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Synthese von Orellin
Author(s) -
Hasseberg HansAlbrecht,
Gerlach Hans
Publication year - 1988
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19880710503
Subject(s) - chemistry , formylation , trimethylsilyl , yield (engineering) , medicinal chemistry , electrophile , ether , hydrolysis , oxonium ion , derivative (finance) , organic chemistry , catalysis , ion , materials science , economics , financial economics , metallurgy
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 NiCl 2 /Ph 3 P 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 Et 2 O. 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 H 2 O 2 . Attempts to oxidize 1 to orellanine (2) with 35% H 2 O 2 according to a known procedure were unsuccessful ( cf. Exper. Part ). Compound 7 with two Me 3 Si groups in 4,4′‐position gave after methanolysis the fluorescence dye 16 with an appreciable Stokes shift in cyclohexane.