An improved procedure for the synthesis of N-bromoacetyl-β- glycopyranosylamines, derivatives of mono- and disaccharides

Article abstract of DOI:10.1023/B:RUCB.0000035661.45796.f7

An improved procedure for the synthesis of N-bromoacetyl-β- glycopyranosylamines from the corresponding β-glycosylamines was developed. The procedure is applicable to a wide range of derivatives of monosaccharides (hexoses, 2-acetamido-2-deoxyhexoses, hexuronamides, and 6-deoxyhexoses) and some disaccharides. For the derivatives of pentoses and 2-deoxyhexoses, the use of the corresponding β-glycosylammonium carbamates was found to be more convenient. N-Bromoacetyl-β-glycopyranosylamines derived from D-mannose, L-rhamnose, D-glucuronamide, 2-deoxy-D-arabino-hexose, 2-deoxy-D-lyxo-hexose, and melibiose were obtained for the first time.

Full text of DOI:10.1023/B:RUCB.0000035661.45796.f7

Russian Chemical Bulletin, International Edition, Vol. 53, No. 3, pp. 709—713, March, 2004
709
An improved procedure for the synthesis
of Nꢀbromoacetylꢀβꢀglycopyranosylamines,
derivatives of monoꢀ and disaccharides
L. M. Likhosherstov,ꢀ O. S. Novikova, A. O. Zheltova, and V. N. Shibaev
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninskii prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: shiba@ioc.ac.ru
An improved procedure for the synthesis of Nꢀbromoacetylꢀβꢀglycopyranosylamines from
the corresponding βꢀglycosylamines was developed. The procedure is applicable to a wide
range of derivatives of monosaccharides (hexoses, 2ꢀacetamidoꢀ2ꢀdeoxyhexoses, hexuronꢀ
amides, and 6ꢀdeoxyhexoses) and some disaccharides. For the derivatives of pentoses and
2ꢀdeoxyhexoses, the use of the corresponding βꢀglycosylammonium carbamates was found to
be more convenient. NꢀBromoacetylꢀβꢀglycopyranosylamines derived from Dꢀmannose,
Lꢀrhamnose, Dꢀglucuronamide, 2ꢀdeoxyꢀDꢀarabinoꢀhexose, 2ꢀdeoxyꢀDꢀlyxoꢀhexose, and meliꢀ
biose were obtained for the first time.
Key words: Nꢀbromoacetylꢀβꢀglycopyranosylamines, βꢀglycopyranosylamines, βꢀglycoꢀ
pyranosylammonium carbamates, Nꢀbromoacetylation.
In recent years, glycosylamines have found increasꢀ
ingly wide application for the preparation of natural glyꢀ
copeptides, their analogs, and glycoconjugates for various
biological investigations. Within the scope of our program
aimed at obtaining glycoconjugates of physiologically acꢀ
tive substances, we previously developed the convenient
routes to glycopyranosylamines starting from different
classes of monosaccharides (hexoses, 2ꢀacetamidoꢀ2ꢀ
deoxyhexoses, pentoses, and 6ꢀ and 2ꢀdeoxyhexoses) and
some disaccharides1—5 and converted them into the corꢀ
responding chloroacetamide derivatives,3 which were then
used to synthesize glycoconjugates of some biologically
active amines6 and amino acids,7 as well as to prepare
Nꢀglycylglycopyranosylamines for use in the synthesis of
glycoconjugates of carboxylic acids.8 The goal of the
present study was to develop a convenient procedure for
the preparation of Nꢀbromoacetylꢀβꢀglycopyranosylꢀ
amines, which can open up new opportunities for the
synthesis of glycoconjugates of new types of physiologiꢀ
cally active substances.
Earlier, syntheses of several Nꢀbromoacetylglycoꢀ
pyranosylamines have been described. Derivatives of
βꢀDꢀglucose,9—12 βꢀDꢀgalactose,9,10,13 NꢀacetylꢀβꢀDꢀgluꢀ
cosamine,12—15 and βꢀDꢀxylose16,17 were synthesized for
the introduction of an affinity label into active sites of
glycosidases,10,11,16—19 the preparation of glycopeptide
analogs,12,13 and the study of their cytotoxicity.14,20 The
syntheses of analogous derivatives of Lꢀglucose,10 Lꢀfuꢀ
cose,9,10 and some disaccharides9—12 were also reported.
The synthesis usually involves acylation of glycosylamines
with (BrCH2CO)2O in various solvents; the yields of the
same compounds obtained by different authors often difꢀ
fer noticeably.
This prompted us to investigate in more detail the
conditions of the synthesis of Nꢀbromoacetylglycosylꢀ
amines from glycosylamines with special emphasis on the
glycosylamines differing in stability.
Based on the results of our previous studies on the
synthesis of Nꢀchloroacetylglycosylamines3 and the availꢀ
able literature data, we investigated reactions of various
glycosylamines 1 with (BrCH2CO)2O in DMF leading to
Nꢀbromoacetylglycosylamines 2 (Scheme 1).
Because this anhydride is commercially inaccessible,
we describe a convenient procedure for its preparation,
which is based on the general method for the synthesis of
carboxylic acid anhydrides,21 which, to our knowledge,
has not been applied for the preparation of this comꢀ
pound.
The starting βꢀglycopyranosylamines, namely, monoꢀ
saccharide and disaccharide derivatives (1a—f and 1h,i),
were prepared from the corresponding sugars by the reꢀ
cently developed method4,5 using ammonium carbamate
as the aminating reagent. We used the same method to
synthesize an analogous Dꢀglucuronamide derivative 1g
starting from Dꢀglucuronoꢀγꢀlactone 3 via glycosylꢀ
ammonium carbamate 4g in 55% total yield (Scheme 2).
Optimization of the conditions for Nꢀbromoacetylaꢀ
tion of hexoseꢀderived glycosylamines (reaction mixtures
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 676—680, March, 2004.
1066ꢀ5285/04/5303ꢀ0709 © 2004 Plenum Publishing Corporation

710
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
Likhosherstov et al.
Scheme 1
Scheme 2
i. NH2COONH4/MeOH. ii. EtNPri2/MeOH—H2O.
hexose derivatives (1b and 1d,e) occurred more efficiently
in tetramethylurea (TMU). Products 2d and 2e crystalꢀ
lized directly from the reaction mixture; bromoacetamide
2b was crystallized upon the addition of MeOH. Apart
from the aforementioned hexose and 6ꢀdeoxyhexose deꢀ
rivatives (Dꢀmannose, Lꢀrhamnose, and Dꢀglucuronamide
derivatives have not been described earlier), lactose and
melibiose bromoacetamide derivatives (2h and 2i) were
smoothly obtained under similar conditions (in DMF and
DMF—TMU, respectively).
Preparation of analogous derivatives of pentoses and
2ꢀdeoxyhexoses was more efficient if fairly stable glycosylꢀ
ammonium carbamates rather than glycosylamines themꢀ
selves, which are difficult to prepare in the pure state
Table 1. Synthesis of Nꢀbromoacetylꢀβꢀglycosylamines from
glycosylamines (–8 °C, [(BrCH2CO)2O]/[glycosylamine] =
1.1—1.2)
a
b
Glycoꢀ
sylamine
C0 /M
Solvent
τ /h Reaction
Yield
(%)
product
were analyzed by paper chromatography) showed that the
main reaction is accompanied by several side processes
such as Oꢀacylation, the formation of ninhydrinꢀpositive
products (probably, as a result of Nꢀalkylation of the
unconsumed glycosylamine with a bromoacetamido deꢀ
rivative), and the decomposition of glycosylamine into
the free sugar. To suppress these side processes, a slight
excess of the acylating reagent (the anhydride : substrate
molar ratio is 1.1 to 1.2) and reduced reaction temperaꢀ
ture are substantial.
1a
1b
1c
1d
1e
1f
1g
1h
1i
0.7
0.4
0.9
0.6
0.6
0.9
0.5
0.3
0.15
DMF
TMU
DMF
TMU
TMU
DMF
DMF
DMF
3.5
5
2a
2b
2c
2d
2e
2f
2g
2h
2i
41
54
39
57
51
52
57
66
39
3.5
3.5
3.5
3.5
3
5
5
DMF—
TMU, 1 : 1
Under these conditions, Nꢀbromoacetylꢀβꢀglycoꢀ
pyranosylamines 2a,c,f,g were obtained in DMF (Table 1).
The reaction products can easily be isolated by crystalliꢀ
zation (except for 2g, which was purified by chromatoꢀ
graphy on SiO2). NꢀAcylation of Dꢀgalactose and 6ꢀdeoxyꢀ
a The initial concentration is the amount of the starting comꢀ
pound (mmol) per milliliter of the solvent. This value is apꢀ
proximate since the substrate is dissolved incompletely at the
initial reaction moment.
b Reaction time.

NꢀBromoacetylꢀβꢀglycopyranosylamines
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
711
because of their lability, were subjected to Nꢀbromoꢀ
acetylation. These salts have been described by us earꢀ
lier.4,5 This version of the reaction was applied for
the preparation of Dꢀxylose, 2ꢀdeoxyꢀDꢀarabinoꢀhexose,
and 2ꢀdeoxyꢀDꢀlyxoꢀhexose derivatives (4j, 4k, and 4l)
(Scheme 3).
this type of compounds which was developed as a result of
a series of experiments involved the use of a sterically
hindered tertiary amine (EtNPri2) in aqueous methanol.
Using this procedure, we obtained additional amounts of
bromoacetamides 2j and 2k (see Note to Table 2).
NꢀBromoacetylglycosylamines of 2ꢀdeoxyhexoses (2k
and 2l) have not hitherto been described; the yield of
Dꢀxylose derivative 2j from glycosylammonium carbamꢀ
ate 4j is noticeably higher than that from the correspondꢀ
ing glycosylamine.16,17
Scheme 3
The structures of the Nꢀbromoacetylꢀβꢀglycopyranoꢀ
sylamines obtained were confirmed by elemental analysis
1
data and NMR spectra. The H NMR spectra contain
characteristic signals for the protons of the BrCH2CO
group (δ 3.95—4.00) and the H(1) atom of the sugar resiꢀ
due (δ 4.90—5.05 (d, J = 8.5—9.5 Hz) for compounds
with the glucoꢀ and galactoꢀconfigurations and δ ∼5.2 for
2ꢀdeoxyhexoses (dd, J = 2.5 and 10.5 Hz) and comꢀ
pounds with the mannoꢀconfiguration). For Dꢀmannose
and Lꢀrhamnose derivatives, the chemical shifts of the
signal for C(3) (δC ∼74.0) unambiguously suggest the
βꢀconfiguration of the products.
Thus, we have improved the procedure for the synꢀ
thesis of Nꢀbromoacetylꢀβꢀglycopyranosylamines from
βꢀglycopyranosylamines, which is applicable to a wide
range of this class of compounds (derivatives of hexoses,
2ꢀacetamidoꢀ2ꢀdeoxyhexoses, hexuronamides, 6ꢀdeoxyꢀ
hexoses, and disaccharides). It was demonstrated that
Nꢀbromoacetyl derivatives of pentoses and 2ꢀdeoxyꢀ
hexoses are more conveniently obtained from the correꢀ
sponding βꢀglycosylammonium carbamates.
In this case, the use of a greater excess of the acylating
reagent is required (the anhydride : substrate molar ratio
is 1.7 to 2.0), which noticeably increases the yields of
Oꢀacylated byꢀproducts. Nevertheless, satisfactory yields
of bromoacetamide derivatives 2j—l were attained upon
chromatographic separation of the reaction mixtures on
SiO2 (Table 2).
Additional amounts of the target products were obꢀ
tained by Oꢀdeacylation of compounds with higher chroꢀ
matographic mobilities. The Oꢀdeacylation procedure
used by us earlier in the synthesis of Nꢀchloroacetylꢀ
glycosylamines3 (Et3N in aqueous MeOH) proved to be
unsatisfactory in the case of bromoacetamido derivatives
because of substantial substitution of bromine under these
conditions. An efficient procedure for Oꢀdeacylation of
Experimental
1
H and 13C NMR spectra were recorded on a Bruker
WMꢀ250 spectrometer (250 (1H) and 62.7 MHz (13C)) in CDCl3
and D2O at 24 °C with residual solvent protons as the internal
standard or acetone as the external standard. Optical rotations
were determined on a PUꢀ5 polarimeter (Russia). Electrophoreꢀ
sis was performed on Filtrak FN1 paper in 6% HCOOH
(12 V cm–1, 1 h). For ascending chromatography, Filtrak FN15
paper and BunOH—AcOH—H2O (4 : 1.4 : 2.5) as the solvent
system were used. The substances were detected with ninhydrin
and KIO4—AgNO3—KOH in succession. Water of crystallizaꢀ
tion was determined by the Fischer method.
Table 2. Synthesis of Nꢀbromoacetylꢀβꢀglycosylamines from
glycosylammonium carbamatesa
b
b
Glycoꢀ
sylamine
C0 /M
Solvent
τ /h Reaction
Yield
(%)
Bromoacetic anhydride. From a solution of bromoacetic acid
(20.8 g, 0.15 mol) in 50 mL of Ac2O (0.45 mol) and 120 mL of
toluene, the solvent (20 mL) was distilled off in vacuo to remove
residual AcOH and water. The residue was kept at 80 °C for 3 h.
The solvent was removed at 70 Torr, and the residue was disꢀ
tilled in vacuo with protection against moisture. The last highꢀ
boiling fraction (b.p. 117—119 °C, 10 Torr) was collected. The
yield of the anhydride was 12.5 g (64%) (cf. Ref. 22: b.p.
121—125 °C (11 Torr)). 1H NMR (CDCl3), δ: 3.98 (s, CH2); for
bromoacetic acid: 3.89 (s, 2 H, CH2); 9.80 (br.s, 1 H, OH).
Glycosylamines 1a—f,h,i and glycosylammonium carbamates
4j—l were synthesized as described earlier.4,5
product
4j
4k
4l
0.8
0.4
0.4
DMF
TMU
DMF
5
5 d
1
2j
2k
2l
41 c
47 c
33
a Reaction conditions: –8 °C, [(BrCH2CO)2O]/[carbamate] =
1.7 (4j), 2.0 (4k,l).
b See Notes to Table 1.
c The additional amount of the product (12—14%) was obtained
upon Oꢀdeacylation.
d At 0 °C.

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
Likhosherstov et al.
20
(βꢀDꢀGlucopyranosylamine)uronamide (1g). Powdered
compound 2c, m.p. 191—192 °C, [α]D –29.0 (c 1, H2O).
Found (%): C, 32.41; H, 4.83; Br, 26.69; N, 4.89. C8H14BrNO6.
Calculated (%): C, 32.02; H, 4.70; Br, 26.62; N, 4.67. 1H NMR,
δ: 3.43 (m, 1 H, H(5)); 3.56 (t, 1 H, H(4), J3,4 = J4,5 = 10.0 Hz);
3.68—3.77 (m, 2 H, H(3), H(6a)); 3.84 (m, 1 H, H(6b)); 3.93
(m, 1 H, H(2)); 3.97 (br.s, 2 H, CH2); 5.18 (br.s, 1 H, H(1)).
13C NMR, δ: 28.7 (CH2); 61.6 (C(6)); 67.2 (C(4)); 70.7 (C(2));
74.0 (C(3)); 78.7 (C(5)); 78.9 (C(1)); 170.1 (CO).
Dꢀglycofuranurono(6→3)lactone 3 (0.53 g, 3 mmol) (Fluka) was
dissolved at 55 °C in MeOH (15 mL) and cooled. Powdered
ammonium carbamate (0.94 g, 12 mmol) was added, and the
reaction mixture was stirred to homogeneity and left at 20 °C
for 16 h. The reaction mixture with the resulting precipitate
was kept at 0 °C for 5 h. The precipitate was filtered off,
washed with MeOH—PriOH (2 : 1) and ether, and dried to
give (βꢀDꢀglucopyranosylammonium)uronamide carbamate 4g
NꢀBromoacetylꢀβꢀLꢀrhamnopyranosylamine (2d). The stirred
reaction mixture with a gelꢀlike precipitate was diluted with
acetone (3 vol.). The precipitate was filtered off, washed with
acetone and ether, and dried to give compound 2d, m.p.
20
(0.68 g, 89.5%), m.p. 140—143 °C, [α]D –12.5→–9.0 (c 1,
H2O, after 5 and 15 min). Found (%): C, 33.26; H, 6.06;
N, 16.48. C6H12N2O5•NH2COOH. Calculated (%): C, 33.20;
H, 5.97; N, 16.59.
20
142—144 °C, [α]D +38.3 (c 1, H2O). Found (%): C, 32.13;
Ethyl(diisopropyl)amine (0.4 mL, 2.36 mmol) and MeOH
(60 mL) were added to a stirred solution of carbamate 4g (0.5 g,
2 mmol) in 3 mL of water. The solution was concentrated at
70 Torr to 10 mL, diluted with MeOH to 40 mL, and concenꢀ
trated again analogously. A MeOH—PriOH mixture (5 : 1)
(18 mL) was added, and the solution was concentrated to 2 mL.
The precipitate that formed was filtered off, washed with
MeOH—PriOH (2 : 1) and ether, and dried to give glycosylꢀ
H, 5.43; Br, 26.89; N, 4.40; H2O, 5.44. C8H14BrNO5•H2O.
Calculated (%): C, 31.80; H, 5.34; Br, 26.45; N, 4.64; H2O, 5.96.
1H NMR, δ: 1.29 (d, 3 H, CH3, J = 5.9 Hz); 3.33—3.53 (m, 2 H,
H(4), H(5)); 3.67 (dd, 1 H, H(3), J2,3 = 3.4 Hz, J3,4 = 9.4 Hz);
3.96 (br.d, 1 H, H(2), J = 3.4 Hz); 4.00 (s, 2 H, CH2); 5.20 (br.s,
1 H, H(1)). 13C NMR, δ: 17.6 (CH3); 28.7 (CH2); 70.8 (C(2));
72.5 (C(4)); 73.8 (C(3)); 74.8 (C(5)); 78.8 (C(1)); 171.0 (CO).
NꢀBromoacetylꢀβꢀLꢀfucopyranosylamine (2e). The stirred reꢀ
action mixture with a precipitate was diluted with acetone—ether
(1 : 1, 3 vol.). The precipitate was filtered off, washed with this
mixture and ether, and dried to give compound 2e, m.p.
20
amine 1g (0.23 g, 60.7%), m.p. 144—146 °C, [α]D –9.0 (c 1,
H2O, after 10 min). Found (%): C, 37.87; H, 6.40; N, 14.67.
C6H12N2O5. Calculated (%): C, 37.50; H, 6.29; N, 14.58.
1H NMR, δ: 3.17 (m, 1 H, H(2)); 3.47 (m, 2 H, H(3), H(4));
3.82 (m, 1 H, H(5)); 4.11 (d, 1 H, H(1), J = 8.8 Hz).
NꢀAcylation of glycosylamines 1a—i or glycosylammonium
carbamates 4j—l (general procedure). A suspension of a powꢀ
dered glycosylamine or carbamate in dry DMF or TMU was
cooled to –8 or 0 °C and bromoacetic anhydride was added. The
reaction mixture was stirred to homogeneity and kept at this
temperature for 1 to 5 h (see Tables 1, 2). The isolation proceꢀ
dure and characteristics of Nꢀbromoacetyl derivatives 2a—l are
described below.
20
169—171 °C (from MeOH—Et2O), [α]D –0.7 (c 3, H2O);
cf. Refs. 9 and 10: m.p. 175 °C, [α]D20 +2.8 (c 1, H2O). 1H NMR,
δ: 1.24 (d, 3 H, Me, J = 6.5 Hz); 3.63 (m, 1 H, H(2)); 3.72 (m,
1 H, H(3)); 3.81 (m, 1 H, H(4)); 3.88 (m, 1 H, H(5)); 3.96 (s,
2 H, CH2); 4.91 (d, 1 H, H(1), J = 8.5 Hz).
2ꢀAcetamidoꢀNꢀbromoacetylꢀ2ꢀdeoxyꢀβꢀDꢀglucopyranosylꢀ
amine (2f). Ether (1 vol.) was added to a stirred reaction mixꢀ
ture, which was then kept at –10 °C for 16 h. The precipitate
that formed was filtered off, washed with acetone and ether,
and dried to give compound 2f, m.p. 201—202 °C (from
20
NꢀBromoacetylꢀβꢀDꢀglucopyranosylamine (2a). The reaction
mixture was poured into 10 volumes of ether with stirring and
kept at –10 °C for 16 h. The precipitate was separated by decanꢀ
tation, repeatedly (five times) triturated with ether, and dried.
The residue was dissolved at 20 °C in a minimum amount of
DMF, and PriOH (2.5 vol.) was added. The mixture was kept at
–10 °C for 16 h. The precipitate that formed was filtered off,
washed with PriOH and ether, and dried to give compound 2a,
EtOH—EtOAc), [α]D +30.5 (c 1, H2O); cf. Ref. 14: m.p.
203—204 °C, [α]D +31.5. 1H NMR, δ: 1.99 (s, 3 H, Me);
3.42—3.52 (m, 2 H, H(4), H(5)); 3.60 (t, 1 H, H(3), J2,3 = J3,4
=
9.0 Hz); 3.73 (dd, 1 H, H(6a), J5,6a = 5.0 Hz, J6a,6b = 12.5 Hz);
3.79—3.95 (m, 4 H); 5.05 (d, 1 H, H(1), J = 9.5 Hz).
(NꢀBromoacetylꢀβꢀDꢀglucopyranosylamine)uronamide (2g).
The reaction mixture was worked up as described for 2a. The
resulting precipitate was chromatographed on silica gel in acꢀ
etone. Fractions containing product 2g were combined and conꢀ
centrated. The precipitate that formed was filtered off, washed
with acetone and ether, and dried to give compound 2g, m.p.
20
m.p. 187—188 °C, [α]D –13.1 (c 1, H2O); cf. Ref. 10: m.p.
20
187—190 °C, [α]D –13.5 (c 1, H2O).
NꢀBromoacetylꢀβꢀDꢀgalactopyranosylamine (2b). The reacꢀ
tion mixture was filtered, diluted with MeOH (1.5 vol.), and
kept at –18 °C for 16 h. The precipitate that formed was filtered
off, washed with MeOH—anhydrous EtOH (1 : 1), acetone, and
ether, and dried to give compound 2b, m.p. 175—177 °C,
[α]D20 –11.2 (c 1, H2O); cf. Ref. 10: m.p. 192 °C, [α]D20 –13.0°
20
197—198 °C, [α]D –27.2 (c 1, H2O). Found (%): C, 31.02;
H, 4.25; Br, 25.15; N, 8.55. C8H13BrN2O6. Calculated (%):
C, 30.69; H, 4.18; Br, 25.52; N, 8.94. 1H NMR, δ: 3.48 (m, 1 H,
H(2)); 3.60 (m, 2 H, H(3), H(4)); 3.99 (m, 3 H, CH2, H(5));
5.05 (d, 1 H, H(1), J = 9.0 Hz).
1
(c 1, H2O). H NMR, δ: 3.58—3.83 (m, 5 H); 3.97 (br.s, 3 H,
NꢀBromoacetylꢀ4ꢀOꢀ(βꢀDꢀgalactopyranosyl)ꢀβꢀDꢀglucoꢀ
pyranosylamine (2h). The reaction mixture was filtered, diluted
with MeOH (1.3 vol.), and kept at –10 °C for 16 h. The precipiꢀ
tate that formed was filtered off, washed with cold MeOH and
ether, and dried to give compound 2h, m.p. 157—158 °C. Afꢀ
ter recrystallization from DMF—MeOH, m.p. 174—176 °C,
[α]D20 +2.5 (c 1, H2O). Found (%): C, 36.04; H, 5.30; Br, 16.90;
N, 3.18. C14H24BrNO11. Calculated (%): C, 36.38; H, 5.23;
Br, 17.29; N, 3.03. 1H NMR, δ: 3.42—3.55 (m, 2 H); 3.56—3.88
(m, 8 H); 3.89—3.98 (m, 2 H); 3.99 (s, 2 H, CH2); 4.48 (d, 1 H,
H(1) Gal, J = 7.5 Hz); 5.02 (d, 1 H, H(1) Glc, J = 9.5 Hz).
CH2, H(4)); 4.93 (d, 1 H, H(1), J = 9.0 Hz).
NꢀBromoacetylꢀβꢀDꢀmannopyranosylamine (2c). The reaction
mixture was worked up as described for 2a. The resulting precipiꢀ
tate was triturated with acetone. After the acetone was concenꢀ
trated, a small amount of product 2c precipitated. The residue
insoluble in acetone was dried and dissolved in MeOH at 20 °C.
The solution was concentrated to a small volume, the precipitate
that formed was filtered off and dissolved in hot MeOH, and the
solution was concentrated. The precipitate that formed was filꢀ
tered off, washed with acetone and ether, and dried to give

NꢀBromoacetylꢀβꢀglycopyranosylamines
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
713
NꢀBromoacetylꢀ6ꢀOꢀ(αꢀDꢀgalactopyranosyl)ꢀβꢀDꢀglucoꢀ
pyranosylamine (2i). The reaction mixture was worked up as
described for 2a. The resulting precipitate was chromatographed
on silica gel in acetone → acetone—MeOH (2 : 1). Fractions
containing product 2i were combined, concentrated to dryness,
gram for Support of the Leading Scientific Schools of the
Russian Federation, Grant NSh 1557.2003.3).
References
20
and dried to give amorphous compound 2i, [α]D +56.7
(c 1, H2O). Found (%): C, 36.02; H, 5.53; N, 2.87.
C14H24BrNO11. Calculated (%): C, 36.38; H, 5.23; N, 3.03.
1H NMR, δ: 3.43—3.96 (m, 12 H); 3.97 (s, 2 H, CH2); 4.97 (m,
2 H, H(1) Gal, H(1) Glc).
1. L. M. Likhosherstov, O. S. Novikova, V. A. Derevitskaya,
and N. K. Kochetkov, Izv. Akad. Nauk SSSR, Ser. Khim.,
1986, 1663 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1986, 35,
1512 (Engl. Transl.)].
NꢀBromoacetylꢀβꢀDꢀxylopyranosylamine (2j). The reaction
mixture was worked up as described for 2a. The resulting preꢀ
cipitate was chromatographed on silica gel in acetone. Fracꢀ
tions containing product 2j were combined and concentrated.
The precipitate that formed was filtered off, washed with
acetone—ether (1 : 2) and ether, and dried to give comꢀ
pound 2j. The mother liquor and the fractions containing chroꢀ
matographically more mobile substances than 2j were combined
and concentrated to dryness. The residue was dissolved in
MeOH—H2O—EtNPri2 (5.5 : 3.5 : 1, 15 vol. per gram of the
substance). The solution was kept at 20 °C for 1.5 h and then
diluted with MeOH—PriOH (1 : 1, 5 vol.). The solvent was
evaporated to dryness. The residue was chromatographed on
silica gel in acetone to give an additional amount of compound
2. L. M. Likhosherstov, O. S. Novikova, V. A. Derevitskaya,
and N. K. Kochetkov, Carbohydr. Res., 1986, 146, C1.
3. L. M. Likhosherstov, O. S. Novikova, V. N. Shibaev, and
N. K. Kochetkov, Izv. Akad. Nauk, Ser. Khim., 1996, 1848
[Russ. Chem. Bull., 1996, 45, 1760 (Engl. Transl.)].
4. L. M. Likhosherstov, O. S. Novikova, and V. N. Shibaev,
Dokl. Akad. Nauk, 2002, 383, 500 [Dokl. Chem., 2002,
383, 89].
5. L. M. Likhosherstov, O. S. Novikova, and V. N. Shibaev,
Dokl. Akad. Nauk, 2003, 389, 482 [Dokl. Chem., 2003,
389, 73].
6. L. M. Likhosherstov, O. S. Novikova, and V. N. Shibaev,
Izv. Akad. Nauk, Ser. Khim., 1998, 1244 [Russ. Chem. Bull.,
1998, 47, 1214 (Engl. Transl.)].
7. L. M. Likhosherstov, O. S. Novikova, and V. N. Shibaev,
Izv. Akad. Nauk, Ser. Khim., 1999, 1377 [Russ. Chem. Bull.,
1999, 48, 1365 (Engl. Transl.)].
8. L. M. Likhosherstov, O. S. Novikova, A. O. Zheltova, and
V. N. Shibaev, Izv. Akad. Nauk, Ser. Khim., 2000, 1461
[Russ. Chem. Bull., 2000, 49, 1454 (Engl. Transl.)].
9. E. W. Thomas, J. Med. Chem., 1970, 13, 755.
10. E. W. Thomas, Methods Enzymol., 1977, 46, 362.
11. T. S. Black, L. Kiss, D. Tull, and S. G. Withers, Carbohydr.
Res., 1993, 250, 195.
12. D. Macmillan, A. M. Daines, M. Bayrhuber, and S. L.
Flitsch, Org. Lett., 2002, 4, 1467.
13. L. A. Marcaurelle and C. R. Bertozzi, J. Am. Chem. Soc.,
2001, 123, 1587.
14. B. Paul, R. J. Bernacki, and W. Korytnyk, Carbohydr. Res.,
1980, 80, 99.
15. J. J. Malik and J. M. Risley, Magn. Reson. Chem.,
2001, 39, 98.
16. T. Kiss, A. Erdel, and L. Kiss, Arch. Biochem. Biophys.,
2002, 399, 188.
17. D. J. Vocaldo, J. Wicki, K. Rupitz, and S. G. Withers, Bioꢀ
chemistry, 2002, 41, 9736.
18. J. Chir, S. G. Withers, C. F. Wan, and Y. K. Li, Biochem. J.,
2002, 365, 857.
19. Z. Keresztessy, L. Kiss, and M. A. Hughes, Arch. Biochem.
Biophys., 1994, 315, 323.
20
2j (see Table 2), m.p. 155—156 °C (from acetone), [α]D +4.8
(c 1, H2O); cf. m.p. 150—151 °C (from MeOH),17 [α]D +6.4
(c 0.3, MeOH).16 1H NMR, δ: 3.36—3.53 (m, 3 H, H(2), H(3),
H(5a)); 3.63 (m, 1 H, H(4)); 3.93 (m, 1 H, H(5b)); 3.96 (s, 2 H,
CH2); 4.89 (d, 1 H, H(1), J = 9.0 Hz).
NꢀBromoacetylꢀ2ꢀdeoxyꢀβꢀDꢀarabinoꢀhexopyranosylamine
(2k). The reaction mixture was filtered and worked up as deꢀ
scribed for 2a (except that ether—light petroleum (1 : 1) was
used for precipitation). The resulting precipitate was chromatoꢀ
graphed on silica gel in acetone. Fractions containing product
2k were combined and concentrated to dryness. The residue was
dissolved in a minimum amount of MeOH and diluted with
ether (10 vol.). The precipitate that formed was filtered off,
washed with ether, and dried to give compound 2k. An addiꢀ
tional amount of amorphous compound 2k was isolated from
the mother liquor and other fractions upon Oꢀdeacylation as
described for 2j (see Table 2), [α]D20 –6.4 (c 1, H2O). Found (%):
C, 34.23; H, 5.22; N, 4.66. C8H14BrNO5. Calculated (%):
1
C, 33.82; H, 4.97; N, 4.93. H NMR, δ: 1.70 (m, 1 H, H(2a));
2.27 (m, 1 H, H(2e)); 3.36 (m, 1 H, H(4)); 3.51 (m, 1 H, H(5));
3.81 (m, 2 H, H(3), H(6a)); 3.94 (m, 1 H, H(6b)); 3.99 (s, 2 H,
CH2); 5.23 (dd, 1 H, H(1), J1,2e = 2.5 Hz, J1,2a = 10.5 Hz).
NꢀBromoacetylꢀ2ꢀdeoxyꢀβꢀDꢀlyxoꢀhexopyranosylamine (2l)
was obtained as described above for 2k. After column chromaꢀ
tography, the fractions containing product 2l were combined
and concentrated. The precipitate that formed was filtered
off, washed with cold acetone and ether, and dried to give
20. E. A. Hassoun, D. Bagchi, V. F. Roche, and S. J. Stohs, J.
Appl. Toxicol., 1996, 16, 49.
20
compound 2l, m.p. 159—161 °C, [α]D –16.2 (c 1, H2O).
Found (%): C, 33.98; H, 5.08; N, 4.56. C8H14BrNO5. Calcuꢀ
lated (%): C, 33.82; H, 4.97; N, 4.93. 1H NMR, δ: 1.84 (m, 1 H,
H(2a)); 1.99 (m, 1 H, H(2e)); 3.71 (m, 1 H, H(4)); 3.78 (m, 2 H);
21. M. F. Ansell and R. H. Gigg, in Rodd´s Chemistry of Carbon
Compounds, Ed. S. Coffey, Elsevier, Amsterdam, 1965,
1C, 156.
3.87 (br.s, 1 H); 3.98 (m, 3 H); 5.16 (dd, 1 H, H(1), J1,2e
2.5 Hz, J1,2a = 10.5 Hz).
=
22. A. C. Rottinger and F. Wenzel, Monatsh. Chem., 1913,
34, 1867.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 01ꢀ03ꢀ
33267a) and the President of the Russian Federation (Proꢀ
Received October 7, 2003;
in revised form November 19, 2003