Picrotoxane

Aduncin, a picrotoxane sesquiterpenoid isolated from Dendrobium aduncum, has been assigned structure (147) on the basis of its spectroscopic properties and their similarity to those of a- and /3-dihydropicrotoxinin (148). A full paper dealing with the previously reported synthesis of 4-epidendrobine (149) has been published (cf. Vol. 7, p. 74). 

In ref. 66 and previous reports (Vol. 7, p. 74) this compound is described as 8-epidendrobine. In this report we have adopted the generally accepted numbering system for the picrotoxane framework. It should also be noted that 4-epidendrobine does not occur in nature. 

The cyclization is quite general. The 1,6-enyne system of alkynyl /V-acylenamine 332 undergoes a similar ene-type cyclization using BBEDA (5%) to give 333 [137]. The bicyclic picrotoxane skeleton 335 has been constructed by this Pd-catalysed ene-type cyclization of 334. The cyclized product 335 was obtained in a satisfactory yield (70%) only by the combined use of the phosphine ligands 336 and 337 [138]. 

The picrotoxane sesquiterpenes are a family of natural products from a poisonous berry Menispermum cocculus which were documented as early as the 1600s by Indian natives who used them to stun fish and kill body lice. Trost and coworkers reported an approach to total synthesis of this family based on Pd-catalyzed cycloisomerization [68, 69]. Several synthesis recipes were tested and it was found that a combination of dbpp with a ligand capable of internal proton delivery (dpba) gave the best result and provided a key intermediate 27 for total syntheses of corianin, picrotoxinin, picrotin, and picrotoxate (Scheme 10). 

The formation from farnesol of the picrotoxane skeleton of dendrobine (40) has been assumed to involve a 1,3 shift of the l-pro-R hydrogen in the germacrane intermediate (41), although no direct proof of this had been presented. The finding75... 

Systematic and Geographic Occurrence of Picrotoxane-Containing Plants... 

The first picrotoxanes discovered were isolated from the dried seeds of Menispermum cocculus (Anamirta cocculus) (1). Their characteristic features are two y-lactones and an oxrrane. M. cocculus belongs to the Menispermaceae ( moon seed family), which is in the order Ranunculales, and thus part of the primitive eudicots. So far, M. cocculus is the only species of the primitive eudicots recorded to contain picrotoxanes, and this species can be found in India, Sri Lanka, and southeast Asia. 

C. angustissima, C. pteroides, C. plumosa (New Zealand), and C. terminalis (Tibet), only C. nepalensis contains stmcturally deviant picrotoxanes, coriatone (53) and corianlactone (54) (69). Evidence of diurnal or seasonal fluctuation of picrotoxanes in plants has never been sought intentionally, but Jommi et al. (96) mentioned variable concentration levels of coriamyrtin and tutin in C. japonica. Thus the main picrotoxane, coriamyrtin, disappears in the autumn, when tutin (2-hydroxycoriamyr-tin) becomes the main picrotoxane. 

Guo et al. reported the isolation of picrotoxanes from Cuscuta japonica (Japanese dodder), a parasitic vine of many shrubs, growing in China, Korea, and Japan (41). This was the first report of a picrotoxane detected within the Asterid subclass of the core eudicots. The picrotoxanes of this member of the Convolvulaceae are also found as constituents of Coriaria species. As this plant is a parasite, it is possible that the picrotoxanes present were received from the sap of its host. 

That such a transfer as hypothesized in section 3.2.1 above does occur within Coriaria species and their parasites, plants, or animals, has been proven. Loranthaceae, relatives of the mistletoe (order Santalales core eudicots) grow on the twigs of Coriaria species. With the help of their haustorias they participate in the sap of their host. The picrotoxanes were extracted from the leaves of this parasitic plant. 

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