Preparation of diamino pseudodisaccharide derivatives from 1,6-anhydro-β-d-hexopyranoses via aziridine-ring cleavage

Article abstract of DOI:10.1016/j.carres.2006.11.028

Twelve positional isomers of diamino pseudodisaccharide derivatives with gluco-gluco configuration have been prepared using aziridine-ring cleavage of epimino derivatives of 1,6-anhydro-β-d-hexopyranoses of the d-allo, d-manno, and d-galacto configuration

Full text of DOI:10.1016/j.carres.2006.11.028

Carbohydrate Research 342 (2007) 147–153
Preparation of diamino pseudodisaccharide derivatives from
1,6-anhydro-b-D-hexopyranoses via aziridine-ring cleavage
a,
b
*
ˇ´
ˇ
ˇˇ´
´
Jirı Kroutil and Milos Budesınsky
aDepartment of Organic and Nuclear Chemistry, Charles University in Prague, 128 43 Prague 2, Czech Republic
bInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
Received 20 June 2006; received in revised form 13 November 2006; accepted 29 November 2006
Available online 6 December 2006
Abstract—Twelve positional isomers of diamino pseudodisaccharide derivatives with gluco–gluco configuration have been prepared
using aziridine-ring cleavage of epimino derivatives of 1,6-anhydro-b-D-hexopyranoses of the D-allo, D-manno, and D-galacto config-
uration by 2-, 3-, and 4-amino derivatives of 1,6-anhydro-b-D-glucopyranose. The N-substitution of the aziridine ring by a 2-nitro-
benzenesulfonyl group and ionic-liquid solvent (N-methylpyridinium tosylate) was used to obtain cleavage products in high yield (64–
93%). The cleavage reactions proceeded according to the Furst–Plattner rule and only trans-diaxial stereoisomers were formed.
¨
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Ring-opening reactions; Stereospecific synthesis; Aziridines; Nitrobenzenesulfonamides; Ionic-liquid solvent
1. Introduction
linkages, such as nucleophilic substitution, small-ring
opening, or addition to an activated double bond,
applied to pseudodisaccharide synthesis mostly result
in mixtures of products and tedious separation has to
be performed.
The term pseudodisaccharide covers a wide range of
compounds, which structurally resemble common disac-
charides. One of the structural type of pseudodisaccha-
rides has two coupled monosaccharide units in which
the linkage (usually etheric, thio, or imino linkage) does
not interconnect anomeric carbon atoms. These com-
pounds cannot be hydrolyzed to monosaccharides by
enzymatic action and thus can act as enzyme inhibitors
(glycosidases and glycosyltransferases). There are some
examples in the literature of the preparation of isomeric
pseudodisaccharides for studies of their use as glycosi-
dase inhibitors, such as those based on D-glucose1 that
inhibit threhalase and others, which inhibit glucosidase,2
mannosidase,3 and galactosidase.4,5 Whereas the diver-
sity of pseudodisaccharide molecules is great due to
positional and configurational isomerism, synthetic
methods for their preparation are rather limited because
glycosidation procedures cannot be applied. General
methods for the formation of etheric, thio, or imino
Recently, we published a series of papers6,12,21,22 deal-
ing with reactivity and stereoselectivity in nucleophilic
cleavage reactions of sugar aziridines based on 1,6-an-
hydrohexoses. We elaborated reaction conditions for
aziridine-ring cleavage to obtain only one isomer of
the cleavage product with well-defined and predictable
stereochemistry. By the aziridine-ring-opening protocol
applied to sugar aziridines and sugar nucleophiles, a
structural series of pseudodisaccharides could be pro-
duced. In this paper, we use cleavage reactions of four
1,6-anhydro-epimino-hexoses with three amino-1,6-
anhydro-glucoses for the preparation of 12 isomeric
pseudodisaccharide derivatives.
2. Results and discussion
The starting nosylepimines 1–4 (Fig. 1), were prepared
from suitably substituted 1,6-anhydrohexoses (possess-
ing OTs, N3, and OBn groups on the tetrahydropyran
*
Corresponding author. Fax: +420 221951326; e-mail addresses:
kroutil@natur.cuni.cz; mbudes@uochb.cas.cz
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.11.028

148
J. Kroutil, M. Budeˇsˇı´nsky´ / Carbohydrate Research 342 (2007) 147–153
O
charides 8–19 were obtained in the yields 93%, 76%, 86%,
75%, 66%, 80%, 64%, 82%, 67%, 82%, 68%, and 89% (see
Scheme 2).
O
O
O
Ns
O
O
O
O
N
NNs
The cleavage reactions produced the isomers with
trans-diaxial disposition of the introduced amino group
and the sulfonamido group only; no diequatorial iso-
mers were detected in the reaction mixtures. Therefore
we can conclude that in all cases, the cleavage of the azi-
ridine ring proceeded stereochemically in accordance
BnO
BnO
NsN
OBn
N
Ns
OBn
2
3
4
1
Figure 1. Epimino derivatives of 1,6-anhydro-b-D-hexopyranoses 1–4
used for aziridine-ring cleavage (Ns = 2-nitrobenzenesulfonyl).
with the Furst–Plattner rule13 prediction (trans-diaxial
¨
aziridine-ring cleavage).
ring) by sodium borohydride (compounds 2, 3, and 4—
Refs. 6 and 7) or lithium aluminum hydride (compound
1—Refs. 6 and 8) reduction. Subsequent N-nosylation
using 2-nitrobenzenesulfonyl chloride in a triethyl-
amine–tetrahydrofuran mixture at À40 ꢁC afforded6,7
the mentioned N-nosylepimino derivatives 1–4.
The structure of derivatives 8–19 was determined by
1H and 13C NMR spectroscopies (for NMR data—see
Tables 1–3). Structure assignment of protons and car-
bons inside each 1,6-anhydrohexose unit was achieved
R1 =
R2 =
R3
=
O
O
O
The sugar nucleophiles, 2-amino-1,6-anhydro-4-O-
benzyl-2-deoxy- and 4-amino-1,6-anhydro-2-O-benzyl-
4-deoxy-b-D-glucopyranose (5 and 7), were prepared by
reduction of the corresponding azido derivatives by
NaBH4 in THF/MeOH. 3-Amino-1,6-anhydro-3-
deoxy-b-D-glucopyranose (6) was prepared by hydro-
genation of the corresponding azido derivative over
10% palladium-on-charcoal catalyst (Scheme 1). In com-
parison with previous preparation of derivatives 5–7
(compound 5—Ref. 9, compound 6—Ref. 10, compound
7—Ref. 11), our preparative approach gave better yields.
The aziridine-ring cleavage of molten reactants at
160 ꢁC under argon atmosphere gave only 25–39%
yields. Cleavage reactions performed in common sol-
vents such as ethanol or dimethylformamide led to the
decomposition of nosyl epimines (loss of nosyl group
or rearrangement of the epimine to a hexenopyranose12).
However, we found that the reaction could be performed
at lower temperature 100–120 ꢁC if N-methylpyridinium
tosylate in 50% (w/w) was used as an ionic-liquid envi-
ronment. Under these reaction conditions, pseudodisac-
O
O
O
OH
OH
BnO
HO
OH
OBn
O
O
Ns
O
O
8 R = R1
i)
N
NHNs
9 R = R2
NH2
+
R
10 R = R3
5 R = R1
6 R = R2
7 R = R3
BnO
BnO
1
NHR
O
O
O
O
11 R = R1
12 R = R2
13 R = R3
i)
NHR
NH2
+
R
5 R = R1
6 R = R2
7 R = R3
BnO
BnO
N
Ns
NHNs
2
O
O
O
O
O
O
O
O
14 R = R1
15 R = R2
16 R = R3
O
O
O
O
i)
NHNs
i)
ii)
NNs
NH2
+
R
OH
OH
N3
NH2
5 R = R1
6 R = R2
7 R = R3
RNH
BnO
BnO
HO
HO
OBn
OBn
3
5
NH2
O
N3
OH
OH
6
O
O
O
O
O
O
O
17 R = R1
18 R = R2
19 R = R3
i)
i)
OH
NHR
OH
NH2
R
+
5 R = R1
6 R = R2
7 R = R3
NsN
H2N
NsNH
N3
OBn
OBn
4
OBn
7
OBn
Scheme 1. Preparation of sugar nucleophiles 5–7. Reagents and
conditions: (i) 1. NaBH4/THF, rt, 2. MeOH, reflux, 5—79%, 7—
68%; (ii) H2, 10% Pd/C, MeOH, rt, 91%.
Scheme 2. Reactions of 2,3-manno-, 2,3-allo-, 3,4-galacto, and 3,4-allo-
epimine 1–4 with 2-, 3-, and 4-amino derivatives 5, 6, and 7. Reagent
and condition: (i) N-methylpyridinium tosylate, 115–120 ꢁC.

J. Kroutil, M. Budeˇsˇı´nsky´ / Carbohydrate Research 342 (2007) 147–153
Table 1. 1H NMR chemical shifts of compounds 8–19 in CDCl3
149
Compound H-1
H-2
H-3
H-4
H-5
H-6endo
H-6exo
Other protons
8
5.42 t
5.02 m
2.53 m
2.21 br
3.74 m
3.55 m
3.50 m
3.25 dd
4.50 m
4.50 m
4.08 dd
3.86 dd
3.70 dd 2 · OBn: 4.71 d + 4.61 d, 4.60 d + 4.56 d,
3.62 dd 7.27–7.38 m (10H); NH–Ns: 6.17 d, 8.08 m,
7.83 m, 7.68 m (2H); OH: 2.35 d
9
5.45 t
5.22 t
2.57 q
3.20 m
3.77 br d 3.56 br s 4.55 dt
4.14 dd
3.97 dd
3.74 dd OBn: 4.66 s (2H), 7.32–7.41 (5H); NH–Ns:
3.56 dd 6.20 br d, 8.12 m, 7.85 m, 7.73 m (2H);
OH + NH: 2.70 br + 2.30 br
2.41 m
3.10 m
4.33 m
10
5.49 t
5.32 br s 3.08 dd
2.53 br s 3.82 m
3.53 q
2.11 dd
4.53 dt
4.15 br d 3.38 dd
4.10 dd
3.72 dd 2 · OBn: 4.68 d + 4.62 d, 4.55 s (2H),
3.46 dd 7.29–7.37 m (10H); NH–Ns: 6.11 br d, 8.06 dd,
7.82 dd, 7.69 dt, 7.61 dt; OH + NH: 2.33 br d,
2.19 br s
3.39 m
11a
5.28 t
5.24 t
3.58 m
2.52 m
2.91 p
3.68 m
3.17 m
3.36 m
4.50 m
4.59 m
4.16 dd
4.06 dd
3.57 dd 2 · OBn: 4.63 d + 4.55 d, 4.48 d + 4.42 d,
3.72 dd 7.25–7.36 m (10H); NH–Ns: 8.17 dd, 7.79 dt,
7.75 dd, 7.72 dt
12
13
5.34 br s 3.58 m
5.34 br s 3.16 q
2.85 p
2.68 p
3.24 q
3.46 q
4.57 m
4.49 m
4.07 dd
4.03 dd
3.69 dd OBn: 4.55 d + 4.46 d, 7.26–7.36 (5H); NH–Ns:
3.68 dd 6.53 br, 8.16 m, 7.75 m (2H), 7.69 m
5.11 t
5.45 t
3.61 m
3.32 t
2.88 p
3.79 m
3.25 m
2.40 m
4.55 m
4.30 br d 4.03 dd
4.34 dd
3.62 dd 2 · OBn: 4.79 d + 4.67 d, 4.60 d + 4.54 d,
3.64 dd 7.29–7.41 m (10H); NH–Ns: 6.36 br s, 7.86 dd,
7.75 dd, 7.65 dt, 7.60 dt; NH + OH: 2.34 br s
14
5.39 t
5.35 t
3.16 q
2.73 m
3.78 m
3.71 m
2.81 m
3.38 dd
4.54 m
4.54 m
4.12 dd
3.92 dd
3.73 dd 2 · OBn: 4.66 d + 4.57 d, 4.37 d + 4.15 d,
3.69 dd 7.22–7.36 m (8H), 7.05 m (2H); NH–Ns: 6.03 d,
8.16 m, 7.82 m (2H), 7.70 dt; OH: 2.64 d
15
16
5.39 t
5.34 t
3.17 q
3.35 q
3.69 m
3.01 p
2.84 q
3.56 m
4.49 dt
4.54 dt
4.16 br d 3.73 dd OBn: 4.26 d + 4.21 d, 7.26 m (3H), 7.04 m (2H);
4.32 dd
3.68 dd NH–Ns: 6.05 br, 8.26 dd, 7.84 dd, 7.79 dt, 7.73 dt
5.39 t
5.47 t
3.11 q
3.30 m
3.76 m
3.79 m
2.85 m
2.74 m
4.45 m
4.52 m
4.13 dd
4.06 dd
3.71 dd 2 · OBn: 4.61s (2H), 4.32 d + 4.14 d, 7.20–7.36 m
3.72 dd (8H), 7.01 m (2H); NH–Ns: 6.06 br d, 8.16 m,
7.83 m, 7.73 m (2H); OH: 2.53 br d
17
5.40 t
5.12 t
3.22 q
2.49 b
2.82 m
3.72 m
3.63 m
3.38 m
4.35 dt
4.55 dt
4.32 dd
4.03 dd
3.51 dd 2 · OBn: 4.66 s (2H), 4.48 d + 4.45 d, 7.24–7.38 m
3.68 dd (10H); NH–Ns: 6.52 d, 8.14 dd, 7.76 dd, 7.72 dt,
7.68 dt; OH: 2.56 d; NH: 2.03 br
18a
19
5.43 m
5.33 t
3.16 q
3.23 q
2.68 p
2.87 p
3.62 m
3.16 q
4.40 dt
4.41 dt
3.79 dd
4.22 dd
3.60 dd OBn: 4.54 d + 4.51 d, 7.26–7.36 (5H); NH–Ns:
3.64 dd 8.19 dd, 7.82 dd, 7.80 dt, 7.74 dt
5.33 m
5.46 t
3.04 m
3.28 q
2.87 m
3.50 dp
3.62 m
2.57 m
4.42 dt
4.40 dt
4.54 dd
4.11 dd
3.63 dd 2 · OBn: 4.53 d + 4.43 d, 4.26 d + 4.22 d,
3.69 dd 7.25–7.34 m (8H), 7.11 m (2H); NH–Ns:
6.48 br s, 8.16 dd, 7.74 dd, 7.71 dt, 7.67 dt;
NH: 2.14 br d; OH: 2.38 d
First line for each compound represents parameters of diamino substituted tetrahydropyran ring.
a The mixture of CDCl3 + CD3OD (9:1) was used due to very low solubility of the sample in CDCl3.
1
using correlated homonuclear 2D-COSY and hetero-
nuclear 1H, 13C-2D-HMQC spectra. The diamino substi-
tuted unit is difficult to recognize from 1H NMR spectra,
since only the ˜CH–NH– protons are significantly up-
field shifted (d 2.1–3.0 ppm) while ˜CH–Ns protons ap-
pear at d 3.5–3.8 ppm together with ˜CH–OR protons,
but it can be clearly recognized by two upfield signals
in 13C NMR spectra (˜CH–NH– at d 56.7–60.9 ppm
and ˜CH–Ns at d 50.8–55.2 ppm).
The gluco configuration of all 1,6-anhydrohexose
units in prepared pseudodisaccharides 8–19 is confirmed
by the observed values of proton–proton coupling
constants (vicinal J1,2, J2,3, J3,4, J4,5 ꢀ 1.3–2.8 Hz and
long-range J1,3, J2,4, J3,5 ꢀ 0.5–1.8 Hz are typical for
1,6-anhydrohexose derivatives with gluco configura-
tion14–16). The tetrahydropyran ring in some derivatives
adopts the preferred chair form C4 common for 1,6-
anhydrohexopyranoses15,17 as it is indicated by small
values of J2,3 and J3,4 constants (62.4 Hz). For the other
derivatives (cf. compounds 8–10, 14–15, 18), somewhat
higher values of J2,3, J3,4 couplings in the range 2.5–
5.1 Hz indicate the presence of certain population of less
preferred tetrahydropyran ring conformation (boat
form BO,3) in a conformational equilibrium. Com-
pounds 16 and 17 have boundary values (2.5–2.95 Hz)
for J2,3 and J3,4 couplings (Fig. 2).
When using the reference values J2,3 ꢀ J3,4 = 1.7 Hz
for 1C4-form and J2,3 ꢀ J3,4 = 8.8 Hz for BO,3-form (cal-
culated from a series of 1,6-anhydro-b-D-glucopyranose
derivatives by Grindley et al.17) we can estimate the
range of the BO,3-form population fractions for com-
pounds 8–10, 14–15, 18 as 11–48%.

150
J. Kroutil, M. Budeˇsˇı´nsky´ / Carbohydrate Research 342 (2007) 147–153
Table 2. 1H NMR coupling constants of compounds 8–19 in CDCl3
Compound
J(1,2)
J(2,3)
J(3,4)
J(4,5) J(5,6endo
)
J(5,6exo
)
J(6endo,6exo
)
J(gem) (OBn)
J(1,3)
J(2,4)
J(3,5) J(1,4)
8
1.8
a
1.8
3.1
2.0
3.4
1.8
1.7
0.6
0.8
5.2
5.2
8.0
7.5
12.3
12.2
1.3
1.2
1.3
0.9
1.7
a
0.6
<0.5
a
a
9
10
11b
12
13
14
15
16
17
18b
19
1.8
1.7
2.0
2.7
2.0
3.0
2.0
1.8
0.6
1.0
5.2
5.4
8.0
7.3
0.8
1.1
1.2
1.0
1.4
1.4
0.6
ꢁ0.5
0.6
<0.3
1.6
1.2
2.0
4.4
1.9
5.1
2.0
1.6
0.4
0.8
5.2
5.0
8.0
7.2
12.1
a
1.2
0.9
1.3
ꢁ0
1.4
0.8
a
a
a
a
a
ꢁ1.8
ꢁ1.6
1.4
1.4
ꢁ1.0
ꢁ1.2
1.6
2.1
ꢁ1.1
ꢁ1.2
1.8
2.1
0.8
0.8
5.5
5.5
7.5
7.4
11.6
12.0
ꢁ1.8
ꢁ1.6
1.4
1.2
ꢁ0.5
a
ꢁ1.2
1.5
1.8
1.8
1.8
0.7
0.8
5.6
5.6
7.5
7.5
12.1
a
1.2
1.0
0.6
<0.3
1.7
1.5
ꢁ1.5
2.1
2.1
1.4
1.8
0.7
0.8
5.4
5.3
7.3
7.3
12.1
12.2
1.7
1.5
1.4
1.1
1.5
1.5
0.7
ꢁ0.5
0.6
<0.3
2.5
1.5
1.1
2.7
4.2
2.3
4.2
1.9
1.5
0.5
0.8
5.1
5.2
8.0
7.4
12.3
12.0
1.35
1.0
1.0
0.6
1.0
1.0
2.0
1.3
2.7
3.2
3.1
3.2
1.3
1.7
0.5
0.8
4.9
5.2
7.9
7.3
12.1
a
1.2
1.2
1.0
0.9
1.3
1.3
0.7
0.4
1.6
1.7
2.95
1.8
2.5
2.0
1.6
2.1
<0.5
0.9
5.1
5.6
7.9
7.2
11.8
a
1.2
1.35
1.0
1.6
1.3
1.2
0.5
0.5
1.7
1.7
1.7
2.5
1.5
2.6
1.3
1.8
0.65
0.65
5.4
5.25
7.6
7.6
12.0
a
1.4
1.4
1.2
1.0
1.5
1.5
0.7
0.6
2.0
1.3
2.0
3.6
2.0
3.6
2.1
1.7
0.9
0.8
5.4
5.3
7.5
7.6
12.1
a
1.3
1.0
1.2
0.8
1.5
1.1
<0.3
<0.5
2.2
2.1
1.8
1.7
1.8
1.7
1.8
1.7
0.8
0.9
5.3
5.5
7.4
7.2
11.7
12.0
1.7
1.3
1.6
1.0
1.8
1.6
0.7
0.8
First line for each compound represents parameters of diamino substituted tetrahydropyran ring.
a Value of parameter could not be estimated.
b The mixture of CDCl3 + CD3OD (9:1) was used due to very low solubility of the sample in CDCl3.
3. Experimental
3.1. General remarks
ate was prepared by mixing of commercially available
methyl tosylate with 1.1 equiv of dry pyridine at room
temperature and drying of the resulting solid in a vac-
uum desiccator over P2O5. All reactions (except hydro-
genation) were carried out under argon atmosphere.
Solutions and extracts were dried over anhydrous
sodium sulfate. Residues from evaporated chromato-
graphic fractions were dried in a desiccator over P2O5
and then crystallized from the given solvent mixtures.
Melting points were determined on a Boe¨tius melting-
point microapparatus and are uncorrected. The optical
rotations were measured on an Autopol III (Rudolph
1
Research, Flanders, NJ) polarimeter at 25 ꢁC. The H
and 13C NMR spectra were measured on a Varian
UNITY-500 instrument (1H at 500 MHz and 13C at
125.7 MHz) in CDCl3 (ref.: TMS for 1H and the chloro-
form signal at d 77.0 ppm for 13C) at 25 ꢁC. The 1H, 1H-
COSY and 1H, 13C-HMQC techniques were used for the
structural assignments. TLC was carried out on
MERCK DC Alufolien with Kiesegel F254 with the fol-
lowing solvent systems: S1 hexane–ethyl acetate—3:2
and S2 ethyl acetate. TLC plates were visualized by UV
detection at 254 nm and by an anisaldehyde solution in
sulfuric acid. Column chromatography was performed
on silica gel 60 MERCK (70–230 mesh ASTM) with hex-
ane–ethyl acetate gradient elution. The solvents were
evaporated on a vacuum rotary evaporator at 40 ꢁC.
Light petroleum (PE) refers to the 40–60 ꢁC distillation
fraction. 2-Nitrobenzenesulfonyl chloride (purity 97%)
was purchased from Fluka. N-Methylpyridinium tosyl-
1
The H NMR spectral parameters are given in Tables 1
and 2, and those of 13C NMR spectra are given in Table
3.
3.2. 2-Amino-1,6-anhydro-4-O-benzyl-2-deoxy-b-D-gluco-
pyranose (5)
1,6-Anhydro-2-azido-4-O-benzyl-2-deoxy-b-D-gluco-
pyranose8 (5.17 g, 18.7 mmol), NaBH4 (1.4 g, 37 mmol),
and tetrahydrofuran (50 mL) were mixed and stirred at
rt for 44 h. Methanol (20 mL) was added and the mix-
ture was being refluxed for 2 h. After cooling to rt, the
solvents were evaporated off and a white solid was par-
titioned between dichloromethane (50 + 2 · 15 mL) and
10% aqueous NaOH (20 mL). The combined dichloro-
methane extracts were dried and evaporated. The resi-

J. Kroutil, M. Budeˇsˇı´nsky´ / Carbohydrate Research 342 (2007) 147–153
151
Table 3. 13C NMR chemical shifts of compounds 8–19 in CDCl3
Compound C-1 C-2 C-3 C-4 C-5 C-6 Other carbons
8
102.05 58.46 52.77 76.64 74.96 65.48 2 · OBn: 71.42, 71.10, 137.65, 137.51, 128.47(4), 127.92(2), 127.88(2), 127.77(2);
102.80 60.27 70.25 78.88 74.79 66.06 NH–Ns: 147.81, 133.71, 133.66, 132.88, 130.91, 125.54
9
101.86 58.37 51.96 76.78 74.58 65.53 OBn: 71.51, 137.14, 127.98(2), 128.64(2), 128.20; NH–Ns: 147.81, 133.88, 133.47,
102.31 71.04 60.65 71.80 76.70 65.66 133.10, 130.94, 125.58
10
11a
12
13
14
15
16
17
18a
19
102.54 58.51 51.31 76.87 74.40 65.47 2 · OBn: 71.86, 71.27, 137.63, 137.29, 128.56(2), 128.48(2), 128.06, 127.94,
101.21 80.44 71.46 60.40 76.90 67.50 127.91(4); NH–Ns: 147.85, 133.76, 133.68, 132.86, 131.08, 125.56
100.76 54.40 56.81 76.48 73.85 65.18 2 · OBn: 71.29, 70.94, 137.40, 137.10, 128.38(2), 128.36(2), 127.83(2), 127.65(2),
101.90 59.02 68.60 78.46 73.99 65.43 127.58(2), NH–Ns: 147.37, 134.74, 133.49, 132.99, 130.11, 125.29
101.05 54.99 57.81 76.20 73.93 65.55 OBn: 71.16, 137.18, 128.58(2), 128.08, 128.02(2); NH–Ns: 147.49, 135.01, 133.62,
102.08 70.38 61.50 70.47 76.81 65.58 133.21, 130.16, 125.41
100.67 54.91 57.65 77.31 74.11 65.53 2 · OBn: 71.92, 71.10, 137.69, 137.36, 128.57(2), 128.49(2), 127.98, 127.92(2),
100.37 77.54 68.34 60.01 76.50 66.44 127.81, 127.58(2); NH–Ns: 147.52, 135.38, 133.29, 132.91, 129.93, 125.37
100.11 76.10 51.89 58.00 76.60a 66.33 2 · OBn: 71.64, 71.55, 137.86, 136.72, 128.48(2), 128.45(2), 128.05, 127.83,
103.41 60.43 71.11 80.21 74.97a 66.61 127.78(2), 127.60(2); NH–Ns: 147.82, 133.93, 133.67, 133.03, 131.11, 125.35
99.84 76.15 50.84 58.20 77.16 66.49 OBn: 71.76, 136.52, 128.50(2), 128.16, 127.53(2); NH–Ns: 147.78, 137.70, 133.95,
101.88 70.93 60.50 70.68 76.76 65.42 133.25, 131.29, 125.37
100.27 75.92 52.28 57.65 76.46 66.40 2 · OBn: 72.00, 71.55, 137.68, 136.85, 128.47(2), 128.40(2), 127.99, 127.91,
101.05 78.62 69.58 59.40 76.08 67.00 127.86(2), 127.49(2); NH–Ns: 147.84, 133.79, 133.73, 132.96, 130.95, 125.43
100.17 76.22 57.19 54.93 75.76 65.59 2 · OBn: 71.90, 71.62, 137.46, 137.13, 128.56(2), 128.54(2), 128.07, 128.01,
101.68 59.81 70.26 78.31 74.69 65.82 127.95(2), 127.86(2); NH–Ns: 135.52, 147.56, 125.44, 133.00, 133.39, 130.02
100.25 75.94 60.85 54.09 76.78 65.28 OBn: 71.73, 136.94, 128.46(2), 128.05, 128.00(2); NH–Ns: 134.82, 147.48, 125.32,
102.09 70.38 56.97 69.58 75.75 65.84 133.14, 133.57, 130.12
99.93 76.59 56.73 55.18 75.73 65.76 2 · OBn: 71.79, 71.72, 137.35, 137.28, 128.52(2), 128.42(2), 128.04, 127.90,
99.87 77.12 67.86 58.70 77.01 66.43 127.64(2), 127.59(2); NH–Ns: 135.61, 147.51, 125.41, 133.06, 133.25, 129.99
First line for each compound represents parameters of diamino substituted tetrahydropyran ring.
a The mixture of CDCl3 + CD3OD (9:1) was used due to very low solubility of the sample in CDCl3.
stants and 1H and 13C NMR data matched that
D-gluco configuration
reported.10
O
H
R2
H
O
O
R3
R2
3.4. 4-Amino-1,6-anhydro-2-O-benzyl-4-deoxy-b-
D-glucopyranose (7)
O
R1
R1
R3
H
1C4
BO,3
1,6-Anhydro-4-azido-2-O-benzyl-4-deoxy-b-D-gluco-
pyranose20 (3.5 g, 12.6 mmol), NaBH4 (1.0 g, 26 mmol),
and tetrahydrofuran (40 mL) were mixed and stirred at
rt for 21 h. Methanol (10 mL) was added and the mix-
ture was being refluxed for 2 h. After cooling to rt, the
solvents were evaporated off and a white solid was par-
titioned between dichloromethane (50 + 2 · 15 mL) and
10% aqueous NaOH (20 mL). The combined dichloro-
methane extracts were dried and evaporated. The resi-
due was crystallized from EtOH–Et2O–PE mixture to
Figure 2. Conformational equilibrium of tetrahydropyran ring.
due was crystallized from EtOH–Et2O–PE mixture to
afford 3.7 g of 5. Yield 79%, mp 148–152 ꢁC (lit.18 mp
151–152 ꢁC). H and 13C NMR data were the same as
1
described in Ref. 18.
3.3. 3-Amino-1,6-anhydro-3-deoxy-b-D-glucopyranose (6)
1
afford 2.2 g (68%). Physical constants and H and 13C
A mixture of 1,6-anhydro-3-azido-3-deoxy-b-D-gluco-
pyranose19 (1.8 g, 9.6 mmol), methanol (50 mL), and
10% palladium on charcoal (50 mg) was hydrogenated
under atmospheric pressure at rt for 2 h. The catalyst
was filtered off with suction and washed with 5% (w/v)
NH3 solution in methanol (50 mL). The combined fil-
trates were evaporated and dried in a vacuum desiccator
over P2O5 for 2 h. The residue was crystallized from
EtOH–Et2O mixture to afford 1.4 g (91%). Physical con-
NMR data matched that reported.11
3.5. General procedure for aziridine-ring cleavage
A mixture of nosylepimine, aminoglucose, and equal
weight amount (50% w/w) of N-methylpyridinium
tosylate was placed into a silicone oil bath preheated
to 130 ꢁC. After melting (ca. 10 min), the temperature

152
J. Kroutil, M. Budeˇsˇı´nsky´ / Carbohydrate Research 342 (2007) 147–153
of the bath was lowered and maintained between 115
and 120 ꢁC and the mixture was stirred for the given
time. The reaction course was monitored by TLC in S1
(for compounds: 8, 10, 11, 13, 14, 16, 17, and 19) or
S2 (for compounds: 9, 12, 15, and 18) solvent system.
The mixture was cooled to rt and partitioned between
water (5 mL) and EtOAc (5 mL). An additional amount
of water (10 mL) was added and the mixture was ex-
tracted by dichloromethane (3 · 20 mL). The combined
dichloromethane extracts were dried and evaporated.
The residue was chromatographed on silica gel (20–
30 g, gradient elution from hexane–ethyl acetate 3:2
mixture to pure ethyl acetate) to remove traces of
unreacted nosylepimine and to obtain pure pseudo-
disaccharide derivative. Yields and characterization
data are given below for individual compounds.
499 mg (75%); mp 191–192 ꢁC (EtOH–Et2O–PE); [a]D
À38 (c 0.33 CHCl3). Anal. Calcd for C32H35N3O11S:
C, 57.39; H, 5.27; N, 6.27; S, 4.79. Found C, 57.29; H,
5.15; N, 6.06; S, 5.06.
3.5.5. 1,6-Anhydro-3-(1,6-anhydro-3-deoxy-b-D-glucopyr-
anos-3-ylamino)-4-O-benzyl-2,3-dideoxy-2-(2-nitrobenz-
ene-1-sulfonamido)-b-D-glucopyranose (12). Prepared
from nosylepimine 2 (418 mg, 1 mmol), 3-aminoglucose
6 (200 mg, 1.2 mmol), and N-methylpyridinium tosylate
(600 mg). Reaction time 105 min. Yield 381 mg (66%);
mp 75–79 ꢁC (EtOAc–Et2O–PE); [a]D À56 (c 0.25
CHCl3). Anal. Calcd for C25H29N3O11S: C, 51.81; H,
5.04; N, 7.25; S, 5.53. Found C, 51.45; H, 5.03; N,
6.93; S, 5.36.
3.5.6. 1,6-Anhydro-3-(1,6-anhydro-2-O-benzyl-4-deoxy-
b-D-glucopyranos-4-ylamino)-4-O-benzyl-2,3-dideoxy-2-
(2-nitrobenzene-1-sulfonamido)-b-D-glucopyranose (13).
Prepared from nosylepimine 2 (418 mg, 1 mmol), 4-
aminoglucose 7 (377 mg, 1.5 mmol), and N-methyl-
pyridinium tosylate (800 mg). Reaction time 2 h. Yield
538 mg (80%); mp 65–68 ꢁC (EtOH–Et2O–PE); [a]D 16
(c 0.23 CHCl3). Anal. Calcd for C32H35N3O11S: C,
57.39; H, 5.27; N, 6.27; S, 4.79. Found C, 57.29; H,
5.33; N, 5.88; S, 4.78.
3.5.1. 1,6-Anhydro-2-(1,6-anhydro-4-O-benzyl-2-deoxy-
b-D-glucopyranos-2-ylamino)-4-O-benzyl-2,3-dideoxy-
3-(2-nitrobenzene-1-sulfonamido)-b-D-glucopyranose (8).
Prepared from nosylepimine 1 (418 mg, 1 mmol), 2-
aminoglucose 5 (377 mg, 1.5 mmol), and N-methyl-
pyridinium tosylate (800 mg). Reaction time 2 h. Yield
621 mg (93%); mp 70–75 ꢁC (EtOH–Et2O–PE); [a]D
À55 (c 0.28 CHCl3). Anal. Calcd for C32H35N3O11S:
C, 57.39; H, 5.27; N, 6.27; S, 4.79. Found: C, 56.99;
H, 5.26; N, 5.98; S, 5.13.
3.5.7. 1,6-Anhydro-4-(1,6-anhydro-4-O-benzyl-2-deoxy-
b-D-glucopyranos-2-ylamino)-2-O-benzyl-3,4-dideoxy-3-
(2-nitrobenzene-1-sulfonamido)-b-D-glucopyranose (14).
Prepared from nosylepimine 3 (418 mg, 1 mmol), 2-
aminoglucose 5 (377 mg, 1.5 mmol), and N-methyl-
pyridinium tosylate (800 mg). Reaction time 2 h. Yield
428 mg (64%); mp 169–170 ꢁC (EtOAc–Et2O–PE); [a]D
À87 (c 0.26 CHCl3). Anal. Calcd for C32H35N3O11S:
C, 57.39; H, 5.27; N, 6.27; S, 4.79. Found C, 57.04; H,
5.33; N, 5.95; S, 4.74.
3.5.2. 1,6-Anhydro-2-(1,6-anhydro-3-deoxy-b-D-glucopyr-
anos-3-ylamino)-4-O-benzyl-2,3-dideoxy-3-(2-nitrobenz-
ene-1-sulfonamido)-b-D-glucopyranose
(9). Prepared
from nosylepimine 1 (418 mg, 1 mmol), 3-aminoglucose
6 (200 mg, 1.2 mmol), and N-methylpyridinium tosylate
(600 mg). Reaction time 90 min. Yield 440 mg (76%);
mp 156–157 ꢁC (EtOAc–Et2O–PE); [a]D À89 (c 0.29
CHCl3). Anal. Calcd for C25H29N3O11S: C, 51.81; H,
5.04; N, 7.25; S, 5.53. Found: C, 51.72; H, 4.98; N,
6.99; S, 5.54.
3.5.8. 1,6-Anhydro-4-(1,6-anhydro-3-deoxy-b-D-glucopyr-
anos-3-ylamino)-2-O-benzyl-3,4-dideoxy-3-(2-nitrobenz-
ene-1-sulfonamido)-b-D-glucopyranose (15). Prepared
3.5.3. 1,6-Anhydro-2-(1,6-anhydro-2-O-benzyl-4-deoxy-
b-D-glucopyranos-4-ylamino)-4-O-benzyl-2,3-dideoxy-3-
(2-nitrobenzene-1-sulfonamido)-b-D-glucopyranose (10).
Prepared from nosylepimine 1 (418 mg, 1 mmol), 4-
aminoglucose 7 (377 mg, 1.5 mmol), and N-methyl-
pyridinium tosylate (800 mg). Reaction time 2 h. Yield
574 mg (86%); mp 72–75 ꢁC (EtOH–Et2O–PE); [a]D
À65 (c 0.3 CHCl3). Anal. Calcd for C32H35N3O11S: C,
57.39; H, 5.27; N, 6.27; S, 4.79. Found: C, 57.37; H,
5.20; N, 6.04; S, 4.93.
from nosylepimine
3 (418 mg, 1 mmol), 3-amino-
glucose 6 (200 mg, 1.2 mmol), and N-methylpyridinium
tosylate (600 mg). Reaction time 2 h. Yield 476 mg
(82%, after crystallization 315 mg, 54%); mp 80–
85 ꢁC (EtOAc–Et2O–PE); [a]D À93 (c 0.26 CHCl3).
Anal. Calcd for C25H29N3O11S: C, 51.81; H, 5.04; N,
7.25; S, 5.53. Found C, 51.73; H, 5.13; N, 6.95; S, 5.76.
3.5.9. 1,6-Anhydro-4-(1,6-anhydro-2-O-benzyl-4-deoxy-
b-D-glucopyranos-4-ylamino)-2-O-benzyl-3,4-dideoxy-3-
(2-nitrobenzene-1-sulfonamido)-b-D-glucopyranose (16).
Prepared from nosylepimine 3 (418 mg, 1 mmol), 4-
aminoglucose 7 (377 mg, 1.5 mmol), and N-methyl-
pyridinium tosylate (800 mg). Reaction time 2 h. Yield
450 mg (67%); mp 72–76 ꢁC (EtOH–Et2O–PE); [a]D
3.5.4. 1,6-Anhydro-3-(1,6-anhydro-4-O-benzyl-2-deoxy-
b-D-glucopyranos-2-ylamino)-4-O-benzyl-2,3-dideoxy-2-
(2-nitrobenzene-1-sulfonamido)-b-D-glucopyranose (11).
Prepared from nosylepimine 2 (418 mg, 1 mmol), 2-
aminoglucose 5 (377 mg, 1.5 mmol), and N-methyl-
pyridinium tosylate (800 mg). Reaction time 2 h. Yield

J. Kroutil, M. Budeˇsˇı´nsky´ / Carbohydrate Research 342 (2007) 147–153
153
À106 (c 0.29 CHCl3). Anal. Calcd for C32H35N3O11S: C,
References
57.39; H, 5.27; N, 6.27; S, 4.79. Found C, 57.27; H, 5.13;
N, 6.03; S, 4.83.
1. Ogawa, S.; Yokoi, S.; Kimura, N.; Shibata, Y.; Chida, N.
Carbohydr. Res. 1988, 181, 57–66.
2. Carvalho, I.; Haines, A. H. J. Chem. Soc., Perkin Trans. 1
1999, 1795–1800.
3.5.10. 1,6-Anhydro-3-(1,6-anhydro-4-O-benzyl-2-deoxy-
b-D-glucopyranos-2-ylamino)-2-O-benzyl-3,4-dideoxy-4-
(2-nitrobenzene-1-sulfonamido)-b-D-glucopyranose (17).
Prepared from nosylepimine 4 (418 mg, 1 mmol), 2-
aminoglucose 5 (377 mg, 1.5 mmol), and N-methyl-
pyridinium tosylate (800 mg). Reaction time 1 h
45 min. Yield 549 mg (82%); mp 69–72 ꢁC (EtOH–
Et2O–PE); [a]D À19 (c 0.29 CHCl3). Anal. Calcd for
C32H35N3O11S: C, 57.39; H, 5.27; N, 6.27; S, 4.79.
Found C, 57.03; H, 5.26; N, 6.00; S, 4.91.
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3. Bleriot, Y.; Dintinger, T.; Guillo, N.; Tellier, C. Tetra-
hedron Lett. 1995, 36, 5175–5178.
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´
´
´
8. Karban, J.; Budeˇsˇınsky, M.; Cerny, M.; Trnka, T. Collect.
Czech. Chem. Commun. 2001, 66, 799–819.
9. Nagy, L.; Yamaguchi, T.; Mitsunaga, T.; Wakita, H.;
Jezowska-Bojczuk, M.; Nomura, M.; Kozlowski, H. Ach-
Models Chem. 1998, 135, 941–951.
3.5.11. 1,6-Anhydro-3-(1,6-anhydro-3-deoxy-b-D-gluco-
pyranos-3-ylamino)-2-O-benzyl-3,4-dideoxy-4-(2-nitrobenz-
ene-1-sulfonamido)-b-D-glucopyranose (18). Prepared
from nosylepimine 4 (418 mg, 1 mmol), 3-aminoglucose
6 (180 mg, 1.12 mmol), and N-methylpyridinium tosylate
(600 mg). Reaction time 90 min. Yield 391 mg (68%); mp
156–159 ꢁC (EtOAc–Et2O–PE); [a]D À36 (c 0.35 CHCl3).
Anal. Calcd for C25H29N3O11S: C, 51.81; H, 5.04; N,
7.25; S, 5.53. Found C, 51.81; H, 5.00; N, 7.10; S, 5.58.
ˇ
´
´
´
10. Trnka, T.; Cerny´, M.; Budeˇsˇınsky, M.; Pacak, J. Collect.
Czech. Chem. Commun. 1975, 40, 3038–3045.
ˇ
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11. Cerny´, M.; Cerny´, I.; Pacak, J. Collect. Czech. Chem.
Commun. 1976, 41, 2942–2951.
ˇ
´
´
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12. Kroutil, J.; Karban, J.; Trnka, T.; Budeˇsˇınsky, M.; Cerny,
M. Collect. Czech. Chem. Commun. 2002, 67, 1805–
1819.
13. Furst, A.; Plattner, P. A. Abstracts of Papers, 12th
¨
International Congress on Pure Applied Chemistry, New
York, 1951; p 409.
3.5.12. 1,6-Anhydro-3-(1,6-anhydro-2-O-benzyl-4-deoxy-
b-D-glucopyranos-4-ylamino)-2-O-benzyl-3,4-dideoxy-4-
(2-nitrobenzene-1-sulfonamido)-b-D-glucopyranose (19).
Prepared from nosylepimine 4 (418 mg, 1 mmol), 4-
aminoglucose 7 (377 mg, 1.5 mmol), and N-methyl-
pyridinium tosylate (800 mg). Reaction time 2 h. Yield
ˇ
´
´
´
14. Budeˇsˇınsky, M.; Trnka, T.; Cerny, M. Collect. Czech.
Chem. Commun. 1979, 44, 1949–1964.
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15. Cerny´, M.; Staneˇk, J. Adv. Carbohydr. Chem. Biochem.
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17. Grindley, T. B.; Cude, A.; Kralovic, J.; Thangarasa, R. In
Frontiers in Biomedicine and Biotechnology. Levoglucose-
none and Levoglucosans, Chemistry and Applications; ATL
Press: New York, 1994; pp 147–164.
598 mg (89%); mp 70–72 ꢁC (EtOH–Et2O–PE); [a]D
3
(c 0.44 CHCl3). Anal. Calcd for C32H35N3O11S: C,
57.39; H, 5.27; N, 6.27; S, 4.79. Found C, 57.11; H,
5.36; N, 6.02; S, 4.74.
ˇ
´
´
´
ˇˇ´
´
18. Cerny´, M.; Julakova, O.; Pacak, J.; Budesınsky, M.
Collect. Czech. Chem. Commun. 1975, 40, 2116–
2119.
19. Paulsen, H.; Koebernick, H.; Stenzel, W.; Ko¨ll, P.
Tetrahedron Lett. 1975, 16, 1493–1494.
Acknowledgments
20. van der Klein, P. A. M.; Filemon, W.; Veeneman, G. H.;
van der Marel, G. A.; van Boom, J. H. J. Carbohydr.
Chem. 1992, 11, 837–848.
ˇ
´
The authors thank Mgr. B. Sperlichova for optical
rotation measurements, Grant Agency of the Czech
Republic (Grant 203/02/D047) and Grant Agency of
Charles University in Prague (Project 311/2006/B-CH/
PrF) for financial support.
ˇ
´
´
´
21. Kroutil, J.; Trnka, T.; Budeˇsˇınsky, M.; Cerny, M. Eur. J.
Org. Chem. 2002, 2002, 2449–2459.
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22. Kroutil, J.; Jenisˇtova, J. Collect. Czech. Chem. Commun.
2005, 70, 2075–2085.