(5-Nitro-2-pyridyl) 1-thio-β-D-glucopyranoside as a stable and reactive acceptor

Article abstract of DOI:10.1016/S0040-4039(00)01765-2

The title compound was synthesised and studied in several glycosylation procedures as an acceptor. Presented experiments indicate its value as a very stable, effective 'latent' glycosylating agent. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01765-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9923–9926
(5-Nitro-2-pyridyl) 1-thio-b- -glucopyranoside as a stable
D
and reactive acceptor
Gabriela Pastuch, Ilona Wandzik* and Wieslaw Szeja
Department of Chemistry, Silesian Technical University, ul. Krzywoustego 8, 44-100 Gliwice, Poland
Received 24 June 2000; revised 28 September 2000; accepted 4 October 2000
Abstract
The title compound was synthesised and studied in several glycosylation procedures as an acceptor.
Presented experiments indicate its value as a very stable, effective ‘latent’ glycosylating agent. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: glycosidation; thioglycosides; dithiocarbamates of 2-deoxysugars.
Among many approaches described in carbohydrate chemistry, thioglycosides1 are very useful
glycosylating agents in oligosaccharide synthesis.2 Frequent use of this class of compounds as
donors and acceptors is due to their ease of preparation and availability of methods for their
activation in the presence of a variety of promoters. To facilitate the synthesis of oligosaccha-
rides, some new chemoselective glycosylation strategies, e.g. the ‘one-pot sequential
glycosylation’3 and ‘active and latent glycosylation’,4 have recently been developed.
The general concept used herein is based on the difference in reactivity of two anomeric
centres of the glycosyl donor and acceptor. The more reactive thioglycoside is a donor. In our
glycosylation strategy several protected thiosugars have been used as donors: methyl 1-thioglu-
cosides (4, 5) and 1-dithiocarbamates of 2-deoxy sugars (6, 7). We looked for an anomeric
substituent of a glycosyl acceptor that was sufficiently stable to withstand protecting group
manipulations and, moreover, inert towards many activation methods, and we turned our
attention to heteroaromatic 1-thioglycosides. Recently, we have reported a new and effective
methodology for the synthesis of thioglycosides via aromatic nucleophilic substitution of
halogen with 1-thiosugar derivatives.5–7 We have found that hetaryl thioglycosides with electron
withdrawing groups in the ring are very stable donors in most glycosylation conditions. Our
initial experiments on the application of 4-nitrophenyl thioglucoside in a ‘latent glycosylation’
strategy show its moderate reactivity even if very reactive glycosyl donors were used. Searching
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01765-2

9924
for a more suitable acceptor with a sufficiently reactive primary hydroxyl group, 5-nitro-2-
pyridyl b-
-thioglucoside 28 was synthesised in a four-step procedure (Scheme 1). Further
D
investigations were directed in order to examine the limitations of this glycosylating agent.
Scheme 1. (A) MeONa, MeOH, 95% yield. (B) t-Butyldimethylsilyl chloride, imidazole, DMF, 95% yield. (C) CH2Cl2,
benzoyl chloride, pyridine, 81% yield. (D) Acetonitrile, HBF, 81% yield
In reactions with methanol or di-O-isopropylidene-a- -galactopyranose as glycosyl acceptors,
D
thioglycoside 2 was inert towards typical promoter systems: Ag2O, silver triflate (AgOTf),
trimethylsilyl triflate (TMSOTf), N-iodosuccinimide/catalytic triflic acid (NIS/TfOH) and di-
sym-collidine perchlorate (IDCP). Next, coupling reactions of 2 with several glycosyl donors,
presented in Scheme 2, were carried out using the above activators. In every case, the
glycosylation reaction proceeded smoothly, affording the corresponding disaccharides 8–1112 in
good yields with moderate to high stereoselectivity. Results of our experiments are collected in
Table 1.
Scheme 2.
Donor 39 was prepared to show the usefulness of acceptor 2 in a typical Koenigs–Knorr
procedure, donors 410 and 511 show its application in the ‘armed and disarmed’ glycosylation
method. Thus, treatment of per-O-acetylated donor 4 with acceptor 2 in the presence of
appropriate promoter gave disaccharide 812 as the b anomer, while reaction between 2 and 5
gave disaccharide 912 as a mixture of anomers (Table 1, entry 2 and 3).

9925
Table 1
Glycosylation reactions of 3–7 with 2
Entry
Donor
Promoter
Reaction conditions
solvent/temperature
Reaction
time
Product
Yield
(%)
a:b
1
2
3
4
5
6
7
8
9
3
4
5
6
6
6
6
6
6
7
7
7
Ag2O
Toluene/rt
Toluene/rt
Toluene/rt
Toluene/rt
Toluene/−25°C
Toluene/−25°C
Toluene/rt
Toluene/rt
Toluene/rt
24 h
2 h
1 h
8
8
9
62
82
85
67
81
78
94
93
92
71
95
92
Only b
Only b
2:1
4:1
9:2
5:1
6:1
9:2
3:2
NIS/TfOH
NIS/TfOH
AgOTf
5 min
15 min
15 min
1 h
25 min
50 min
25 min
25 min
45 min
10
10
10
10
10
10
11
11
11
AgOTf
TMSOTf
BF3·Et2O
NIS/TfOH
IDCP
AgOTf
TMSOTf
BF3·Et2O
10
11
12
Toluene/−25°C
Toluene/−25°C
Toluene/rt
15:1
15:1
16.5:1
Other model donors, dithiocarbamates 6 and 7,13 were prepared to examine the effect of
various promoters and temperature on stereoselectivity of the glycosylation reactions. The yields
of the thiodisaccharides 10 and 1112 varied from 67 to 95% depending on the method applied.
Decreasing temperature always gave better yields but did not interfere with the stereoselectivity.
Concerning the effect of promoters, the best result was observed when BF3·Et2O was used. All
examples collected in Table 1 confirm the extreme stability of acceptor 2 under the conditions
tested.
Acknowledgements
Financial support from the Polish State Committee for Scientific Research (Grant No. 3
T09A 105 15).
References
1. Garegg, P. J. Adv. Carbohydr. Chem. Biochem. 1997, 52, 179 and references cited therein.
2. For a recent review articles on oligosaccharide synthesis see: Paulsen, H. Angew. Chem., Int. Ed. Engl. 1990, 29,
823; Toshima, K.; Tatsua, K. Chem. Rev. 1993, 93, 1503; Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem.
Biochem. 1994, 50, 21; Danishefsky, S. J.; Bilodeau, M. T. Angew. Chem., Int. Ed. Engl. 1996, 35, 1380.
3. Zhang, Z.; Ollmann, I. R.; Ye, X. S.; Wischnat, R.; Beasov, T.; Wong, C. H. J. Am. Chem. Soc. 1999, 121, 734.
4. Roy, R.; Andersson, F. O.; Letellier, M. Tetrahedron Lett. 1992, 33, 6053.
5. Driguez, H.; Szeja, W. Synthesis 1994, 1413.
6. Przybysz, B.; Szeja, W.; Walczak, K.; Suwinski, J. Pol. J. Chem. 1997, 71, 1421.
7. Pastuch, G.; Szeja, W. Carbohydr. Lett. 1997, 2, 281.
8. (5-Nitro-2-pyridyl) 2,3,4-tri-O-benzoyl-1-thio-i-
D
-glucopyranoside 2: mp=60–62°C; [h]=132.7 (c 0.6, CHCl3),
1H NMR (300 MHz) l 1.22 (s, 1H, 6-OH), 3.73 (dd, 1H, J6,5=4.6 Hz, J6,6a=12.9 Hz, H-6), 3.86 (dd, 1H,
J
J
6a,5=2.2 Hz, J6a,6=12.9 Hz, H-6a), 4.03 (ddd, 1H, J5,4=10.2 Hz, J5,6=4.6 Hz, J5,6a=2.2 Hz, H-5), 5.59 (dd, 1H,
4,3=9.8 Hz, J4,5=10.2 Hz, H-4), 5.75 (dd, 1H, J2,3=9.5 Hz, J2,1=10.5 Hz, H-2), 6.13 (dd, 1H, J3,2=9.5 Hz,

9926
J3,4=9.8 Hz, H-3), 6.26 (d, 1H, J1,2=10.5 Hz, H-1), 7.25–7.61 (m, 10H, Ph, H-3ar), 7.82–7.92 (m, 6H, Ph), 8.25
(dd, 1H, J4ar,6ar=2.6 Hz, J4ar,3ar=8.8 Hz, H-4ar), 9.28 (d, 1H, H-6ar).
9. Lemieux, R. V. In Methods in Carbohydrate Chemistry; Whistler, R. L.; Wolfrom, M. L., Eds.; Academic Press:
New York, 1963; Vol. 2, p. 221.
10. Cerny´, M.; Paca´k, J. Collect. Czech. Chem. Commun. 1959, 24, 2566.
11. Ito, Y.; Ogawa, T. Tetrahedron Lett. 1987, 28, 4701.
1
12. All new compounds gave satisfactory H NMR (300 MHz) spectroscopic and elemental analytical data. Selected
data: 8: (5-Nitro-2-pyridyl) 2,3,4,6-tetra-O-acetyl-i-D-glucopiranosyl-(1“6)-2,3,4-tri-O-benzoyl-1-thio-i-D-glu-
1
copyranoside: syrup, [h]=97.8 (c 0.3, CHCl3), H NMR l 1.95, 1.97, 1.98, 2.01 (4s, 12H, 4×CH3CO), 3.52 (m,
1H, H-5%), 3.78 (dd, 1H, J6,5=6.3 Hz, J6,6a=11.5 Hz, H-6), 4.01 (dd, 1H, J6a,5=1.7 Hz, J6a,6=11.5 Hz, H-6a),
4.03 (dd, 1H, J6a%,5%=2.2 Hz, J6a%,6%=12.2 Hz, H-6a%), 4.17 (dd, 1H, J6%,5%=4.9 Hz, J6%,6a%=12.2 Hz, H-6%), 4.23 (m,
1H, H-5), 4.54 (d, 1H, J1%,2%=7.3 Hz, H-1%), 4.89–5.0 (m, 3H, H-2%, H-3%, H-4%), 5.49 (dd, 1H, J4,5=9.8 Hz,
J
4,3=9.8 Hz, H-4), 5.69 (dd, 1H, J2,3=9.8 Hz, J2,1=9.8 Hz, H-2), 6.02 (dd, 1H, J3,4=9.5 Hz, J3,2=9.8 Hz, H-3),
6.16 (d, 1H, J1,2=9.8 Hz, H-1), 7.25–7.57 (m, 9H, Ph, H-3ar), 7.79–7.94 (m, 7H, Ph, H-3ar), 8.31 (dd, 1H,
4ar,6ar=2.6 Hz, J4ar,3ar=8.8 Hz, H-4ar), 9.31 (d, 1H, H-6ar). 9: (5-Nitro-2-pyridyl) 2,3,4,6-tetra-O-benzyl- -glu-
-glucopyranoside: syrup, H NMR (a anomer) l 3.44–3.51 (m,
J
D
1
copiranosyl-(1“6)-2,3,4-tri-O-benzoyl-1-thio-i-
D
4H, H-2%, H-5%, H-6, H-6%), 3.64 (dd, 1H, J6a,5=2.4 Hz, J6a,6=11.2 Hz, H-6a), 3.66–3.75 (m, 2H, H-5, H-6a%), 3.86
(dd, 1H, J4%,5%=8.1 Hz, J4%,3%=8.2 Hz, H-4%), 4.33 (dd, 1H, J3%,2%=8.2 Hz, J3%,4%=8.2 Hz, H-3%), 4.25, 4.52 (AB, 2H,
J=10.5 Hz, CH2Ph), 4.41, 4.60 (AB, 2H, J=12.0 Hz, CH2Ph), 4.61, 4.76 (AB, 2H, J=12.2 Hz, CH2Ph), 4.70,
4.93 (AB, 2H, J=10.7 Hz, CH2Ph), 4.65 (d, 1H, J1%,2%=3.7 Hz, H-1%), 5.51 (dd, 1H, J4,5=9.8 Hz, J4,3=9.3 Hz,
H-4), 5.67 (dd, 1H, J2,3=9.5 Hz, J2,1=10.5 Hz, H-2), 6.03 (dd, 1H, J3,4=9.3 Hz, J3,2=9.5 Hz, H-3), 6.04 (d, 1H,
J1,2=10.5 Hz, H-1), 6.87–6.90 (m, 2H, Ph), 6.99 (d, 1H, J3ar,4ar=8.8 Hz, H-3ar), 7.18–7.39 (m, 28H, Ph),
7.79–7.97 (m, 6H, Ph, H-4ar), 9.17 (d, 1H, J6ar,4ar=2.4 Hz, H-6ar). (b anomer) l 3.31–3.39 (m, 2H, H-2%, H-5%),
3.45–3.60 (m, 5H, H-5, H-6, H-6%, H-6a, H-6a%), 3.82 (dd, 1H, J4%,5%=8.2 Hz, J4%,3%=8.1 Hz, H-4%), 4.15 (d, 1H,
J1%,2%=10.9 Hz, H-1%), 4.26, 4.42 (AB, 2H, J=10.5 Hz, CH2Ph), 4.36, 4.47 (AB, 2H, J=12.2 Hz, CH2Ph), 4.38
(dd, 1H, J3%,4%=8.1 Hz, J3%,2%=8.1 Hz, H-3%), 4.62, 4.77 (AB, 2H, J=10.7 Hz, CH2Ph), 4.64, 4.75 (AB, 2H, J=10.7
Hz, CH2Ph), 5.51 (dd, 1H, J4,5=9.8 Hz, J4,3=9.4 Hz, H-4), 5.73 (dd, 1H, J2,3=9.4 Hz, J2,1=10.5 Hz, H-2), 6.07
(dd, 1H, J3,4=9.4 Hz, J3,2=9.4 Hz, H-3), 6.23 (d, 1H, J1,2=10.5 Hz, H-1), 6.91–7.01 (m, 3H, Ph), 7.10–7.45 (m,
25H, Ph, H-3ar), 7.79–7.95 (m, 9H, Ph, H-4ar), 9.04 (d, 1H, J6ar,4ar=2.4 Hz, H-6ar). 10: (5-Nitro-2-pyridyl)
2-deoxy-3,4-di-O-benzyl-
NMR l 1.09 (d, J=6.2 Hz, CH3(H-6%b)), 1.15 (d, J=6.0 Hz, CH3(H-6%a)), 1.39 (m, H-2%axb), 1.56 (ddd,
2%ax,2%eq=12.9 Hz, J2%ax,3%=10.0 Hz, H-2%axa), 2.04 (m, H-2%eqb), 2.29 (ddd, J2%eq,3%=4.9 Hz, H-2%eqa), 2.99 (dd,
L-rhamnopyranosyl-(1“6)-2,3,4-tri-O-benzoyl-1-thio-i-D
-glucopyranoside: syrup, 1H
J
J4%,5%=9.0 Hz, H-4%b), 3.07 (dd, J4%,5%=9.2 Hz, J4%,3%=4.6 Hz, H-4%a), 3.19 (dd, J6,5=6.4 Hz, J6,6a=9.5 Hz, H-6b),
3.43–3.54 (m, H-5%b, H-6ab), 3.61 (dd, J6,6a=12.0 Hz, J6,5=5.6 Hz, H-6a), 3.70 (dq, J5%,4%=9.3 Hz, H-5%a), 3.80
(dd, J6a,5=2.4 Hz, J6a,6=12.0 Hz, H-6aa), 3.88 (ddd, J3%,4%=4.6 Hz, H-3%a), 4.01 (m, H-3%b), 4.13 (m, H-5b), 4.15
(ddd, J5,6a=2.4 Hz, J5,6=5.6 Hz, J5,4=10.0 Hz, H-5a), 4.34 (dd, J1%2%eq=0.8 Hz, J1%2%ax=8.3 Hz, H-1%b), 4.43, 4.50
(AB, J=12.0 Hz, CH2Phb), 4.55, 4.59 (AB, J=11.4 Hz, CH2Pha), 4.57, 4.88 (AB, J=10.7 Hz, CH2Phb), 6.63,
4.94 (AB, J=11.4 Hz, CH2Pha), 4.75 (d, J1%,2%ax=2.9 Hz, H-1%a), 5.65 (dd, J4,5=10.0 Hz, J4,3=9.5 Hz, H-4a),
5.66 (dd, J4,5=10.0 Hz, J4,3=9.3 Hz, H-4b), 5.72 (dd, J2,3=9.9 Hz, J2,1=10.6 Hz, H-2b), 5.74 (dd, J2,3=9.5 Hz,
J2,1=10.5 Hz, H-2a), 6.02 (dd, J3,4=9.3 Hz, J3,2=9.9 Hz, H-3b), 6.03 (dd, J3,4=9.5 Hz, J3,2=9.5 Hz, H-3a), 6.18
(d, J1,2=10.5 Hz, H-1a), 6.22 (d, J1,2=10.6 Hz, H-1b), 7.32–7.95 (m, Ph, H-3ara, H-3arb), 7.81–7.95 (m, Ph), 8.19
(dd, J4ar,3ar=8.7 Hz, J4ar,6ar=2.4 Hz, H-4arb), 8.20 (dd, J4ar,6ar=2.4 Hz, J4ar,3ar=8.7 Hz, H-4ara), 9.28 (d,
J
4ar,6ar=2.7 Hz, H-6arb), 9.32 (d, H-6ara). 11: (5-Nitro-2-pyridyl) 2-deoxy-3,4,6-tri-O-benzyl-
D
-galactopyranosyl-
1
(1“6)-2,3,4-tri-O-benzoyl-1-thio-i-
D
-glucopyranoside: syrup, H NMR l 1.86 (ddd, 1H, J2%eq,1%:0 Hz, J2%eq,3%
=
4.6 Hz, J2%eq,2%ax=12.4 Hz, H-2e%q), 2.12 (ddd, 1H, J2%ax,3%=12.0 Hz, J2%ax,2%eq=12.4 Hz, J2%ax,1%=3.4 Hz, H-2a%x),
3.34–3.36 (m, 2H, H-6, H-5%), 3.66 (dd, 1H, J6a,5=3.1 Hz, J6a,6=11.3 Hz, H-6a), 3.70–3.89 (m, 4H, H-4%, H-5,
H-6%, H-6a%), 4.17 (m, 1H, H-3%), 4.20, 4.26 (AB, 2H, J=11.9 Hz, CH2Ph), 4.51 (s, 2H, CH2Ph), 4.53, 4.86 (AB,
2H, J=11.5 Hz, CH2Ph), 4.96 (d, 1H, J1%,2%ax=3.4 Hz, H-1%), 5.74 (dd, 1H, J2,3=9.8 Hz, J2,1=10.4 Hz, H-2), 5.75
(dd, 1H, J4,5=10.4 Hz, J4,3=9.5 Hz, H-4), 6.03 (dd, 1H, J3,4=9.5 Hz, J3,2=9.8 Hz, H-3), 6.20 (d, 1H, J1,2=10.4
Hz, H-1), 7.14–7.38 (m, 25H, Ph, H-3ar), 7.82–7.85 (m, 6H, Ph), 8.10 (dd, 1H, J4ar,3ar=8.7 Hz, J4ar,6ar=2.4 Hz,
H-4ar), 9.23 (d, 1H, J6ar,4ar=2.4 Hz, H-6ar).
13. Wandzik, I.; Szeja, W. Pol. J. Chem. 1998, 72, 703.
.