Synthesis of Orelline

Article abstract of DOI:10.1002/hlca.19880710503

Orelline (1), a metabolite of the toadstool Cortinarius Orellanus 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 79percent yield.Due to the chelating effect of the two SEM-ether groups in 5, it was possible to form selectively the dilithium compound 6 by an exchange reaction with BuLi at -50 deg C in Et2O.Reaction of 6 with electrophiles at -20 deg C afforded the 4- and 4,4'-substituted bipyridines 7-14 in excellent-to-reasonable yield.Oxidations of 6 with 2-(phenylsulfonyl)-3-phenyloxaziridin and with bis(trimethylsilyl)peroxide gave the 4,4'-diol 9 in 22 and 10percent 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 45percent 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 35percent 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.