A synthesis of heteroaromatic S- and N-β-glycosides of N-acetylglucosamine under phase-transfer conditions

Article abstract of DOI:10.1007/s11171-005-0063-z

The use of crown ethers for a phase transfer-catalyzed synthesis of heteroaromatic glycosides of N-acetylglucosamine was studied. The solid-liquid system and catalysis by 15-crown-5 were found to provide for both the 100% conversion of α-D-glucosaminyl ch

Full text of DOI:10.1007/s11171-005-0063-z

Russian Journal of Bioorganic Chemistry, Vol. 31, No. 5, 2005, pp. 460–466. Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 5, 2005, pp. 511–518.
Original Russian Text Copyright © 2005 by Kur’yanov, Chupakhina, Zemlyakov, Chirva, Shishkin, Shishkina, Kotlyar, Kamalov.
A Synthesis of Heteroaromatic S- and N-b-Glycosides
of N-Acetylglucosamine under Phase-Transfer Conditions
1
V. O. Kur’yanov*, T. A. Chupakhina*, A. E. Zemlyakov*, V. Ya. Chirva*, O. V. Shishkin**,
S. V. Shishkina**, S. A. Kotlyar***, and G. L. Kamalov***
* Vernadsky Tauric National University, ul. Yaltinskaya 4, Simferopol, 95007 Ukraine
** Institute of Scintillation Materials, Institute of Single Crystals Scientific Research Center,
National Academy of Sciences, Ukraine
*** Bogatsky Physicochemical Institute, National Academy of Sciences, Ukraine
Received December 7, 2004; in final form, March 21, 2005
Abstract—The use of crown ethers for a phase transfer-catalyzed synthesis of heteroaromatic glycosides of N-
acetylglucosamine was studied. The solid–liquid system and catalysis by 15-crown-5 were found to provide for
both the 100% conversion of α-D-glucosaminyl chloride peracetate and a high reaction rate. The interaction of
α-D-glucosaminyl chloride peracetate and oxadiazole and triazole mercapto derivatives capable of thiol–thione
tautomerism carried out at room temperature in acetonitrile in the presence of anhydrous potassium carbonate
and crown ethers was shown to lead to both S- and N-glucosides. The structures of the compounds synthesized
were confirmed by X-ray analysis and 13ë and 1H NMR spectroscopy.
Key words: crown ethers, glycosylation, heteroaromatic glycosides, phase transfer catalysis, X-ray analysis
1
INTRODUCTION
under the PTC conditions, only few examples have
been known (cf., e.g., [17–21].
A high efficiency of phase transfer catalysis in the
presence of quaternary ammonium salts and crown
ethers exemplified by numerous examples of O-, S-,
and N-alkylation of alcohols, phenols, thiols, and nitro-
gen-containing heterocyclic systems [1, 2] was con-
firmed by a considerable number of examples in carbo-
The goal of this work is the search for new effective
synthetic approaches to the formation of S- or N-glyco-
side bonds using CE as phase transfer catalysts, which
would result in the synthesis of new glucosaminides
with a potential biological activity.
2
hydrate chemistry [3–9]. The reactions at the anomeric
carbon atoms of glycosyl halogenides of both neutral
and amino sugars are of a particular interest, because
modifications of the monosaccharide glycoside centers
provide not only the introduction of protective groups
at the carbohydrate C1 atom, but also the preparation of
biologically diverse O-, S-, and N-glycosides, including
the derivatives of physiologically important natural
compounds [10–21]. However, the use of PTC for gly-
coside synthesis is restricted to classical examples of
the preparation of alkyl O-β-D-glucopyranosides in the
presence of silver nitrate and various CEs as catalysts
[6, 9]. The synthesis of aryl O-β-D-gluco- and galacto-
pyranosides and aryl O-β-D-glucosaminides from the
corresponding acetobromosugars and 2-acetamido-
3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl chlo-
ride in a biphasic liquid–liquid system with alkali as a
base and quaternary ammonium salts as catalysts [4, 5,
7, 8] is limited to the glycosylation of aromatic alkali-
stable compounds. As to the synthesis of N-glycosides
RESULTS AND DISCUSSION
We had earlier shown [22, 23] that the use of 20 mol %
(per substrate) of catalysts (15K5 or aromatic CEs) in
the presence of K2CO3 suspension in dry acetonitrile
ensures a smooth phase transfer glycosylation of phe-
nols, synthetic coumarine analogues, and chromones
with 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glu-
copyranosyl chloride (I) (the yields of O-glycosides
achieve 43–86% with 100% substrate conversion). We
discuss here the fundamental possibility of glycosyla-
tion and the specific features of interaction of chloride
(I) with heteroaromatic compounds (II)–(V) under PTC
conditions. A distinguishing feature of the heterocyclic
systems under consideration is their ability to tauto-
meric transformations due to which the glycosylation
direction may differ in dependence on the reaction con-
ditions. Proper examples are well known (cf. [15]).
The consideration of equilibrium inherent for com-
pounds (II)–(V) suggests that the reaction could pro-
ceed at one of two nucleophilic centers to give either S-
or N-glycoside or a mixture of both.
1
Corresponding author: fax: (0652) 23-2310; phone: (0652) 23-
3885; e-mail: vladimir@tnu.crimea.ua
2
Abbreviations: 15C5, 15-crown-5; 18C6, 18-crown-6; CE, crown
ether; and PTC, phase transfer catalysis.
1068-1620/05/3105-0460 © 2005 Pleiades Publishing, Inc.

A SYNTHESIS OF HETEROAROMATIC S- AND N-β-GLYCOSIDES
461
H
OAc
O
N N
O
N N
O
H
AcO
AcO
N N
O
N N
O
SH
SH
S
S
AcHN
SH
S
Cl
(I)
(II)
(III)
H
H
N N
N
N N
N
N N
N N
SH
S
Cl
Cl
N
N
Me
Me
(IV)
(V)
Me
Me
A preliminary experiment carried out in the absence time and product yields. As follows from the data in
of phase transfer catalysts demonstrated that the major Figs. 1 and 2, this substitution offers no advantages nei-
product in acetonitrile–anhydrous potassium carbonate ther in the process time nor in total yields of target gly-
was oxazoline (XIV) (TLC monitoring). The total con- cosides.
version of the substrate was not achieved, and the target
1H NMR (Table 1 and Fig. 3) and 13C NMR spec-
glycosides were formed in trace amounts.
troscopy (see the Experimental section), X-ray analysis
The attempts to glycosylate thiols (II)–(V) in the
presence of triethylamine (as described in [24]) also
failed. No complete conversion of substrate (I) was
observed in any of the cases; along with the target prod-
ucts (TLC monitoring), oxazoline (XIV) was formed.
The reactions of α-chloride (I) with thiol–thione
tautomers, namely, 5-benzyl-1,3,4-oxadiazole-2-thiol
(II), 5-phenyl-1,3,4-oxadiazole-2-thiol (III), 4-methyl-
1,2,4-triazole-3-thiol (IV), and 5-(4-chlorophenyl)-4-
ethyl-1,2,4-triazole-3-thiol (V), at stoichiometric ratios
described in [22, 23] yielded two products in each case:
(VI) and (VII), (VIII) and (IX), (X) and (XI), and
(XII) and (XIII), respectively. Note that, in all the
cases, chloride (I) was completely converted.
(Fig. 4), and the S-β- to N-β glycoside rearrangement
catalyzed by mercury(II) bromide [15] were used for
the elucidation of the glycoside bond structure and
nature in (VI)–(XIII), which supposed to be pairs of S-
β- and N-β-glucosaminides. The 1H NMR spectral pat-
terns of the glycoside pairs (VI)–(XIII) studied
(Table 1) showed a significant downfield shift of the
anomeric proton resonances of N-β-glycosides (VII),
(IX), ((XI), and (XIII) in comparison with the H1 dou-
blets of S-β-D-glucosaminides (VI), (VIII), (X), and
(XII). The coupling constants of N-β- and S-β-glyco-
sides were 9.6–9.9 and 10.5–10.8 Hz, respectively
(Table 1), which corresponds to the published data [4,
24–27]. The chemical shifts of skeletal protons of gly-
coside residues of S- and N-glycosides significantly dif-
fered from one another and could therefore serve as
their characteristic feature (Fig. 3).
We made a number of syntheses in which 18C6 was
substituted for 15C5 in order to reveal the effect of the
macrocycle size and dentation on the glycosylation
Yield, %
100
Time, h
6
90
15C5 18C6
15C5 18C6
80
70
60
50
5
4
3
2
1
40
30
20
10
0
0
(VI) + (VII) (VIII) + (IX) (X) + (XI) (XII) + (XIII)
(VI) + (VII) (VIII) + (IX) (X) + (XI) (XII) + (XIII)
Fig. 2. Total yield of S- and N-β-glycosides in the presence
of 15C5 and 18C6 crown ethers at 100% conversion of sub-
strate (I).
Fig. 1. The formation time of glycoside in the presence of
15C5 and 18C6 crown ethers at 100% conversion of sub-
strate (I).
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 31 No. 5 2005

462
KUR’YANOV et al.
N
N N
OAc
6
2'
S
O
N
S
4
5
S
O 1 R
O
O
AcO
AcO
N
R =
2'
N
2 NHAc
3
(VI)
(VII)
(VIII)
Me
S
S
N N
N
O
N
S
N
N
N
OAc
O
N
Me
AcO
AcO
(IX)
(X)
(XI)
S
Me
N
O
N N
N
N
S
N
Cl
N
(XIV)
Cl
Me
(XII)
(XIII)
Thioglycosides (VI), (VIII), (X), and (XII) were and (XIII). For a more accurate assignment of (VI) and
(VII) to S- or N-glycosides, 13C NMR spectra were reg-
istered (see the Experimental section). A downfield
shift of the resonance of the anomeric carbon atom was
isomerized in the presence of mercury(II) bromide [15]
into the compounds whose chromatographic mobility,
1
physicochemical characteristics, and H NMR data
agreed with those of N-β-glycosides (VII), (IX), (XI), observed in the 13C NMP spectrum of N-glycoside
1
Table 1. H NMR spectra of (VI)–(XIII)*
Group or atom
(VI)
(VII)
(VIII)
(IX)
(X)
(XI)
(XII)
(XIII)
H1 (J1,2)
5.44 d
(10.8)
5.95 d
(9.6)
5.57 d
(10.5)
6.08 d
(9.6)
5.11 d
(10.5)
6.15 d
(9.9)
5.27 d
(10.8)
6.22 d
(9.6)
H2 (J2,3)
H3 (J3,4)
H4 (J4,5)
4.07 m
(9.6)
4.33 ddd
(9.6)
4.11 m
4.36 ddd
(9.6)
3.92 ddd
(10)
4.45 ddd
(9.6)
4.08 m
4.50 ddd
(10)
5.19 dd
(9.6)
5.38 dd
(10)
5.23 dd
(9.3)
5.48 dd
(9.7)
5.13 dd
(9.6)
5.39 dd
(9.9)
5.17 dd
(9.9)
5.43 dd
(9.9)
4.88 dd
(9.6)
4.94 dd
(10)
4.92 dd
(9.6)
4.99 dd
(9.6)
4.83 dd
(9.9)
4.93 dd
(9.9)
4.87 dd
(9.9)
4.95 dd
(9.9)
H5 (J5,6a, J5,6b
)
3.91 m
4.14 m
4.11 m
(2.1, 5.1)
4.20 ddd
(2.1, 5.1)
3.81 ddd
(2.4, 5.4)
4.01 m
(2.1, 5.1)
3.85 ddd
(2.1, 5.4)
4.07 m
(2.1, 5.1)
H6 (Jgem
)
3.91 m,
4.07 m
4.21 m
4.00 dd,
4.16 dd
(12.0)
4.07 dd,
4.26 dd
(12.0)
3.96 dd,
4.09 dd
(12.5)
4.05 dd,
4.46 dd
(12.6)
4.08 m
4.10 dd,
4.25 dd
(12.5)
NHAc
OAc
1.78 s
1.67 s
1.83 s
1.67 s
1.83 s
1.62 s
1.84 s
1.64 s
1.94 s,
1.95 s,
1.98 s
1.94 s,
2.00 s
1.95 s,
1.99 s
1.96 s,
2.01 s
1.93 s,
1.96 s,
1.97 s
1.93 s,
1.98 s,
1.99 s
1.90 s,
1.94 s,
1.97 s
1.94 s,
1.99 s,
2.00 s
NH (JNH,2
)
8.18 d
(9.3)
8.03 d
(8.7)
8.27 d
(9.3)
8.05d
(8.4)
8.23 d
(9.0)
7.95 d
(9.0)
8.28 d
(9.3)
7.99 d
(8.7)
Alk
4.14 s,
4.29 s
4.17 s,
4.20 s
–
–
3.62 s
3.47 s
1.62 t,
4.08 m
1.14 t,
4.07 m
CHarom
7.33 m
7.33 m
7.65 m
7.65 m,
7.91 d
8.67 s
8.52 s
7.65 d,
7.72 d
7.69 d,
7.76 d
* Working frequency of 300 MHz; DMSO-d as a solvent.
6
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 31 No. 5 2005

A SYNTHESIS OF HETEROAROMATIC S- AND N-β-GLYCOSIDES
463
(VI)
5.5
5.0
4.5
4.0
(VII)
6.0
5.5
5.0
ppm
4.5
4.0
1
Fig. 3. The resonance region of skeletal protons in H NMR spectra of (VI) and (VII).
C13
C11
C12
O6
C14
C10
N3
C15
O1
C6
O2
N2
C17
C1
C9
C5
C16
S1
O5
C2
N1
C4
O3
C3
C7
O4
C8
Fig. 4. Molecular structure of N-β-glycoside (XV).
(VII) (δ 85.03 ppm; compare with δ 84.09 ppm for S- lower value of the partial negative charge on this atom
calculated using the standard programs, e.g., those in
ChemOffice Ultra 8.0.
glycoside) whose C1 is linked to a more electronegative
nitrogen atom. Chemical shifts of the C2' aglycone
atoms more substantially differ. The resonance of this
carbon atom in N-glycoside (VII) undergo a diamag-
netic shift in comparison with that of S-glycoside (VI)
The final proof of the correctness of assigned struc-
tures was obtained by the X-ray analysis of deacety-
lated derivative (XV) (Fig. 4). Atomic coordinates,
(167.44 ppm versus 178.70 ppm), which correlates to a bond lengths, and values of torsion angles in triol (XV)
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 31 No. 5 2005

464
KUR’YANOV et al.
Table 2. The coordinates (×104) and equivalent isotropic
temperature parameters (×103, Å2) of atoms in (XV).
are shown in Tables 2–4. The six-membered pyranose
cycle has the C1 conformation in the crystal (chair,
4
folding parameters: S = 1.18, Θ = 7.4°, Ψ = 16.7° [28]).
All the substituents are equatorial in the cycle. The
bond lengths in the aglycone agree with the published
data [29]. Noteworthy is the difference between the
ësp3–O bonds in the carbohydrate residue (O1–C5
1.441(3) and O1–C1 1.406(4) Å), which has been
described for relative compounds (e.g., see [30]) and is
a consequence of anomeric effect.
Thus, the whole information obtained unequivo-
cally proves the chemical structures of S-β- and N-β-
glycosides (VI)–(XIII). To conclude, the method we
have suggested for the crown ether-catalyzed glycosy-
lation of phenols in the phase transfer solid–liquid sys-
tem turned out to be also effective for β-glucosamida-
tion of aromatic heterocycles both at the exocyclic sul-
fur atom and endocyclic nitrogen atom; it helps obtain
heteroaromatic S- and N-β-glycosides of N-acetylglu-
cosamine.
Atom
x
y
z
Ueq
S1
8621(1)
9275(3)
6536(3)
5623(3)
4912(3)
6954(3)
9260(3)
7893(3)
5531(3)
1914(3)
6590(4)
7518(4)
7364(4)
5563(4)
4883(4)
3119(4)
9959(4)
11637(4)
7374(4)
5901(4)
1690(1)
–18(1)
27(1)
17(1)
15(1)
16(1)
15(1)
21(1)
21(1)
22(1)
25(1)
25(1)
14(1)
13(1)
15(1)
17(1)
14(1)
21(1)
17(1)
25(1)
17(1)
19(1)
25(1)
22(1)
23(1)
28(1)
29(1)
36(1)
34(1)
N1
N2
N3
O1
O2
O3
O4
O5
O6
C1
1889(2) –1798(1)
1124(2) –974(1)
102(2) –1189(1)
2686(2) –1400(1)
–386(2)
–328(1)
–246(2) –1861(1)
3051(2) –2932(1)
5080(2) –2564(1)
3787(2) –1989(1)
2302(3) –1312(1)
2131(3) –1929(1)
3329(3) –2320(1)
3831(3) –2326(1)
3925(3) –1672(1)
4446(3) –1628(1)
747(3) –1707(1)
787(3) –1387(2)
C2
C3
C4
C5
EXPERIMENTAL
C6
Melting points were measured on a PTP device.
C7
Optical rotations were registered at 20–22°ë on a Pola-
C8
1
mat-A polarimeter (at the wavelength λ 546 nm). H
C9
852(3)
–452(1)
–790(1)
–777(2)
–771(2)
–327(2)
–327(2)
–763(2)
NMR spectra were obtained in DMSO-d6 on a Varian
VXR-300 spectrometer (300 MHz) with Me4Si as an
C10
C11
C12
C13
C14
C15
C16
C17
–761(3)
13
5213(4) –2067(3)
6582(4) –3046(3)
6585(4) –3989(3)
7812(5) –4902(3)
9094(5) –4878(3)
internal standard. C NMR spectra were registered in
ëDël3 on a Varian Mercury-400 spectrometer
1
(100 MHz). The assignment of H NMR resonances
was achieved using the method of double homonuclear
resonance.
X-ray analysis. The rhombic-shaped crystals of
compound (XV), ë17ç21N3O6S, have at −109°ë the
following parameters: a = 7.942(2), b = 10.603(3), c =
21.721(5) Å, V = 1829.1(8) Å3, Mr = 395.43, Z = 4, the
9100(5) –3933(3) –1203(2)
7860(5) –3016(3) –1207(2)
spatial group P212121, dcalc = 1.436 g/cm3, µ(MoKα) =
Table 3. Bond lengths (Å) in (XV).
0.217 mm–1, and F(000) = 832. The parameters of the
elementary cell and the intensity of 2399 independent
images were measured on an automatic four-round Sie-
mens P3/PC diffractometer (MoKα, graphite mono-
chromator, θ/2θ scanning, 2θm‡ı = 55°). The structure
was calculated by the direct method using the
SHELXTL program complex [31]. The positions of
hydrogen atoms were obtained by the differential cal-
culations of electron density and adjusted using the
“raider” model with a free Uiso. The structure was
refined according to the squares of structural ampli-
tudes using a full-matrix method of root least squares
and anisotropic approximation for nonhydrogen atoms
to wR2 = 0.108 for 2354 reflects (R1 = 0.042 for 2082
reflects with F > 4σ(F), S = 1.076).
S1–C9
1.630(3)
1.447(4)
1.385(3)
1.279(4)
1.442(3)
1.380(3)
1.426(3)
1.421(4)
1.533(4)
1.523(4)
1.504(4)
1.504(5)
1.389(5)
1.391(5)
1.383(5)
N1–C7
1.342(4)
1.348(4)
1.449(3)
1.406(4)
1.365(4)
1.237(4)
1.422(4)
1.539(4)
1.526(4)
1.509(4)
1.489(4)
1.389(4)
1.373(5)
1.385(5)
N1–C2
N2–N3
N3–C10
O1–C5
O2–C9
O4–C3
O6–C6
C2–C3
N2–C9
N2–C1
O1–C1
O2–C10
O3–C7
O5–C4
C1–C2
C3–C4
C4–C5
C5–C6
C7–C8
C10–C11
C12–C13
C13–C14
C15–C16
C11–C12
C12–C17
C14–C15
C16–C17
TLC was carried out on Sorbfil-AFB-UV plates
(“Sorbpolymer”, Russia). Column chromatography
was performed on Kieselgel 60 (0.063–0.200 mm,
Merck). The substance spots were detected by carbon-
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A SYNTHESIS OF HETEROAROMATIC S- AND N-β-GLYCOSIDES
465
Table 4. Valence angles (degrees) in (XV)
ization or in iodine vapor. For the plate development,
the following elution systems were used: (A) 15 : 1 : 1
ethyl acetate–chloroform–ethanol, (B) 10 : 1 benzene–
ethanol, (C) 3 : 1 : 1 n-butanol–acetic acid–water. The
data of elemental analyses of the compounds synthe-
sized agree with the calculated values.
C7–N1–C2
C9–N2–C1
C10–N3–N2
C10–O2–C9
O1–C1–C2
N1–C2–C3
C3–C2–C1
O4–C3–C2
O5–C4–C5
C5–C4–C3
O1–C5–C4
O6–C6–C5
O3–C7–C8
N2–C9–O2
O2–C9–S1
N3–C10–C11
125.3(3)
126.6(2)
103.9(2)
106.4(2)
111.7(2)
109.4(2)
110.2(2)
108.8(2)
105.7(2)
110.3(2)
108.5(2)
114.3(2)
123.1(3)
104.3(3)
123.6(2)
127.9(3)
C9–N2–N3
N3–N2–C1
C1–O1–C5
O1–C1–N2
N2–C1–C2
N1–C2–C1
O4–C3–C4
C4–C3–C2
O5–C4–C3
O1–C5–C6
C6–C5–C4
O3–C7–N1
N1–C7–C8
N2–C9–S1
N3–C10–O2
O2–C10–C11
112.0(2)
121.3(2)
109.5(2)
106.8(2)
110.7(2)
108.1(2)
109.9(2)
111.6(2)
110.2(3)
108.8(2)
114.4(2)
123.2(3)
113.6(3)
132.1(2)
113.3(3)
118.8(3)
General glycosylation procedure. Equimolar
amounts of the corresponding heteroaromatic com-
pound, finely ground anhydrous K2CO3, and 15C5
(20 mol % per substrate, 98% according to GLC,
Bogatskii Physicochemical Institute, Odessa) were
added to a solution of 2-acetamido-3,4,6-tri-O-acetyl-
2-deoxy-α-D-glucopyranosyl chloride (I) [32] in ace-
tonitrile (30 ml/g), and the mixture was stirred at room
temperature until the complete conversion of the glyc-
osyl donor (TLC monitoring in systems A and B). The
solid phase was filtered off, and acetonitrile was evapo-
rated at a reduced pressure. The residue was crystal-
lized from isopropyl alcohol, the precipitate was fil-
tered, and the mother liquor after was evaporated and
chromatographed on a silica gel column.
C10–C11–C12 112.1(3)
C13–C12–C11 120.3(3)
C14–C13–C12 120.6(3)
C16–C15–C14 119.1(3)
C16–C17–C12 120.0(3)
C13–C12–C17 119.2(3)
C17–C12–C11 120.5(3)
C13–C14–C15 120.4(3)
C17–C16–C15 120.7(3)
3-N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-
D-glucopyranosyl)-5-benzyl-1,3,4-oxadiazole-2(3H)-
thione (VII) and 2-(2-acetamido-3,4,6-tri-O-acetyl-
2-deoxy-b-D-glucopyranosylthio)-5-benzyl-1,3,4-
oxadiazole (VI). The interaction of oxadiazole (II)
(0.625 g, 3.26 mmol) and chloride (I) (1.19 g,
3.26 mmol) followed by crystallization resulted in gly-
coside (VII); yield 0.287 g (17%); mp 162–165°C
(degr.); [α]546 +31° (c 0.67; chloroform); 13C NMR:
20.95, 21.04, 21.08, 23.40 (4 CH3CO), 32.18 (CH2Ph),
53.22 (C2), 62.00 (C6), 68.17 (C4), 73.66 (C3), 76.62
(C5), 85.03 (C1), 128.13, 129.22, 129.35, and 133.52
(C6H5), 163.00 (C5'), 167.44 (C2'), 169.61, 170.89,
171.04, and 171.38 (COCH3). Glycoside (VI) was
obtained after chromatography on a column eluted with
a gradient benzene to 25 : 1 benzene–propan-2-ol; yield
0.338 g (20%); mp 94–98°C (degr.), [α]546 –13° (c 0.67
1-N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-
D-glucopyranosyl)-2,4-dihydro-4-methyl-1,2,4-tri-
azole-3-thione (XI) and 3-(2-acetamido-3,4,6-tri-O-
acetyl-2-deoxy-b-D-glucopyranosylthio)-4-methyl-
1,2,4-triazole (X). The interaction of triazole (IV)
(0.221 g, 1.91 mmol) and chloride (I) (0.7 g,
1.91 mmol) followed by crystallization resulted in gly-
coside (XI); yield 0.25 g (29%); mp 247–250°ë
(degr.); [α]546 +50° (c 1.0; chloroform). Glycoside (X);
yield 0.26 g (30%) was obtained after chromatography
on a column eluted with a benzene to 15 : 1 benzene–
isopropanol; mp 144–148°ë, [α]546 –12° (c 1.0; chloro-
form).
1.0; chloroform); 13C NMR: 21.02, 21.13, and 23.51
(4 CH3CO); 32.49 (CH2Ph), 52.62 (C2), 62.19 (C6),
68.04 (C4), 73.10 (C3), 75.20 (C5), 84.09 (C1), 128.30,
129.38, 129.43, 129.49, and 132.32 (C6H5), 161.75
(C5'), 169.62, 170.39, 171.02, and 171.55 (COCH3),
178.70 (C2').
1-N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-D-
glucopyranosyl)-2,4-dihydro-5-(4-chlorophenyl)-4-
ethyl-1,2,4-triazole-3-thione (XIII) and 3-(2-acet-
amido-3,4,6-tri-O-acetyl-2-deoxy-b-D-glucopyranos-
ylthio)-5-(4-chlorophenyl)-4-ethyl-1,2,4-triazole (XII).
The interaction of triazole (V) (0.522 g, 2.60 mmol)
and chloride (I) (0.95 g, 2.60 mmol) followed by crys-
tallization resulted in glycoside (XIII); yield 0.50 g
(34%); mp 238–242°ë (degr.); [α]546 –27° (c 0.67;
chloroform). Glycoside (XII) was obtained after a
chromatography on a column eluted with a benzene to
20 : 1 benzene–isopropanol; an amorphous compound;
yield 0.385 g (26%); [α]546 +25° (c 1.0; chloroform).
3-N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-D-
glucopyranosyl)-5-phenyl-1,3,4-oxadiazole-2(3H)-
thione (IX) and 2-(2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy-b-D-glucopyranosylthio)-5-phenyl-1,3,4-oxa-
diazole (VIII). The interaction of oxadiazole (III)
(0.317 g, 1.78 mmol) and chloride (I) (0.65 g,
1.78 mmol) followed by crystallization resulted in gly-
coside (IX); yield 0.198 g (22%); mp 257–260°ë
(degr.); [α]546 –39° (c 1.0; chloroform). Glycoside
(VIII), was obtained after chromatography on a col-
umn eluted with a benzene to 25 : 1 benzene–isopro-
panol gradient; yield 0.338 g (20%); mp 244–245°ë
(degr.), [α]546 –18° (c 1.0; chloroform).
3-N-(2-Acetamido-2-deoxy-b-D-glucopyranosyl)-
5-benzyl-1,3,4-oxadiazole-2(3H)-thione (XV).
A
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 31 No. 5 2005

466
KUR’YANOV et al.
11. Liu Fei and Austin, D.J., J. Org. Chem., 2001, no. 66,
solution of 0.1 N sodium methylate in methanol
(0.05 ml) was added to a solution of peracetate (VI)
(150 mg) in absolute methanol (5 ml). After the reac-
tion was completed (TLC monitoring, systems A and
B), it was treated with a cation exchange resin KU-2
(ç+ form). The resin was filtered off, the filtrate was
evaporated to dryness, and the residue of triol was crys-
tallized from water to give glycoside (XV); yield
103 mg (90%); mp 159–161°ë (degr.); [α]546 +42° (c
1.0; DMSO).
General procedure for the S-b to N-b glycoside
rearrangement [15]. Mercury(II) bromide was sus-
pended in a calculated amount of xylene (100 ml per
1.25 mmol of bromide), one quarter of xylene volume
was evaporated at a reduced pressure, the correspond-
ing S-β glucosaminide (the molar ratio of S-β-glucoside
to bromide 1 : 5) was added, and the mixture was
refluxed until a complete conversion to N-β-glycosides
(TLC monitoring). Xylene was evaporated, the residue
was dissolved in chloroform, and the organic layer was
successively washed with 30% potassium iodide, 5%
sodium carbonate, and water. The organic layer was
separated, dried with anhydrous sodium sulfate, and
evaporated. The target compounds were isolated by
crystallization from isopropanol.
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