Picrotoxanes biosynthesis

The first report of the incorporation of radioactively labelled mevalonic acid into dendrobine (82) was by Yamazaki et al. (224). Sodium [2— CJmevalonate [( )-463 ] was administered to stems of D. nobile by the cotton-wick method. After 12 days, the plants were extracted and radioactive dendrobine (82) was isolated by column chromatography. The total incorporation was 0.012%. Subsequent Kuhn-Roth oxidation led to acetic acid that showed the expected activity assuming the biosynthesis pathway a leading to the picrotoxanes via a cadalene as precursor (Scheme 55, pathway c). 

Although investigations of biosynthesis have become considerably more convenient by shifting to stable isotopes and nondestructive spectroscopic methods, the pioneering work was never continued. Thus, the pathway from copabomeol (474) to dendrobine (82), mono- and dilactone picrotoxanes, and norditerpene picrotox-anes is stiU unknown and no enzymes of this biosynthetic pathway have been defined or isolated. There is mention of genes of the dendrobine bios3mthesis isolated and expressed in Escherichia coli (233). 

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