Picrotoxanes lactones

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. 

To demonstrate the versatility of his S3mthesis strategy Yamada used ketoester 151 as relais substance to S3mthesize two further picrotoxane alkaloids isolated from Dendrobium species, nobilonine (90) and 2-hydroxydendrobine (87) (Scheme 14) (84). Monobromination of 151 with bromine in dioxane and subsequent treatment with water resulted in hydroxy-y-lactam 152, whereas attempts to hydroxylate 151 by Barton oxidation led to rearrangements. Chemo- and stereoselective reduction with zinc borohydride converted 152 into the en fo-alcohol. To counterbalance the unfavorable conformational equilibrium this alcohol had to be converted into the alcoholate to achieve lactonization. Chemoselective reduction of the hydroxylac-tam moiety of lactone 153 again followed Borch s protocol, which led in this case to boron complexed amino compounds necessitating successive acid treatment to obtain racemic 2-hydroxydendrobine (87) in low yield accompanied by dendrobine (82). 2-Hydroxydendrobine (87) was converted into nobilonine (90) by Eschweiler-Clark methylation. 

Picrotoxin and coriaria lactone (mainly a mixture of tutin (11) and coriamyrtin (9)) as well as many other picrotoxanes, are epileptogenic compormds and they are used to induce epilepsy in laboratory animals to test newly developed antiepileptic compounds (259). Their importance may be seen from the fact that recent estimations show that 0.4—1 % of the population suffers from epileptic seizures, with one-third of the sufferers being younger than 16-years-old, and that the average duration of the disease is 12.5 to 25 years 260). 

Nagahisa M, Koike K, Narita M, Ohmoto T (1994) Novel Picrotoxane Norditerpene Lactones from Picrodendron baccatum. Tetrahedron 50 10859... 

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. 

Lactones, synthesis by pericyclic photochemical reactions 86YGK1O58. Natural lactones with carbon skeleton of picrotoxane, synthesis of ... 

Coriamycin (30) is a member of the picrotoxane sesquiterpenes it stimulates the central nervous system, similar to the activity of the better known picro-toxinin. In a general route for the construction of the picrotoxane carbon skeleton, Tanaka et al have described a stereocontrolled synthesis of (30), starting from the product (26) resulting from l,6>addition of 2-methylcyclopentane-l,3-dione to protoanemonin (25). Methanolysis of (26) led to (27), which was converted into (28) by addition of isopropenylmagnesium bromide. The latter was then converted into coriamycin (30) via the intermediate lactone (29). 

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