Russian Journal of Bioorganic Chemistry, Vol. 27, No. 6, 2001, pp. 385–389. Translated from Bioorganicheskaya Khimiya, Vol. 27, No. 6, 2001, pp. 434–438.
Original Russian Text Copyright © 2001 by Kur’yanov, Chupakhina, Zemlyakov, Kotlyar, Kamalov, Chirva.
Synthesis of N-Acetylglucosamine Aryl b-Glycosides Catalyzed
by Crown Compounds
V. O. Kur’yanov*, T. A. Chupakhina*, A. E. Zemlyakov*, S. A. Kotlyar**,
1
G. L. Kamalov**, and V. Ya. Chirva*
*Vernadsky Tauric National University, ul. Yaltinskaya 4, Simferopol, 95007 Ukraine
**Bogatsky Physicochemical Institute, National Academy of Sciences of Ukraine,
Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine
Received January 15, 2001; in final form, April 19, 2001
Abstract—Glycosylation of various phenols with α-D-glucosaminyl chloride peracetate in a solid phase–liq-
uid system catalyzed by crown compounds was studied. The highest yields of aryl β-glycosides were observed
at room temperature in acetonitrile using anhydrous potassium carbonate as a base. The optimum phenol–gly-
cosyl donor–base–crown ether ratio was 1 : 1 : 1 : 0.2.
Key words: glycosylation, aryl glycosides, N-acetylglucosamine glycosides, crown ether
1
INTRODUCTION
The reaction time did not usually exceed 24 h.
Unsubstituted phenol, β-naphthol, and their derivatives
were subjected to glycosylation. The glycosylation
products were isolated by crystallization. The yields of
glycosides (IIa)–(IIq) were 43–86%. In all cases only
β-glycosides of N-acetylglucosamine formed as was
demonstrated by the presence in their 1H NMR spectra
of the doublets of anomeric protons with the chemical
shift in a range of 5.15–5.47 ppm and a coupling con-
stant of 8–9 Hz (Table 1). The chemical shifts and the
splitting of the proton signals of phenolic aglycons cor-
related with their structures. The signals of the back-
bone protons of the carbohydrate residues in all the
products are characterized by similar values of chemi-
cal shifts and coupling constants.
A decrease in the proportion of 15-crown-5 to 1 mol %
diminished the reaction rate and, consequently, the
yield of the target glycosides. The enhancement of the
amount of the catalyst, base, or phenol had practically
no influence on the results of the synthesis. The substi-
tution of dibenzo-18-crown-6 for 15-crown-5 also had
no effect on the reaction time and the glycoside yield.
The best results for the glycosylation of phenol with
chloride (I) were observed with acetonitrile as a solvent
and potassium carbonate as a base (Table 2). The rise of
the temperature of the reaction mixture up to 50–52°ë
resulted in a drop of the reaction time but simulta-
neously diminished the yield of glycoside (II‡). At a
higher temperature, the products of the chloride (I)
destruction prevailed along with a small amount of
oxazoline (III).
Carbohydrate aryl glycosides, including those of
N-acetylglucosamine, have been extensively investi-
gated as substrates in the studies on enzyme specificity
(e.g. [1]), potential anti-infectious preparations [2, 3],
2
and spacers [4]. MDP phenyl β-glycoside has dis-
played a high protective activity against Salmonella
typhi [5]. At present, the phase-transfer catalysis with
quaternary ammonium salts as catalysts [7, 8] is widely
used for obtaining N-acetylglucosamine aryl glyco-
sides along with such classic methods as oxazoline syn-
thesis [6] and interaction of phenolates or phenols with
2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-glucosami-
nyl chloride (I) in the presence of various bases in polar
aprotic solvents [2, 9, 10].
RESULTS AND DISCUSSION
When attempting to simplify the scheme for obtain-
ing MDP aryl glycosides, we established the synthesis
of phenolic glycosides of N-acetylglucosamine in the
solid phase–liquid system catalyzed by crown ethers to
be rather convenient. Glycosylation of phenols with an
equimolar amount of chloride (I) was performed in ace-
tonitrile at room temperature in the presence of an
equimolar amount of finely powdered anhydrous potas-
sium carbonate and 20 mol % of 15-crown-5 ether. The
method suggested does not need excess phenolic com-
pound, is methodically facile, and requires mild, non-
destructive conditions.
As a rule, the glycosylation of phenols harboring
electron acceptor substituents proceeded more slowly
than the formation of aryl glycosides from phenols with
electron donor groups, but with higher yields (Table 3).
1
To whom correspondence should be addressed; phone: +38
(0652) 23-3885; fax: +38 (0652) 23-2310.
2
Abbreviations: MDP, muramyl dipeptide, N-acetylmuramyl-L-
alanyl-D-isoglutamine.
1068-1620/01/2706-0385$25.00 © 2001 MAIK “Nauka /Interperiodica”
Kur'yanov
