N-glucosides of aminobenzoic acids and aminophenols

Article abstract of DOI:10.1023/B:CONC.0000018115.15793.d5

N-o-, -m-, and -p-carboxyphenyl-D-glucosylamines and N-o-, -m-, and -p-hydroxyphenyl-D-glucosylamines were synthesized by reaction of D-glucose with o-, m-, and p-aminobenzoic acids and o-, m-, and p-aminophenols. It was demonstrated that both β- and α-an

Full text of DOI:10.1023/B:CONC.0000018115.15793.d5

Chemistry of Natural Compounds, Vol. 39, No. 6, 2003
N-GLUCOSIDES OF AMINOBENZOIC ACIDS AND AMINOPHENOLS
R. Kublashvili
UDC 577.547.555.466
N-o-, -m-, and -p-carboxyphenyl-D-glucosylamines and N-o-, -m-, and -p-hydroxyphenyl-D-glucosylamines
were synthesized by reaction of D-glucose with o-, m-, and p-aminobenzoic acids and o-, m-, and p-
aminophenols. It was demonstrated that both β- and α-anomers were formed by N-glycosylation of o-, m-,
and p-aminobenzoic acids; only β-anomers, by N-glycosylation of o-, m-, and p-aminophenols.
Key words: N-glucosides, carboxyphenylglucosylamines, hydroxyphenylglucosylamines.
The synthesis and properties of N-glucosides are under intense scrutiny. On one hand, these products play a key role
in the formation of melanoidins [1], on the other, N-glucosylation is closely related to the metabolism of biologically active
aminesandproteins[2, 3]. These amines include alsoisomeric aminobenzoic acids and aminophenols. Aminophenols are often
formed as metabolites of several pesticides. Formation of N-glycosides via direct reaction of unsubstituted monosaccharides
with amines of moderate basicity (pKa 1-6) is a convenient method for preparative production of these compounds. We used
this method [4-6] to investigate glycosylation of isomeric aminobenzoic acids and isomeric aminophenols. We prepared,
isolated, and characterized via reaction of D-glucose with aminobenzoic acids and aminophenols in ethanol (96%) as solvent
and glacial acetic acid as catalyst the N-glucosides: N-o-carboxyphenyl-D-glucosylamine (1), N-m-carboxyphenyl-D-
glucosylamine(2), N-p-carboxyphenyl-D-glucosylamine(3), N-o-hydroxyphenyl-D-glucosylamine(4), N-m-hydroxyphenyl-D-
glucosylamine (5), and N-p-hydroxyphenyl-D-glucosylamine (6).
The basicity of the starting amine is known to have a strong influence on the yield of the desired N-glycoside. The
greater the basicity of the amine, the easier the resulting N-glycoside undergoes various conversions (hydrolysis,
Amadori—Haynes rearrangement, formation of melanoidins, etc.) [7]. As a result, increasing the basicityofthe starting amine
decreases the preparative yield ofthe target N-glycoside. Such a trend was observed in our experiments, in which the pKa values
of the amines used in the reactions and the yields of the corresponding N-glucosides were compared (Table 1).
The optimal conditions for the N-glucosylation were selected based on the amine properties. As a result, the target
product could be isolated quantitativelyfrom the reaction mixture. Under these conditions in ethanol (96%) using glacial acetic
acid as a catalyst, the N-glucosides were obtained in greatest yield from o- and p-aminobenzoic acids and from o- and m-
aminophenols (Table 1). After appropriate purification, the synthesized N-glucosides were identified by elemental analysis,
IR spectra, and 13C NMR spectra.
The analysis of the IR spectra should take into account the fact that most of the N-glycosides have cyclic pyranose
because their spectral properties are consistent with the presence of an amine N and a carbohydrate ring and the lack of >C=N
-
1
-1
[
(
8]. The following frequencies were observed for these N-glucosides: 750-760, 910-930 cm (cyclic pyranose), 1010-1030 cm
-1
-1
C –N stretching vibrations of the anomeric C ), 1130-1170 cm (carbohydrate ring vibrations), 1495-1515 cm (absorption
1
1
-1
-1
ofN-glucosidebond), 2850-2950cm (glucoseC–Hstretchingvibrations), 3200-3350cm (glucoseO–Hstretchingvibrations).
We interpreted the 13C NMR spectra taking into account that fact that the hemiacetal of the glucose hydroxyl is
aminated in this reaction. Therefore, the substituent has the greatest effect on C if the more electronegative O is replaced by
1
a less electronegative N. Such a substitution increases the electron density on C . As a result, it shifts to strong field by 10-
1
1
5 ppm. Therefore, this signal is easily identified from a group of signals and is located in the range 80-85 ppm. This resonant
frequency of C can be used as a specific indicator of C –N bond formation (N-glycoside formation).
1
1
I. DzhavakhishviliTbilisi State University, 380028, Georgia, Tbilisi, pr. I. Chavchavadze, 3. Translatedfrom Khimiya
Prirodnykh Soedinenii, No. 6, pp. 484-486, November-December, 2003. Original article submitted November 4, 2003.
©
0
009-3130/03/3906-0586$25.00 2003 Plenum Publishing Corporation
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TABLE 1. Yields and Properties of Synthesized N-Glucosylamines
Compound
Yield, %
mp, °C
pKa of starting amine
1. N-o-carboxyphenyl-D-glucosylamine
2. N-m-carboxyphenyl-D-glucosylamine
3. N-p-carboxyphenyl-D-glucosylamine
4. N-o-hydroxyphenyl-D-glucosylamine
5. N-m-hydroxyphenyl-D-glucosylamine
6. N-p-hydroxyphenyl-D-glucosylamine
~ 90
~75
~90
~60
~72
~55
124-125
113-114
126-127
115-118
87-88
2.11
3.12
2.41
4.72
7.17
5.17
92
1
3
TABLE 2. Chemical Shifts (ppm) in C NMR Spectra of Synthesized Phenyl-D-Glucosylamines
Compouns
Atom
1
2
3
4
5
6
β
α
β
α
β
α
β
β
β
α
Carbohydrate part
C-1
C-2
C-3
C-4
C-5
C-6
83.4
73.51
76.74
70.1
81.37
73.07
73.87
70.25
72.35
60.84
84.93
73.12
77.43
70.16
77.75
60.94
82.40
74.89
73.37
70.35
71.12
61.28
84.08
73.02
77.51
70.12
77.74
60.93
81.59
71.81
73.3
85.8
73.13
77.48
70.35
77.49
60.99
85.19
73.09
77.26
70.15
77.68
60.93
82.98
75.7
81.34
76.29
70.5
70.56
70.96
61.94
77.54
61.21
77.2
63.31
63.03
Aromatic nucleus
C-1
C-2
149.75
111.1
131.28
113.2
134.3
116.1
169.7
149.86
111.5
147.49
114.1
131.3
118.1
117.18
129.0
167.9
147.78
151.6
112.6
131.3
118.6
131.3
112.6
167.6
151.5
112.3
131.0
135.7
144.1
112.1
117.15
119.6
13.65
148.6
100.25
157.0
103.3
129.4
104.6
142.05
115.6
113.7
148.5
113.7
115.6
114.5
C-3
113.8
113.8
C-4
113.5
169.6
118.3
116.7
C-5
131.0
112.3
C-6
COOH
Ratio of β- and α-anomers
18.9 86.67 13.33
%
60.87
39.13
81.1
100
100
100
Spectra of N-o-, -m-, and -p-carboxyphenyl-D-glucosylamines (1, 2, and 3, respectively) were separated into three
principal ranges, of which C atoms bound to primary and secondaryalcohols of the glucose resonate at strongest field. C atoms
bound to two electronegative atoms (O–C–N) resonate at weakest field. The chemical shift of the β-conformer of any
monosaccharide (except mannose) is known to be greater than that of the α-conformer [9-12]. Therefore, the signal located
at 80-85 ppm at comparatively weak field belongs to the β-anomer of glucose; the signals located at comparativelystrong field,
to the α-anomer. Table 2 gives the ratios of β- and α-anomers calculated taking into account the duration of the reaction of
the anomeric C and the strength of the signal and the assignments of the glucose C atoms in addition to the C atoms of the
o-, m-, and p-aminobenzoic acids and o-, m-, and p-aminophenols of N-glucosides. Among the remaining signals, that of the
C-5 ring defining the configuration of the glucose, the chemical shift of which is ~77 ppm for all glucose β-conformers, should
be noted.
Compounds 4-6 were prepared by reaction of o-, m-, and p-aminophenols with glucose. They differ from 1-3 mainly
in that exclusively the β-conformers are formed in the first instance.
587

EXPERIMENTAL
IR spectra were recorded on a Specord 75 IR spectrophotometer in KBr; 13C NMR spectra, on a Bruker WM-250 MHz
instrument. The standard was (CD ) SO with a shift of the central signal at 39.505 ppm for complete C–H decoupling. The
3
2
sample size was 30 mg. Spectra were recorded at 60°C. Melting points were determined in a Kofler apparatus. The rate of
temperature rise near the melting point was 4° per minute.
Synthesis of Carboxyphenyl- and Hydroxyphenyl-D-glucosylamines. A mixture of D-glucose (0.01 mol); o-, m-,
p-aminobenzoic acid or o-, m-, p-aminophenol (0.0107 mol); ethanol (15 mL, 96%), water (0.5 mL), and glacial acetic acid
(0.3 mL) was heated on a boiling-water bath with stirring until the starting materials dissolved completely. The mixture was
cooled to room temperature, treated with diethylether (50 mL), stirred, and left overnight. The resulting crystalline precipitate
was filtered off, ground with ethanol (96%), and treated with diethylether. After thorough mixing, the precipitate was filtered
off. The resulting N-glucoside was purified by reprecipitation from alcoholic solution by diethylether. The purity of the
compoundswasmonitoredusingTLCon SilufolUV-254plates(dioxane:benzene, 1:4for aminobenzoicacids; benzene:ethanol,
9
:1 for aminophenols; CHCl :CH OH, 19:5 for glucose). Sugar was developed byalkaline KMnO and sodium metaperiodate;
3 3 4
aminobenzoic acids and aminophenols, by alchoholic 4-dimethylaminobenzaldehyde.
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