Synthese von Orellin

Abstract

Synthesis of OrellineOrelline (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.