Sulfonamidoglycosylation of methyl glycosides employing perchloric acid supported on silica gel

Article abstract of DOI:10.1080/07328300802030829

The sulfonamidoglycosylation of methyl glycosides in the presence of perchloric acid immobilized on silica gel proceeded effectively to afford the corresponding sulfonamido glycosides with good to high yields with minimal workup and short reaction times.

Full text of DOI:10.1080/07328300802030829

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Sulfonamidoglycosylation of Methyl
Glycosides Employing Perchloric Acid
Supported on Silica Gel
Pedro A. Colinas a , Nicolás A. Núñez a & Rodolfo D. Bravo a
a LADECOR, Departamento de Química , Facultad de Ciencias Exactas,
Universidad Nacional de La Plata , La Plata , Argentina
Published online: 12 Jun 2008.
To cite this article: Pedro A. Colinas , Nicolás A. Núñez & Rodolfo D. Bravo (2008) Sulfonamidoglycosylation
of Methyl Glycosides Employing Perchloric Acid Supported on Silica Gel, Journal of Carbohydrate Chemistry,
27:3, 141-147, DOI: 10.1080/07328300802030829
To link to this article: http://dx.doi.org/10.1080/07328300802030829
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Journal of Carbohydrate Chemistry, 27:141–147, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300802030829
Sulfonamidoglycosylation
of Methyl Glycosides
Employing Perchloric Acid
Supported on Silica Gel
´
´
Pedro A. Colinas, Nicolas A. Nun˜ez, and Rodolfo D. Bravo
´
LADECOR, Departamento de Quımica, Facultad de Ciencias Exactas, Universidad
Nacional de La Plata, La Plata, Argentina
The sulfonamidoglycosylation of methyl glycosides in the presence of perchloric acid
immobilized on silica gel proceeded effectively to afford the corresponding sulfonamido
glycosides with good to high yields with minimal workup and short reaction times. This
methodology was applied to the synthesis of some N-glycosyl sulfamides, which showed
low nanomolar activity against human carbonic anhydrase.
Keywords Sulfonamidoglycosylation, Methyl glycosides, Perchloric acid-silica
Sulfonamides, which have been clinically used for many years, have been found
to possess a large number of different biological activities, including antibacter-
ial, antiviral, antidiabetic, diuretic, and antithyroid activities.[1] They exert
their diverse pharmacological effects by interacting with a wide range of differ-
ent cellular targets.
In the development of new chemotherapeutic agents, several sulfonamides
have emerged as useful therapeutics for the treatment of cancer. E7010,[2]
E7070,[2] ABT751,[3] and T138067[4] have been found to be inhibitors of
tumor cell proliferation and some of them are under clinical evaluation and
will soon be launched as antitumor drugs (Fig. 1). The mechanism of antitumor
action of these compounds has been studied in detail and they inhibit
Received August 28, 2007; accepted November 5, 2007.
´
Address correspondence to Pedro A. Colinas, LADECOR, Departamento de Quımica,
Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115 (1900) La
Plata, La Plata, Argentina. E-mail: pcolinas@quimica.unlp.edu.ar
141

P. A. Colinas et al.
142
Figure 1: Antimitotic sulfonamides.
microtubule assembly by binding to tubulin at the colchicine binding site.[5]
Other sulfonamides possessing a free sulfonamido moiety probably act as
strong carbonic anhydrase inhibitors.[6] It was found that isozyme CA IX is
overexpressed in a variety of tumor types and plays an important role in the
growth and survival of tumor cells.[7] Thus, their inhibition is the target for
the development of novel antitumor therapies.
Only few reports described the synthesis of sulfonamidoglycosides.
Danishefsky’s group reported on the reaction of glycals with iodonium di-
sym-collidine perchlorate and benzenesulfonamide to afford stereoselectively
2-b-iodo-1-a-sulfonamidohexoses.[8] This class of glycosylsulfonamides were
used for the preparation of oligosaccharides with the 2-aminohexose
subunit.[9] Recently we reported on the stereoselective synthesis of glycosylsul-
fonamides via sulfonamidoglycosylation of benzylated glycals using a catalytic
amount of triphenylphosphine hydrobromide.[10] The novel method afforded
the b-sulfonamidoglycosides with good to high yields. Later on we developed
a novel approach to ribofuranosylsulfonamides using the reaction of methyl
glycosides with sulfonamides in the presence of boron trifluoride etherate.[11]
Some of the glycosylsulfonamides prepared by us showed antiproliferative
activity against the human hepatocellular carcinoma in the micromolar
range.[10] Unfortunately, our last developed methodology has an important
drawback: boron trifluoride etherate is a highly toxic reagent. This prompted
us to initiate studies designed to provide an environmentally friendlier route
for the synthesis of sulfonamidoribofuranosides. It seems very interesting to
study the use of acids supported on silica gel to promote the sulfonamidoglyco-
sylations. The application of heterogeneous catalysts such as inorganic acids in
organic synthesis is an attractive area of research.[12] Noting recent reports of
the use of perchloric acid supported on silica gel[13] as an inexpensive, nontoxic,
and recyclable catalyst for various organic transformations, affording the cor-
responding products in excellent yields with high selectivity,[14] we decided to
investigate HClO4-SiO2 in the sulfonamidoglycosylations.

Sulfonamidoglycosylation of Methyl Glycosides
143
Scheme 1: Reagents and conditions: (i) HClO4-SiO2, r t, CH2Cl2.
Now we wish to report that perchloric acid supported on silicagel (HClO4-
SiO2 was prepared as described previously,[13] except it was dried for 2 h at
1108C.) allows the reaction of methyl glycosides with sulfonamides to give
the corresponding sulfonamidoglycosides in good to high yields and in short
reaction times. Further, no precautions need to be taken to exclude air from
the reaction medium and the method requires minimal workup.
We first turned our attention to the conditions of sulfonamidoglycosylation
using methyl tri-O-benzyl-D-ribofuranoside (1) and p-toluenesulfonamide
(Sch. 1). (General procedure: To a solution or suspension of the methyl glyco-
side (1 mmol), the sulfonamide (1.5 sulfonamide) in 5 mL of dry methyle-
nechloride was added 1.3 g of HClO4-SiO2 at rt. After stirring for the time
indicated, the reaction mixture was filtered through Celite and the solvent
was removed in vacuo. The residue was chromatographed on silica gel
(eluent hexane/ethyl acetate) and/or crystallized (ethyl acetate/hexane) to
afford the sulfonamidoglycosides.) The results are summarized in Table 1.
Table 1: Reaction of p-toluenesulfonamide with methyl 2,3,4-tri-O-
benzylribofuranoside 1 in CH2Cl2 at room temperaturea,b
.
Sulfonamide
(equiv.)
Time
(min)
Entry
Promoter
Ratio a:b
Yield (%)
1
2
3
2
1.5
1.2
HClO4-SiO2 (1.3 g)
HClO4-SiO2 (1.3 g)
HClO4-SiO2 (1.3 g)
5
5
5
30
30
120
30
120
5
43:57
45:55c
40:60
42:58
45:55
45:55
43:57
45:55
40:60
—
92
90d
60
58
18
25
78
72
54
4
5
1.5
1.5
HClO4-SiO2 (0.65 g)
HClO4-SiO2 (1.0 g)
6
7
8
1.5
1.5
1.5
HClO4-SiO2 (1.9 g)
HBF4-SiO2 (1.3 g)
SiO2 (1.3 g)
120
120
No reaction
No reaction
—
aAll the reactions were performed using 1 mmol of the methyl glycoside.
bAnomeric ratios were determined by 1H NMR spectroscopy.
cLit. 43:57. Ref. [11].
dLit 85%. Ref. [11].

P. A. Colinas et al.
144
Scheme 2: Reagents and conditions: (i) HClO4-SiO2, rt, CH2Cl2.
The use of higher quantities of the HClO4-SiO2 only led to lower yields
(entry 6) and they were not improved by using higher quantities of the sulfona-
mide (entry 1). The results showed that tetrafluorboric acid was not effective
for catalyzing the sulfonamidoglycosylation reactions (entry 7). The addition
of molecular sieves, as is mentioned in our previous report,[11] was not necess-
ary. The generated methanol was probably removed by the silica gel from the
reaction system.
With this knowledge in hand, the selected conditions were applied to a
variety of sulfonamides and methyl glycosides to analyze the scope of our meth-
odology (Sch. 2). The results are shown in Table 2. The anomeric ratios were
1
determined by H NMR of the reaction mixture.
The products were easily purified by flash chromatography. The 1H and 13
C
NMR and 2D COSY experiments and mass spectral data of the sulfonamides
were in full accordance with their structure.
The results shown in Table 2 indicated additional applications of the new
procedure. Thus, hindered sulfonamides were also effectively coupled to the
methyl ribofuranosides (entries 3 and 4). However, a sulfonamide with higher
Table 2: Reaction of sulfonamides with methyl glycosidesa.
Methyl
glycoside
Time
(min)
Entry
Sulfonamide
Benzyl
Ratio a:bb,c
Yield (%)c
1
2
3
4
5
6
7
8
1
1
1
1
1
2
3
4
5
5
10
10
10
5
45:55 (46:54)
50:50 (48:52)
40:60 (40:60)
50:50 (50:50)
47:53 (45:55)
45:55 (40:60)
1:99
92 (84)
97 (85)
89 (74)
78 (64)
15 (16)
Ethane
N-Methyl-p-toluene
N-Butylbenzyl
N-Isopropyl-p-toluene
p-Toluene
p-Toluene
p-Toluene
95 (75)
5
5
97 (80, 87d )
98 (82, 80d )
1:99
aAll the reactions were performed in CH2Cl2 using 1.3 g of HClO4-SiO2 and 1.5 equiv. of sulfo-
namide at rt.
bAnomeric ratios were determined by 1H NMR spectroscopy.
cRatios and yields previously reported are shown between parenthesis (Ref. 11).
dRef. [10].

Sulfonamidoglycosylation of Methyl Glycosides
145
Scheme 3: Reagents and conditions: i) HClO4-SiO2, rt, CH3CN.
steric hindrance afforded a poor yield of the glycosylsulfonamide (entry 5). The
methodology was also applied to methyl glycopyranosides to furnish the corre-
sponding sulfonamidoglycosides in excellent yields (entries 7 and 8).
The stereochemical outcome was in accordance with the results previously
described by us[10,11] and no influence of the promoter in the anomeric selectiv-
ity was found.
Very recently we have prepared a series of glycosylated sulfamides, which
showed low nanomolar activity against human carbonic anhydrase.[15] The
HClO4-SiO2 was applied to the synthesis of some of these N-glycosylsulfamides
(Sch. 3). The results are shown in Table 3.
Table 3: Reaction of sulfamide with methyl glycosidesa.
Methyl
glycoside
Entry
Time (min)
Product
Ratio a:bb
Yield (%)
1
2
3
4
5
1
3
4
5
6
5
5
5
10
10
11
12
13
14
15
50:50
1:99
6:94
5:95
8:92
82
95
94
90
92
aAll the reactions were performed in CH3CN using 1.3 g of HClO4-SiO2 and 3 equiv. of sulfamide
at rt.
bAnomeric ratios were determined by 1H NMR spectroscopy.

P. A. Colinas et al.
146
Scheme 4: Reagents and conditions: (i) HClO4-SiO2, r t, CH2Cl2.
Our attention next turned to the reaction of D-glycals with p-toluenesulfo-
namide using HClO4-SiO2. The addition reaction afforded the O-glycosides (17)
in poor yields (Sch. 4). (The reactions were performed in methylenechloride
using 0.05 equiv of HClO4-SiO2 and 1.2 equiv. of sulfonamide. Higher quan-
tities of the promoter or the sulfonamide showed no effect on the yields
(10%–14%)). Similar results using boron trifluoride etherate as catalyst were
described by us.[10] The formation of this product could be explained by the
reaction of sulfonamide with the carbenium ion at C(3) followed by the
addition of the benzyl alcohol to the double bond.
In summary, our present methodology has the following advantages: (a) the
promoter is an inexpensive noncorrosive powder, (b) the workup required only
filtration of the promoter followed by flash chromatography, and (c) there were
short reaction times (in order of minutes) and good to high yields. In conclusion,
we have developed a mild and eco-friendly approach for the sulfonamid-
oglycosylation of methyl glycosides to afford the corresponding N-glycosyl
sulfonamides. To the best of our knowledge, it is the first report of a sulfonami-
doglycosylation promoted by a heterogenous reagent.
ACKNOWLEDGMENTS
The authors wish to thank CIC (Pcia de Buenos Aires) for financial support and
´
Dr. Agustın Ponzinibbio for NMR measurements. P.A.C. is member of CIC of
CONICET (Argentina).
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