Total synthesis of orellanine : The lethal toxin of Cortinarius Orellanus fries mushroom

The syntheses of the main toxin of Cortinarius Orellanus Fries, orellanine, and of its decomposition product, orelline, are reported. The structures of 3,3',4,4'-tetrahydroxy-2,2'-bipyridyl-N,N'-dioxide for orellanine and of 3,3',4,4'-tetrahydroxy-2,2'-bipyridyl for orelline have been proposed by W.Z. Antkowiak and W.P. Gessner. These two conpounds have now been synthesized starting from the 3,3',4,4'-tetramethoxy-2,2'-bipyridyl which could be obtained in good yields by the nickel-phosphine complex-mediated homo coupling of 2-bromo-3,4-dimethoxy pyridine according to the general procedure previously reported by us. The 3,3',4,4'-tetrahydroxy-2,2'-bipyridyl was obtained by demethylation with hydrobromic acid. The oxidation of this compound with hydrogen peroxide afforded the 3,3',4,4'-tetrahydroxy-2,2'-bipyridyl-N,N'-dioxide. This latter compound was also obtained by the demethylation of the 3,3',4,4'-tetramethoxy-2,2'-bipyridyl-N,N'-dioxide with hydrobromic acid. The products obtained presented physical and spectral properties identical to those of the natural products.