Synthese von Orellin

Synthesis of Orelline Orelline (1) , a metabolite of the toadstool Cortinarius Overllauns Fries with 2,2′-bipyridine structure, has been synthesized by the following method. The easily accessible 2-bromo-3-hydroxypyridine (3) was converted into the corresponding 2-(trimethylsilyl)ethoxy]methyl (SEM) ether 4 and coupled with Zn and NiCl₂/Ph₃P to form the bipyridine derivative 5 in 79% yield. Due to the chelating effect of the two SEM-ether groups in 5 , it was possible to from selectively the dilithium compound 6 by an exchange reaction with BuLi at ?50° in Et₂O. Reaction of 6 with electrophiles at ?20° afforded the 4- and 4,4′-substituted bipyridines 7–14 in excellent-to-reasonable yield. Oxidation of 6 with 2-(phenylsulfonyl)-3-phenyloxaziridin and with bis(trimethylsilyl)peroxide gave the 4,4′-diol 9 in 22 and 10% yield, respectively. Methanolysis of 9 directly afforded crystalline 1 in high yield, with properties identical with those of natural orelline. Formylation of 6 with N-formylmorpholine gave 45% of the dicarbaldehyde 13. Removal of the SEM groups in 13 by hydrolysis afforded the dihydroxydicarbaldehyde 15 that could be oxidized to 1 with alkaline H₂O₂. Attempts to oxidize 1 to orellanine (2) with 35% H₂O₂ according to a known procedure were unsuccessful (cf. Exper. Part). Compound 7 with two Me₃Si groups in 4,4′-position gave after methanolysis the fluorescence dye 16 with an appreciable Stokes shift in cyclohexane.