Stereoselective synthesis of novel N-b-glycosyl sulfonamides by sulfonamidoglycosylation of per-O-acetylated sugars

Article abstract of DOI:10.1055/s-0029-1217045

A series of novel N-glycosyl sulfonamides is prepared by sulfonamidoglycosylation of per-O-acetylated sugars. The products which contain an unnatural sulfonamide moiety at the anomeric centre are obtained in very good yields and with excellent β-stereoselectivity, even with per-O-acetylated D-mannose. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1217045

PAPER
4143
Stereoselective Synthesis of Novel N-b-Glycosyl Sulfonamides
by Sulfonamidoglycosylation of Per-O-acetylated Sugars
S
tereoselectiv
e
S
ynthesis
d
of Novel
N
-
r
b
-Glycos
o
yl Sulfonamide
s
Alfonso Colinas,* Carlos Agustín Témpera, Oscar Mariano Rodríguez, Rodolfo Daniel Bravo
LADECOR, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata,
47 y 115 (1900) La Plata, Argentina
Fax +54(221)4226947; E-mail: pcolinas@quimica.unlp.edu.ar
Received 17 July 2009; revised 11 August 2009
Dedicated to Prof. Dr. Albrecht Lieberknecht on the occasion of his 60th birthday
fonamides from readily available sugar per-O-acetates is
desirable. In this context, we report herein the results of
our studies on the synthesis of N-glycosyl sulfonamides
from per-O-acetylated carbohydrates (Scheme 1).
Abstract: A series of novel N-glycosyl sulfonamides is prepared by
sulfonamidoglycosylation of per-O-acetylated sugars. The products
which contain an unnatural sulfonamide moiety at the anomeric
centre are obtained in very good yields and with excellent b-stereo-
selectivity, even with per-O-acetylated D-mannose.
BnO OBn
BnO OBn
Key words: sulfonamidoglycosylation, per-O-acetylated carbohy-
drates, sulfonamides, b-stereoselectivity, exo-anomeric effect
O
O
H
H
N
O
N
O
BnO
BnO
S
S
O
O
In many cases, the use of carbohydrates as drugs has a sig-
nificant drawback: they are sensitive to enzymes and acid-
ic or basic media. Thus, the design of mimetics that bind
to enzymes, but which are not processed to products in the
usual way, is an active area of research.1 An unusual en-
zyme-resistant replacement for the glycosidic linkage is
the sulfonamide group which can be installed by coupling
of a glycosylamine and a sulfonic acid derivative. Howev-
er, glycosylamines are not stable and are very sensitive to
hydrolysis and anomerization.2 To overcome this problem
we have developed several methods for the sulfonami-
doglycosylation of sugar derivatives.3 We have previous-
ly reported that N-glycosyl sulfonamides can be prepared
by addition of sulfonamides to benzyl-protected glycals
on treatment with triphenylphosphine hydrobromide
(HBr·PPh3),4 to methyl glycosides on treatment with bo-
ron trifluoride–diethyl ether complex (BF3·Et2O)5 or per-
chloric acid–silica gel (HClO4·SiO2),6 to acetyl-protected
glycals via Ferrier rearrangement on treatment with boron
trifluoride–diethyl ether complex7 or fluoroboronic acid–
silica gel (HBF4·SiO2).8 These novel compounds are in-
hibitors of carbonic anhydrase,9 and potent growth inhib-
itors of hepatocellular (Hep-G2)4 and lung carcinoma
(A549) cell lines.10 Representative examples of N-glyco-
syl sulfonamide mimetics, in particular, those for which
assay results are available, are shown in Figure 1.4,9,11
A
B
potent growth inhibitors of Hep-G24
OAc
O
O
AcO
AcO
O
O
HN
HN
S
O
AcO
S O
NH2
NH2
potent inhibitor of hCA II9
C
D
selective inhibitor of hCA IX9
O
AcO
AcO
AcO
HN
O
S
O
NH2
E
potent growth inhibitor of A5499 and Hep-G211
Figure 1 Examples of N-glycosyl sulfonamides possessing biologi-
cal activity
O
O
S
H
O
O
R
NH2
O
N
OAc
(AcO)n
(AcO)n
S
R
O
promoter
Scheme 1 Sulfonamidoglycosylation of per-O-acetylated sugars
Per-O-acetylation is a commonly used technique for the
protection of hydroxy groups in carbohydrates. Per-O-
acetylated sugars are inexpensive and serve as useful in-
termediates for the synthesis of naturally occurring glyco-
sides, oligosaccharides and other glycoconjugates.12 Thus
a convenient method for the preparation of glycosyl sul-
As reported in Table 1, treatment of b-D-glucopyranose
pentaacetate 1 with two equivalents of ethanesulfonamide
in the presence of two equivalents of boron trifluoride–
diethyl ether complex as promoter, at room temperature,
provided the corresponding N-glycosyl ethanesulfon-
amide 5 (see Table 2, entry 1 for structures) in good yield
and with complete b-stereoselectivity. Reducing the
quantity of the promoter resulted in slower reactions
which were not complete even after 48 hours (Table 1, en-
tries 4 and 5). When smaller quantities of the sulfonamide
were used, lower yields of the products were obtained. In
SYNTHESIS 2009, No. 24, pp 4143–4148
x
x.
x
x
.
2
0
0
9
Advanced online publication: 19.10.2009
DOI: 10.1055/s-0029-1217045; Art ID: M04309SS
© Georg Thieme Verlag Stuttgart · New York

4144
P. A. Colinas et al.
PAPER
all cases, only the b-isomer was isolated. The anomeric
configuration of the starting per-O-acetylated D-glucopy-
ranoside had no influence on the stereochemical outcome
or on the yield of product (Table 1, entry 3). We have pre-
viously shown that heterogeneous catalysts are useful pro-
moters in the sulfonamidoglycosylations of methyl
glycosides and acetyl glycals.6,8 However, both fluorobo-
ronic acid–silica gel and perchloric acid–silica gel were
found to be ineffective for the synthesis of the N-glycosyl
sulfonamides.
Table 1 Reaction of b-D-Glucopyranose Pentaacetate 1 with
Ethanesulfonamide Under Various Conditionsa
Entry Promoter
Sulfonamide Temp Time Yield
(equiv)
(°C)
r.t.
40
(h)
12
12
12
12
12
24
24
24
24
(%)
82
50
84
65
40
0
1
2
3b
4
5
6
7
8
9
BF3·OEt2 (2 equiv)
2
BF3·OEt2 (2 equiv)
BF3·OEt2 (2 equiv)
BF3·OEt2 (1.5 equiv)
BF3·OEt2 (1 equiv)
HClO4·SiO2 (2 g)c
HClO4·SiO2 (4 g)c
HBF4·SiO2 (2 g)d
HBF4·SiO2 (4 g)d
2
2
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
1.5
1
The novel compound 2,3,4,6-tetra-O-acetyl-b-D-glucopy-
ranosyl ethanesulfonamide 5 was fully characterized us-
ing two-dimensional NMR spectroscopy. The presence of
the anomeric sulfonamido substituent resulted in a signif-
icant upfield shift of the resonance of the anomeric carbon
2
2
0
1
(d = 82.70 ppm). In the H NMR spectrum the anomeric
2
0
proton signal appeared at d = 4.76 ppm as a broad triplet
with a coupling constant of 8.4 Hz indicating the presence
of a 1,2-trans glycosidic linkage. The 1H NMR spectrum
of sulfonamide 5 also exhibited three triplets at d = 5.91,
5.02 and 4.93 ppm which were assigned to protons H-4,
H-3 and H-2, respectively. The J values of 9.6 Hz for
these signals reveal the axial orientation of these three
protons, and were useful in establishing the 4C1 conforma-
tion of the pyranose ring.
2
0
a All reactions were performed in MeCN.
b Reaction was performed using a mixture of a- and b-D-glucopyra-
nose pentaacetate (75:25).13,
c HClO4·SiO2 (0.5 mmol g–1).
d HBF4·SiO2 (0.5 mmol g–1).
Table 2 Reactions of Per-O-acetylated Sugars with Various Sulfonamidesa
Entry
Sugar (a:b)
Sulfonamide
Product
Time (h)
12
Yield (%)
82
OAc
OAc
O
O
AcO
AcO
H
N
O
1
EtSO2NH2
AcO
AcO
OAc
OAc
S
O
O
OAc
Et
1 (75:25)
5
OAc
OAc
O
AcO
AcO
H
N
O
2
1 (75:25)
4-MeC6H4SO2NH2
12
24
12
85
83
80
OAc
S
4–Tol
6
O
AcO
AcO
H
N
3b
1 (75:25)
H2NSO2NH2
O
OAc
S
O
NH2
7
OAc
AcO
OAc
AcO
AcO
O
O
H
O
O
4
EtSO2NH2
AcO
N
OAc
OAc
S
OAc
Et
2 (75:25)
8
OAc
AcO
O
H
N
O
5
2 (75:25)
4-MeC6H4SO2NH2
12
85
AcO
OAc
S
O
4–Tol
9
Synthesis 2009, No. 24, 4143–4148 © Thieme Stuttgart · New York

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Stereoselective Synthesis of Novel N-b-Glycosyl Sulfonamides
4145
Table 2 Reactions of Per-O-acetylated Sugars with Various Sulfonamidesa (continued)
Entry
6b
Sugar (a:b)
2 (75:25)
Sulfonamide
H2NSO2NH2
Product
Time (h)
24
Yield (%)
OAc
AcO
AcO
O
H
N
O
82
80
OAc
S O
NH2
10
OAc
OAc
OAc
O
OAc
OAc
O
AcO
H
O
7
MeSO2NH2
18
AcO
N
AcO
AcO
S
O
OAc
Me
3 (65:35)
3 (65:35)
11
OAc
O
AcO
H
N
8b
H2NSO2NH2
MeSO2NH2
H2NSO2NH2
48
78
82
72
O
S
AcO
O
NH2
12
AcO
AcO
O
O
H
N
O
O
9
1
AcO
AcO
OAc
OAc
S
OAc
Me
4 (25:75)
13
AcO
O
H
N
10b
4 (25:75)
10
O
AcO
OAc
S O
NH2
14
a All the reactions were performed using sulfonamide (2 equiv), BF3·OEt2 (2 equiv) in MeCN at r.t.
b Reaction performed using 4 equiv of sulfamide.
Next, this study was extended to other sulfonamides and mer. Another method to assign the anomeric
1
per-O-acetylated sugars. The reactions were performed configuration relies on the magnitude of the JC–H cou-
using boron trifluoride–diethyl ether complex as the pro- pling between the anomeric carbon and its attached pro-
moter, two equivalents of sulfonamide and acetonitrile as ton.14 In our case, measurement of this coupling constant
solvent. The results are reported in Table 2.
using coupled HSQC gave 1JC1–H1 values of 156.3 Hz for
compound 11 and 156.2 Hz for sulfamide 12. A related
compound, N-b-D-mannopyranosyl-thiophene-2-carbox-
amide was found to possess a coupling constant of similar
magnitude (1JC1–H1 = 156.5 Hz).15 Unfortunately, a-ano-
mers of the mannopyranosyl sulfonamides could not be
isolated, and hence in our case, the 1JC1-H1 coupling for the
b-anomer alone cannot be used as definitive proof of the
anomeric configuration.
The corresponding N-b-glycosyl sulfonamides were ob-
tained in very good yields and the 1H NMR spectra of the
product mixtures indicated the formation of single ano-
mers, exclusively. Surprisingly, in our hands, the reaction
of per-O-acetylated mannose with methanesulfonamide
or sulfamide afforded the corresponding b-sulfonami-
doglycosides. The stereochemistry of 2,3,4,6-tetra-O-
acetyl-b-D-mannopyranosyl methanesulfonamide 11 was
established unambiguously by observation of nuclear The reaction mixtures were easily purified by flash col-
Overhauser interactions between the anomeric hydrogen umn chromatography and/or crystallization to afford the
(d = 5.03 ppm) with protons H-5 (d = 3.73 ppm), H-2 (d = pure anomer. The H NMR, 13C NMR and 2D COSY
1
5.45 ppm) and the sulfonamide N–H (d = 5.83 ppm). The spectra and combustion analyses of the sulfonamides
presence of a correlation between H-1 and H-5 in the were in full agreement with their structures.
NOESY spectrum of 11 indicated that the anomeric hy-
The sulfonamidoglycosylation reactions using two equiv-
alents of sulfamide afforded a complex reaction mixture
containing N,N¢-substituted sulfamides and other prod-
ucts. When four equivalents of the nucleophile were used
drogen was situated on the a-face of the pyranose ring,
and therefore compound 11 was the b-anomer. The 2D
NOESY spectrum of sulfamide 12 contained similar cor-
relations, thereby confirming its structure as the b-ano-
Synthesis 2009, No. 24, 4143–4148 © Thieme Stuttgart · New York

4146
P. A. Colinas et al.
PAPER
the corresponding N-monosubstituted products were ob- tween the N–H proton and the anomeric hydrogen would
tained in very good yields.
enable the exo-anomeric interaction in the a-anomer.19 In
this conformation the hydrogen atom on the nitrogen
would be situated below the pyranose ring resulting in in-
creased steric interactions thereby favoring the equatorial
isomer (Figure 2).
The anomeric selectivity may be a direct consequence of
neighboring group participation by the acetyl moiety at C-
2, followed by attack of the sulfonamide to afford the b-
sulfonamidoglycoside. This analysis is true for all cases
except for D-mannose, which should afford N-a-sulfon-
amido glycosides (Scheme 2, path a). In the mannose se-
ries, direct coupling of a glycosyl donor with a glycosyl
acceptor to give an equatorial glycoside is complicated by
the presence of the axial C–O bond adjacent to the reac-
tion site which hinders equatorial approach of the acceptor
and, in the case of ester protecting groups, actively pro-
motes axial glycoside formation through anchimeric as-
sistance. The unusual stereochemical outcome can be
explained in terms of a thermodynamically controlled re-
action.4 Recently Petillo et al. reported that 2-b-iodo-1-a-
sulfonamidohexoses readily epimerize to b-isomers at C-
1 in acidic medium.16 The rearrangement was promoted
by electron-withdrawing protecting groups present in the
carbohydrate moiety. A similar epimerization of the kinet-
ically formed a-sulfonamidomannopyranosides could be
proposed for our reaction (Scheme 2, path d).17 We stud-
ied the reaction of per-O-acetylated D-mannopyranose 3
with methanesulfonamide over shorter reaction times
(one, two or four hours) in an attempt to isolate the a-ano-
mer. Unfortunately, there was no evidence of the a-man-
nopyranoside in the crude reaction mixtures.18
OAc
OAc
O
AcO
H
AcO
H
O
H
N
H
S
O
steric
interactions
R
Figure 2 Steric interactions present in the a-anomers of 11 and 12
The formation of acetylated 2-hydroxyglycopyranosides
during glycosidations of per-O-acetylated sugars has been
reported previously.20 However, these by-products were
not present in the reaction mixtures of the sulfonamido-
glycosylations performed via the method reported herein.
In conclusion, we have described a new and efficient syn-
thesis of N-b-glycosyl sulfonamides by sulfonamidogly-
cosylation of readily available per-O-acetylated sugars
utilizing boron trifluoride–diethyl ether complex as a pro-
moter and acetonitrile as the solvent. This coupling meth-
od allows for the preparation of various novel glycosides
which possess atypical functionality at the pyranose ano-
meric center, which may enable them to interact with the
active sites of carbohydrate-processing enzymes. The
presence of the unnatural sulfonamide functionality
should make them stable to enzymes, and hence they, and
related compounds, may have value as enzyme inhibitors,
or as antiproliferative agents. In addition, the sulfon-
amidoglycosylation of D-mannose resulting in glycosides
with the b-manno configuration is an important finding.
Further applications of the selective b-mannosylation will
be reported in due course.
OAc
O
O
O
AcO
AcO
a
a
H2NSO2R
OAc
R
OAc
OAc
O
OAc
O
b
c
AcO
AcO
AcO
AcO
H2NSO2R
c
NH
O
S
O
b
Melting points were recorded using a Buchi Tottoli apparatus and
are uncorrected. 1H and 13C NMR spectra were recorded on a Varian
Mercury 200 spectrometer at 200 MHz and 50 MHz, respectively,
using TMS as the internal standard and CDCl3, MeCN-d3 or
DMSO-d6 as solvent. Elemental analyses were recorded using a
Carlo Erba EA 1108 apparatus. MeCN was distilled from P4O10.
HClO4·SiO2 and HBF4·SiO2 were prepared as described previous-
ly.21,22 Per-O-acetylated sugars were prepared using Ac2O and
HClO4·SiO2 as catalyst and were reacted as anomeric mixtures.13
The reactions were monitored by TLC on Merck silica gel 60 F254
with detection by charring with H2SO4. Flash column chromatogra-
phy was performed on Macherey-Nagel silica gel 60 (230–400
mesh).
d
OAc
OAc
O
H
O
AcO
AcO
N
S
R
O
Scheme 2 Lewis acid promoted sulfonamidoglycosylation of D-
mannose peracetate
Although it can be suggested that the proposed epimeriza-
tion is very fast, another possible explanation for the ob-
served selectivity is attack by the sulfonamide on the
positively charged anomeric position without neighboring
group participation. Axial attack would afford the a-iso-
mer (Scheme 2, path c) while attack from the equatorial
position would give the b-isomer (Scheme 2, path b). The
b-anomer should be favored as the steric effects present in
the axial isomer are accentuated by an nN→σ*C–O orbital
interaction (exo-anomeric effect). An anti relationship be-
N-Glycosylsulfonamides; General Procedure
BF3·OEt2 (2 equiv) was added dropwise to a vigorously stirred so-
lution of per-O-acetylated sugar (1 mmol) and sulfonamide (2
equiv) in MeCN (4 mL) under an Ar atm. After completion of the
reaction (as indicated by TLC, hexane–EtOAc, 1:1), the reaction
was quenched by the addition of aq NaHCO3 (2 mL) and the mix-
ture was extracted with CH2Cl2 (3 × 5 mL). The combined organic
layers were washed with brine (2 × 5 mL), dried over MgSO4 and
Synthesis 2009, No. 24, 4143–4148 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of Novel N-b-Glycosyl Sulfonamides
4147
the solvent was evaporated. The residue was purified by flash col-
umn chromatography (hexane–EtOAc) and/or by crystallization
(hexane–EtOAc).
13C NMR (50 MHz, CDCl3): d = 171.26 (CH3COO), 170.55
(CH3COO), 170.23 (CH3COO), 170.03 (CH3COO), 83.20 (C-1),
72.44 (C-5), 70.98 (C-4), 67.74 (C-2), 67.32 (C-3), 61.70 (C-6),
50.01 (CH2CH3), 20.97 (CH3COO), 20.80 (2 × CH3COO), 20.71
(CH3COO), 8.21 (CH2CH3).
2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl Ethanesulfonamide
(5)
White needles; mp 149–150 °C.
Anal. Calcd for C16H25NO11S: C, 43.7; H, 5.7; N, 3.2; S, 7.3. Found:
C, 43.8; H, 5.7; N, 3.3; S, 7.2.
1H NMR (200 MHz, CDCl3): d = 5.53 (br d, J = 7.8 Hz, 1 H, NH),
5.91 (t, J = 9.6 Hz, 1 H, H-4), 5.02 (t, J = 9.6 Hz, 1 H, H-3), 4.93 (t,
J = 9.6 Hz, 1 H, H-2), 4.76 (br t, J = 8.4 Hz, 1 H, H-1), 4.17 (d,
J = 3.9 Hz, 2 H, 2 × H-6), 3.76 (dt, J = 10.2, 3.9 Hz, 1 H, H-5), 3.14
(dq, J = 7.5, 1.7 Hz, 2 H, CH2CH3), 2.10 (s, 3 H, CH3COO), 2.07 (s,
3 H, CH3COO), 2.04 (s, 3 H, CH3COO), 2.02 (s, 3 H, CH3COO),
1.37 (t, J = 7.5 Hz, 3 H, CH2CH3).
13C NMR (50 MHz, CDCl3): d = 170.87 (CH3COO), 170.37
(CH3COO), 169.81 (CH3COO), 169.53 (CH3COO), 82.70 (C-1),
73.37 (C-5), 72.45 (C-4), 69.94 (C-2), 68.33 (C-3), 61.84 (C-6),
49.86 (CH2CH3), 20.65 (2 × CH3COO), 20.56 (CH3COO), 20.53
(CH3COO), 8.01 (CH2CH3).
2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl p-Toluenesulfon-
amide (9)
Colorless syrup
1H NMR (200 MHz, CDCl3): d = 7.79 (d, J = 8.3 Hz, 2 H, ArH),
7.28 (d, J = 8.3 Hz, 2 H, ArH), 5.87 (br d, J = 9.8 Hz, 1 H, NH), 5.35
(d, J = 2.4 Hz, 1 H, H-4), 5.05 (m, 2 H, H-2, H-3), 4.78 (br t, J = 9.8
Hz, 1 H, C-1), 4.08 (q, J = 7.1 Hz, 1 H, H-5), 3.88 (m, 2 H, 2 × H-
6), 2.39 (s, 3 H, ArCH3), 2.06 (s, 3 H, CH3COO), 2.01 (s, 3 H,
CH3COO), 1.95 (s, 3 H, CH3COO), 1.94 (s, 3 H, CH3COO).
13C NMR (50 MHz, CDCl3): d = 171.15 (CH3COO), 170.58
(CH3COO), 170.28 (CH3COO), 160.10 (CH3COO), 143.92–126.59
(6 × ArC), 83.33 (C-1), 72.30 (C-5), 71.04 (C-4), 67.93 (C-2), 67.16
(C-3), 61.16 (C-6), 21.71 (ArCH3), 20.82 (2 × CH3COO), 20.74 (2
× CH3COO), 20.71 (2 × CH3COO).
Anal. Calcd for C16H25NO11S: C, 43.7; H, 5.7; N, 3.2; S, 7.3. Found:
C, 43.5; H, 5.9; N, 3.4; S, 7.5.
2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl p-Toluenesulfon-
amide (6)
White needles; mp 119–120 °C.
Anal. Calcd for C21H27NO11S: C, 50.3; H, 5.4; N, 2.8; S, 6.4. Found:
C, 50.3; H, 5.5; N, 2.9; S, 6.2.
1H NMR (200 MHz, CDCl3): d = 7.80 (d, J = 8.5 Hz, 2 H, ArH),
7.29 (d, J = 8.5 Hz, 2 H, ArH), 5.69 (br s, 1 H, NH), 5.29 (t, J = 9.3
Hz, 1 H, H-4), 4.98 (app t, J = 10.0 Hz, 1 H, H-3), 4.86 (m, 2 H, H-
2, H-1), 4.08 (dd, J = 12.3, 4.6 Hz, 1 H, H-6), 3.91 (dd, J = 12.3, 2.5
Hz, 1 H, H-6), 3.67 (ddd, J = 10.0, 4.6, 2.5 Hz, 1 H, H-5), 2.41 (s, 3
H, ArCH3), 2.01 (s, 3 H, CH3COO), 1.99 (s, 3 H, CH3COO), 1.97
(s, 3 H, CH3COO), 1.93 (s, 3 H, CH3COO).
13C NMR (50 MHz, CDCl3): d = 170.80 (CH3COO), 170.57
(CH3COO), 170.00 (CH3COO), 169.62 (CH3COO), 143.96–126.65
(6 × ArC), 83.02 (C-1), 73.62 (C-3), 72.89 (C-5), 70.46 (C-2), 68.50
(C-4), 61.94 (C-6), 21.64 (ArCH3), 20.74 (4 × CH3COO).
2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl Sulfamide (10)
White needles; mp 185–186 °C.
1H NMR (200 MHz, DMSO-d6): d = 7.92 (br d, J = 9.1 Hz, 1 H,
NH), 6.53 (br s, 2 H, NH2), 5.20 (m, 2 H, H-4, H-3), 4.95 (t, J = 9.1
Hz, 1 H, H-2), 4.77 (t, J = 9.1 Hz, 1 H, H-1), 4.08 (m, 3 H, H-5, 2 ×
H-6), 2.07 (s, 3 H, CH3COO), 1.98 (s, 3 H, CH3COO), 1.96 (s, 3 H,
CH3COO), 1.88 (s, 3 H, CH3COO).
13C NMR (50 MHz, DMSO-d6): d = 170.56 (CH3COO), 170.10 (2
× CH3COO), 169.78 (CH3COO), 83.26 (C-1), 71.78 (C-5), 71.60
(C-4), 68.48 (C-2), 67.90 (C-3), 61.44 (C-6), 21.29 (CH3COO),
21.16 (CH3COO), 21.13 (CH3COO), 21.01 (CH3COO).
Anal. Calcd for C21H27NO11S: C, 50.3; H, 5.4; N, 2.8; S, 6.4. Found:
C, 50.1; H, 5.6; N, 2.8; S, 6.7.
Anal. Calcd for C14H22N2O11S: C, 39.4; H, 5.2; N, 6.6; S, 7.5.
Found: C, 39.5; H, 5.4; N, 6.4; S, 7.3.
2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl Sulfamide (7)
2,3,4,6-Tetra-O-acetyl-b-D-mannopyranosyl Methanesulfon-
amide (11)
White needles; mp 169–171 °C.
White needles; mp 161–162 °C.
1H NMR (200 MHz, MeCN-d3): d = 6.13 (d, J = 9.9 Hz, 1 H, NH),
5.32 (m, 3 H, H-4, NH2), 5.02 (t, J = 9.8 Hz, 1 H, H-3), 4.90 (m, 2
H, H-2, H-1), 4.20 (m, 2 H, 2 × H-6), 3.89 (d, J = 10.1, 3.3 Hz, 1 H,
H-5), 2.04 (s, 3 H, CH3COO), 2.03 (s, 3 H, CH3COO), 2.00 (s, 3 H,
CH3COO), 1.97 (s, 3 H, CH3COO).
13C NMR (50 MHz, MeCN-d3): d = 171.53 (CH3COO), 170.76
(CH3COO), 170.70 (CH3COO), 170.51 (CH3COO), 83.78 (C-1),
73.87 (C-5), 73.57 (C-4), 70.84 (C-2), 69.04 (C-3), 62.51 (C-6),
20.89 (CH3COO), 20.82 (2 × CH3COO), 20.77 (CH3COO).
1H NMR (200 MHz, CDCl3): d = 5.85 (br d, J = 10.5 Hz, 1 H, NH),
5.43 (dd, J = 2.9, 1.3 Hz, 1 H, H-2), 5.10 (m, 2 H, H-4, H-3), 5.03
(dd, J = 10.5, 1.3 Hz, 1 H, H-1), 4.17 (m, 2 H, H-6), 3.73 (m, 1 H,
H-5), 3.08 (s, 3 H, CH3SO2), 2.19 (s, 3 H, CH3COO), 2.06 (s, 3 H,
CH3COO), 2.04 (s, 3 H, CH3COO), 1.96 (s, 3 H, CH3COO).
13C NMR (50 MHz, CDCl3): d = 170.68 (CH3COO), 170.33
(CH3COO), 170.04 (CH3COO), 169.90 (CH3COO), 80.60 (C-1,
JC1–H1 = 156.3 Hz), 74.02 (C-5), 71.51 (C-3), 69.77 (C-2), 65.51 (C-
4), 62.63 (C-6), 43.53 (CH3SO2), 21.04 (CH3COO), 20.94
(CH3COO), 20.89 (CH3COO), 20.69 (CH3COO).
Anal. Calcd for C14H22N2O11S: C, 39.4; H, 5.2; N, 6.6; S, 7.5.
Found: C, 39.2; H, 5.3; N, 6.8; S, 7.4.
Anal. Calcd for C15H23NO11S: C, 42.3; H, 5.5; N, 3.3; S, 7.5. Found:
C, 42.1; H, 5.5; N, 3.5; S, 7.8.
2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl Ethanesulfon-
amide (8)
Colorless syrup.
2,3,4,6-Tetra-O-acetyl-b-D-mannopyranosyl Sulfamide (12)
1H NMR (200 MHz, CDCl3): d = 5.70 (br d, J = 9.9 Hz, 1 H, NH),
5.41 (d, J = 1.0 Hz, 1 H, H-4), 5.13–5.03 (m, 2 H, H-2, H-3), 4.71
(m, 1 H, H-1), 4.09 (m, 2 H, 2 × H-6), 3.98 (dd, J = 5.4, 1.0 Hz, 1
H, H-5), 3.11 (dq, J = 7.3, 1.4 Hz, 2 H, CH2CH3), 2.13 (s, 3 H,
CH3COO), 2.08 (s, 3 H, CH3COO), 2.01 (s, 3 H, CH3COO), 1.97 (s,
3 H, CH3COO), 1.35 (t, J = 7.4 Hz, 3 H, CH2CH3).
White needles; mp 184–185 °C.
1H NMR (200 MHz, DMSO-d6): d = 7.85 (br d, J = 10.2 Hz, 1 H,
NH), 6.57 (br s, 2 H, NH2), 5.26 (dd, J = 9.9, 3.3 Hz, 1 H, H-3), 5.15
(m, 2 H, H-2, H-1), 4.99 (app t, J = 9.9 Hz, 1 H, H-4), 4.20 (dd,
J = 12.1, 4.6 Hz, 1 H, H-6), 4.00 (dd, J = 12.1, 2.2 Hz, 1 H, H-6),
3.86 (m, 1 H, H-5), 2.11 (s, 3 H, CH3COO), 1.98 (s, 6 H, 2 ×
CH3COO), 1.87 (s, 3 H, CH3COO).
Synthesis 2009, No. 24, 4143–4148 © Thieme Stuttgart · New York

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P. A. Colinas et al.
PAPER
13C NMR (50 MHz, DMSO-d6): d = 170.87 (CH3COO), 170.78
(CH3COO), 170.16 (CH3COO), 170.12 (CH3COO), 81.27 (C-1,
JC1–H1 = 156.2 Hz), 72.98 (C-5), 71.70 (C-3), 70.22 (C-2), 66.02 (C-
4), 62.64 (C-6), 21.68 (CH3COO), 21.26 (CH3COO), 21.19
(CH3COO), 21.01 (CH3COO).
(3) Danishefsky’s group reported on the reaction of glycals with
iodonium di-sym-collidine perchlorate and benzenesulfon-
amide to afford 2-b-iodo-1-a-sulfonamidohexose in a
stereoselective manner. These glycosylsulfonamides were
used for the preparation of oligosaccharides containing a 2-
aminohexose subunit. For a review, see: Danishefsky, S. J.;
Bilodeau, M. T. Angew. Chem., Int. Ed. Engl. 1996, 35,
1380.
Anal. Calcd for C14H22N2O11S: C, 39.4; H, 5.2; N, 6.6; S, 7.5.
Found: C, 39.2; H, 5.0; N, 6.8; S, 7.6.
(4) Colinas, P. A.; Bravo, R. D. Org. Lett. 2003, 5, 4509.
(5) Colinas, P. A.; Bravo, R. D. Tetrahedron Lett. 2005, 46,
1687.
(6) Colinas, P. A.; Núñez, N. A.; Bravo, R. D. J. Carbohydr.
Chem. 2008, 27, 141.
(7) Colinas, P. A.; Bravo, R. D. Carbohydr. Res. 2007, 342,
2297.
(8) Rodríguez, O. M.; Colinas, P. A.; Bravo, R. D. Synlett 2009,
1154.
2,3,4,-Tri-O-acetyl-b-L-arabinopyranosyl Methanesulfonamide
(13)
White needles; mp 147–148 °C.
1H NMR (200 MHz, CDCl3): d = 5.75 (br d, J = 9.9 Hz, 1 H, NH),
5.31 (m, 1 H, H-3), 5.10 (m, 2 H, H-4, H-2), 4.69 (ddd, J = 9.9, 5.2,
3.6 Hz, 1 H, H-1), 3.98 (dd, J = 13.5, 2.0 Hz, 1 H, H-5), 3.72 (dd,
J = 13.5, 1.1 Hz, 1 H, H-5), 2.14 (s, 3 H, CH3SO2), 2.08 (s, 3 H,
CH3COO), 2.00 (s, 3 H, CH3COO), 1.95 (s, 3 H, CH3COO).
13C NMR (50 MHz, CDCl3): d = 171.28 (CH3COO), 170.36
(CH3COO), 170.05 (CH3COO), 83.75 (C-1), 70.68 (C-4), 68.18 (C-
3), 68.01 (C-2), 65.88 (C-5), 43.79 (CH3), 21.09 (CH3COO), 20.97
(CH3COO), 20.80 (CH3COO).
(9) Colinas, P. A.; Bravo, R. D.; Vullo, D.; Scozzafava, A.;
Supuran, C. T. Bioorg. Med. Chem. Lett. 2007, 17, 5086.
(10) Alegre, M. L.; Pis Diez, R.; Colinas, P. A. J. Mol. Struct.
2009, 919, 223.
(11) de Bravo, M. G. [INIBIOLP (UNLP-CONICET), Fac. Cs.
Médicas] personal communication.
(12) (a) Davis, B. G. Chem. Rev. 2002, 102, 579. (b) Toshima,
K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503.
(13) Misra, A. K.; Tiwari, P.; Madhusudan, S. K. Carbohydr.
Res. 2005, 340, 325.
Anal. Calcd for C12H19NO9S: C, 40.8; H, 5.4; N, 4.0; S, 9.1. Found:
C, 40.6; H, 5.5; N, 4.2; S, 9.3.
2,3,4,-Tri-O-acetyl-b-L-arabinopyranosyl Sulfamide (14)
Colorless syrup.
1H NMR (200 MHz, DMSO-d6): d = 6.70 (br d, J = 9.5 Hz, 1 H,
NH), 6.57 (br s, 2 H, NH2), 5.12 (m, 2 H, H-3, H-4), 4.95 (m, 1 H,
H-2), 4.69 (br t, J = 9.5 Hz, 1 H, H-1), 4.2 (m, 1 H, H-5), 3.80 (br s,
1 H, H-5), 2.02 (s, 3 H, CH3COO), 1.98 (s, 3 H, CH3COO), 1.90 (s,
3 H, CH3COO).
13C NMR (50 MHz, DMSO-d6): d = 170.54 (CH3COO), 170.18
(CH3COO), 169.87 (CH3COO), 83.56 (C-1), 71.64 (C-4), 68.99 (C-
3), 68.80 (C-2), 65.59 (C-5), 21.47 (CH3COO), 21.35 (CH3COO),
21.14 (CH3COO).
(14) (a) In O-glycosides, the a-anomer has a 1JC1–H1 value of
around 173 Hz, while in the b-series a value of 163 Hz is
typical; see: Bock, K.; Pedersen, C. J. Chem. Soc., Perkin
Trans. 2 1974, 293. (b) b-Thiomannopyranosides have
1JC1–H1 coupling constants of 149–154 Hz while those of the
a-anomers occur at around 166 Hz, see: Crich, D.; Li, H.
J. Org. Chem. 2000, 65, 801.
(15) Rawe, S. L.; Doyle, D.; Zaric, V.; Rozas, I.; McMahon, K.;
Tosin, M.; Bunz, H. M.; Murphy, E. P.; O’Boyle, K. M.;
Murphy, P. V. Carbohydr. Res. 2006, 341, 1370.
(16) Owens, J. M.; Yeung, B. K. S.; Hill, D. C.; Petillo, P. A.
J. Org. Chem. 2001, 66, 1484.
Anal. Calcd for C11H18N2O9S: C, 37.3; H, 5.1; N, 7.9; S, 9.1. Found:
C, 37.3; H, 5.0; N, 7.7; S, 9.2.
(17) An open-chain anomerization mechanism was also proposed
as an explanation for the stereoselectivity in the Lewis acid
catalysed reactions of peracetylated sugars with MeCN to
afford N-b-D-glycosyl amides, see: Song, X.; Hollingsworth,
R. I. Synlett 2006, 3451.
Acknowledgment
The authors are grateful to CONICET (PIP 5710), UNLP, CICPBA
for financial help and Dr. Rubén S. Rimada for the NMR measure-
ments. C.A.T. is the holder of a CONICET fellowship. P.A.C. is a
member of CIC of CONICET.
(18) 1H and 13C NMR spectra of the crude reaction mixtures
showed only the presence of b-sulfonamidomanno-
pyranoside and unreacted per-O-acetylated manno-
pyranoside.
References
(19) Batchelor, R. J.; Green, D. F.; Johnston, B. D.; Patrick, B.
O.; Pinto, B. M. Carbohydr. Res. 2001, 330, 421; and
references cited therein.
(20) Aich, U.; Loganathan, D. Carbohydr. Res. 2007, 342, 704.
(21) Chakraborti, A. K.; Gulhane, R. Chem. Commun. 2003,
1896.
(1) Jiménez-Barbero, J.; Lowary, T. Carbohydr. Res. 2007, 342,
1537.
(2) Monsigny, M.; Quétard, C.; Bourgerie, S.; Delay, D.;
Pichon, C.; Midoux, P.; Mayer, R.; Roche, A. C. Biochimie
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(22) Chakraborti, A. K.; Gulhane, R. Tetrahedron Lett. 2003, 44,
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Synthesis 2009, No. 24, 4143–4148 © Thieme Stuttgart · New York