Picrotoxanes Dendrobium species

So far, Dendrobium species have yielded 21 pseudoalkaloids of the picrotoxane type and 27 sesquiterpene picrotoxanes (5 dilactones, 20 monolactones. 

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. 

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. 

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