Picrotoxanes from Dendrobium Species

Porter (2) and Coscia (3) described the structures of six dendrobine alkaloids and one dendrobium salt. Although the structures of the dendrobines are less complex than those of most other picrotoxanes, their structure determination became feasible only after spectroscopic methods became generally available in the 1960s. Thus, in 1964, no less than three Japanese research groups completed independently the structure determination of dendrobine (82), the main alkaloid of D. nobile, using a combination of degradation reactions and spectroscopic data analysis (136-138). 

A-Methyldendrobinium chloride (84) was the first quaternary picrotoxane alkaloid isolated and characterized by Inubushi 114). The next dendrobinium salt isolated was A-isopentenyldendrobinium chloride (85) 81). Its structure was determined by pyrolysis to dendrobine (82). The configuration of its quaternary nitrogen was determined by synthesis 81). 

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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. 

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