, Niiyama K, Niwa H, Yamada K (1986) Stereocontrolled Total Synthesis of (+)-Tutin and (+)-Asteromurin A, Toxic Picrotoxane Sesquiterpenes. Tetrahedron 42 5551... 

Two new sesquiterpenoids of the picrotoxane group are amotin (208) and amoenin (209). In the course of an investigation of the toxic substances of the honeydew honey excreted by a sap-sucking insect which feeds on Coriaria arborea Lindsey, the two dihydro-derivatives of tutin (210) and hyenanchin (211) have been identified.Included in this paper are the n.m.r. spectral assignments of a number of compounds belonging to the picrotoxane series. Another milestone in sesquiterpenoid chemistry has been passed by the successful synthesis of (-)-picrotoxinin (212) starting from (-)-carvone (Scheme 33).One of the crucial steps in this fairly long synthesis was the double lactonization towards the end of the route. 

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