A concise synthesis of arabinogalactan with β-(1→6) galactopyranose backbone and α-(1→2) arabinofuranose side chains

Article abstract of DOI:10.1016/j.tetlet.2003.08.087

Penta- and octasaccharides composed of β-(1→6)-linked galactose backbone with α-(1→2)-linked arabinose branches were synthesized through coupling of α-(1→5)-linked arabinofuranosyl disaccharide donor with a tri- and tetrasaccharide backbone at C-2, respectively.

Full text of DOI:10.1016/j.tetlet.2003.08.087

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8325–8329
A concise synthesis of arabinogalactan with b-(1“6)
galactopyranose backbone and a-(1“2) arabinofuranose
side chains
Ying Zeng, Aixiao Li and Fanzuo Kong*
Research Center for Eco-Environmental Sciences, The Chinese Academy of Sciences, PO Box 2871, Beijing 100085, PR China
Received 26 May 2003; revised 30 July 2003; accepted 4 August 2003
Abstract—Penta- and octasaccharides composed of b-(1“6)-linked galactose backbone with a-(1“2)-linked arabinose branches
were synthesized through coupling of a-(1“5)-linked arabinofuranosyl disaccharide donor with a tri- and tetrasaccharide
backbone at C-2, respectively.
© 2003 Elsevier Ltd. All rights reserved.
Arabinogalactans (AGs) widely distribute in plant cell
walls1,2 and they complex with protein to form glyco-
protein¯proteoglycan (AGPs).3 AGPs play important
roles in cell differentiation and development, as defense
systems in plants, and are involved in cell–cell interac-
tions and elongation growth of the cell wall.4 And
many AGPs have biological activities, such as
immunomodulating activity,5 anti-complement activ-
ity;6 reticuloendothelial system activating properties,7
and many other activities.8 The arabinogalactans with
b-(1“6)-linked galactopyranose backbone and a-(1“
2)-linked arabinofuranose side chains such as 19 and 20
may exist in Echinacea purpurea which have
immunomodulating activity.5 Although the presence of
2,6-branched residues in AGPs is well defined, the exact
structure of these saccharides remains to be established.
Especially, for elucidation of the molecular structure
responsible for their biological activity, it would be
necessary to synthesize 2,6-branched arabinogalactans
(Scheme 1).
binogalacto-octasaccharide 20 is to prepare first the
b-(1“6)-linked trisaccharide acceptor with 2%-OH and
the tetrasaccharide acceptor with 2,2%%-OH, and then to
assemble the arabinofuranose side chains. In our syn-
thesis, we applied benzoyl group as relatively ‘perma-
nent’ group, and acetyl group as temporary group. The
benzoyl and acetyl protecting groups are well differenti-
ated by treating the protected sugars with ꢀ3% solu-
tion of MeCOCl in CHCl3–MeOH,11 which produces
dry HCl in situ, and the acetyl is removed completely.
For syntheses of the tri- and tetrasaccharide backbone,
four simple galactopyranose synthons 1,12 2, 3, and 4
were prepared. Compound 2 was obtained by 6-O-trityl-
ation of galactose, benzoylation, acetolysis, 1-O-
deacetylation, and trichloroacetimidation. Compound 3
was obtained by 6-O-tritylation of 1,2-O-ethylidene-a-
D
-galactopyranose, benzoylation, acetolysis, 1-O-
deacetylation, trichloroacetimidation, and coupling
with 4-methoxyphenol. Compound 4 was obtained by
condensation of 2 with 4-methoxyphenol. Our initial
attempt was to deacetylate 3 with MeCOCl/CH3OH/
CH2Cl2 (1:25:25) to provide 5. However, it was found
that even when the reaction was run at room tempera-
ture for 10 h, the required 2,6-OH derivative 5 was
obtained in only 40% yield together with the byproduct
6 (30%), and the reaction mixture was difficult to be
separated. So, our focus turned to prepare 6 by selec-
tive 6-O-deacetylation under much milder acidic condi-
Until now, very few examples exist on the chemical
synthesis of the arabinogalactans.9,10 We present herein
a facile synthesis of penta- and octasaccharides com-
prised of b-(1“6)-linked galactose backbone with a-
(1“2)-linked arabinose side chains.
Retrosynthetic analysis indicated that the best way to
obtain the arabinogalacto-pentasaccharide 19 and ara-
tions. For this purpose,
3
was dissolved in
MeCOCl/CH3OH/CH2Cl2 (1:500:500), and the mixture
was stirred at room temperature for 12 h, leading to
acceptor 6 in excellent yield (88%), without affecting
the 2-O-acetyl group. This seems to be a fine method to
Keywords: synthesis; arabinogalactan; oligosaccharide.
* Corresponding author.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.087

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Y. Zeng et al. / Tetrahedron Letters 44 (2003) 8325–8329
Scheme 1. Reagents and conditions: (a) MeCOCl/CH3OH/CH2Cl2 (1:25:25), 10 h; (b) MeCOCl/CH3OH/CH2Cl2 (1:500:500), 12 h,
6, 88%; 7, 90%; 11, 85%; (c) TMSOTf, CH2Cl2, N2, −20°C to rt, 4 h, 8, 83%; 9, 79%; 12, 77%; 13, 75%; (d) CAN, H2O/CH3CN,
0.5 h, then CCl3CN, DBU, CH2Cl2 (dry), 10 h, 10, 66% two steps; (e) MeCOCl/CH3OH/CH2Cl2 (1:50:50), 48 h, 14, 87%; 15, 80%.
ation of disaccharides. Oxidative cleavage of 1-OMP of
8 with CAN (4.5 equiv.) in CH3CN–H2O (4:1 v/v)
followed by trichloroacetimidation with trichloroace-
tonitrile and DBU in dry dichloromethane gave the
disaccharide donor 10 (71%).
differentiate galactose primary hydroxyl acetate from
the secondary one. Compound 4 was also deacetylated
under the same reaction conditions to give acceptor 7.
Condensation of the donors 1, and 2 with the acceptor
6 in the presence of TMSOTf as catalyst afforded
exclusively b-(1“6)-linked disaccharide building block
8 (83%) and 9 (79%), respectively. The disaccharide
acceptor 11 with 6%-OH was obtained in a satisfactory
yield (85%) by treatment of 9 with MeCOCl/CH3-
OH/CH2Cl2 (1:500:500), indicating that the mild acidic
conditions were also suitable for selective 6-O-deacetyl-
Coupling of the disaccharide donor 10 with the
monosaccharide acceptor 7 afforded the b-(1“6)-linked
galactose trisaccharide 12 (77%). Similarly, the b-(1“
6)-linked galactose tetrasaccharide 13 was obtained by
coupling donor 10 with the disaccharide acceptor 11 in
good yield (75%). Removal of the 2%-O-acetyl of 12 and

Y. Zeng et al. / Tetrahedron Letters 44 (2003) 8325–8329
8327
Scheme 2. Reagents and conditions: (a). TMSOTf, CH2Cl2, N2, −20°C to rt, 4 h, 17, 72%; 18, 74%; (b). NH3, CH3OH, 19, 95%;
20, 97%.
2-O-, 2%%-O-acetyl of 13 with MeCOCl/CH3OH/CH2Cl2
(1:50:50) for 48 h at room temperature gave the trisaccha-
ride acceptor 14 (87%) and tetrasaccharide acceptor 15
(80%), respectively.
Inthesyntheses, throughsmoothreactionsallcompounds
described here were obtained in satisfactory yields with
easily accessible materials and inexpensive reagents, and
were isolated and identified with 1H, 13C NMR spectra.13
The donor 2,3,5-tri-O-benzoyl-a-
L
-arabinofuranosyl-
In summary, a special strategy particularly suitable for
the preparation of 2,6-branched arabinogalacto-oligosac-
charides has been developed based on trichloroacetimi-
date donors and selective deacetylation.
(1“5)-2,3-di-O-benzoyl-a- -arabinofuranosyl tricho-
L
loroacetimidate 16 was prepared with reference to our
previous report.9b The galacto-acceptors 14 and 15 were
condensed with the arabinofuranose donor 16 to give the
penta-17 (72%) and octasaccharide 18 (74%), respectively.
The fully protected arabinogalactans 17 and 18 were
deprotected with a saturated solution of ammonia in
MeOH (40 mL) for a week giving the target 19 (95%) and
20 (97%) (Scheme 2).
Acknowledgements
This work was supported by The Chinese Academy of
Sciences (KZCX3-J-08) and by The National Natural

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Y. Zeng et al. / Tetrahedron Letters 44 (2003) 8325–8329
Science Foundation of China (Projects 30070185 and
39970864).
4.10–4.09 (m, 1H, H-5), 4.00–3.97 (dd, 1H, J 4.0 Hz, 10.4
Hz, H-6), 3.73 (s, 3H, CH3O), 1.98 (s, 3H, CH3CO). 12.
1H NMR (400 MHz, CDCl3): l 5.99 (dd, 1H, J 8.0 Hz,
10.4 Hz, H-2), 5.92 (d, 1H, J 3.4 Hz, H-4), 5.88 (d, 1H,
J 3.4 Hz, H-4), 5.84 (d, 1H, J 3.4 Hz, H-4), 5.65 (dd, 1H,
J 8.0 Hz, 10.4 Hz, H-2), 5.60 (dd, 1H, J 3.4 Hz, 10.4 Hz,
H-3), 5.54 (dd, 1H, J 3.4 Hz, 10.4 Hz, H-3), 5.44 (dd, 1H,
J 8.0 Hz, 10.4 Hz, H-2), 5.27 (dd, 1H, J 3.4 Hz, 10.4 Hz,
H-3), 5.22 (d, 1H, J 8.0 Hz, b H-1), 4.69 (d, 1H, J 8.0 Hz,
b H-1), 4.62 (d, 1H, J 8.0 Hz, b H-1), 3.73 (s, 3H, CH3O),
References
1. Pennell, R. I.; Knox, J. P.; Scofield, G. N. J. Cell Biol.
1989, 108, 1967–1973.
2. McNeil, M.; Wallner, S. J.; Hunter, S. W.; Brennan, P. J.
D. Carbohydr Res. 1987, 166, 299–308.
3. Saulnier, L.; Brillouet, J. M.; Moutounet, M. Carbohydr
Res. 1992, 224, 219–235.
4. D’Adamo, P. J. Neuropath Med. 1990, 6, 33–37.
5. Egert, D.; Beuscher, N. Planta Med. 1992, 58, 163–165.
6. Kiyohara, H.; Yamada, H.; Cyong, J. C.; Otsuka, Y. J.
Pharmacobio-Dyn. 1986, 9, 339–346.
1
1.84 (s, 3H, CH3CO). 13. H NMR (400 MHz, CDCl3): l
5.89 (d, 1H, J 3.2 Hz, H-4), 5.86–5.85 (m, 2H, 2H-4), 5.81
(d, 1H, J 3.2 Hz, H-4), 5.75–5.61 (m, 3H, 3H-2), 5.52–
5.49 (m, 2H, 2H-3), 5.38 (dd, 1H, J 3.2 Hz, 10.4 Hz,
H-3), 5.32 (dd, 1H, J 7.8 Hz, 10.4 Hz, H-2), 5.22 (dd, 1H,
J 3.2 Hz, 8.0 Hz, H-3), 5.00 (d, 1H, J 8.0 Hz, b H-1), 4.89
(d, 1H, J 8.0 Hz, b H-1), 4.66 (d, 1H, J 7.8 Hz, b H-1),
4.57 (d, 1H, J 8.0 Hz, b H-1), 3.73 (s, 3H, CH3O), 1.98 (s,
3H, CH3CO), 1.91 (s, 3H, CH3CO). 14. 1H NMR (400
MHz, CDCl3): l 5.90–5.88 (m, 2H, 2H-4), 5.82 (d, 1H, J
3.4 Hz, H-4), 5.81 (dd, 1H, J 8.0 Hz, 10.4 Hz, H-2), 5.71
(dd, 1H, J 8.0 Hz, 10.4 Hz, H-2), 5.64 (dd, 1H, J 3.4 Hz,
10.4 Hz, H-3), 5.57 (dd, 1H, J 3.4 Hz, 10.4 Hz, H-3), 5.27
(dd, 1H, J 3.4 Hz, 10.4 Hz, H-3), 5.17 (d, 1H, J 8.0 Hz,
b H-1), 4.75 (d, 1H, J 8.0 Hz, b H-1), 4.59 (d, 1H, J 8.0
7. Shimizu, N.; Tomoda, M.; Gonda, R. Chem. Pharm.
Bull. (Tokyo) 1989, 37, 1329–1332.
8. Kind, L. S.; Nilsson, B. Immunology 1967, 13, 477–482.
9. (a) Du, Y.; Pan, Q.; Kong, F. Carbohydr. Res. 2000, 323,
28–35; (b) Du, Y.; Pan, Q.; Kong, F. Synlett 1999,
1648–1650.
10. Csa’va’s, M.; Borba’s, A.; Szila’gyi, L.; Lipta’k, A. Syn-
lett 2002, 887–890.
11. Byramova, N. E.; Ovchinnikov, M. V.; Backinowsky, L.
V.; Kochetkov, N. K. Carbohydr. Res. 1983, 124, c8.
12. Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem.
Biochem. 1994, 50, 21–125.
1
Hz, b H-1), 3.73 (s, 3H, CH3O). 15. H NMR (400 MHz,
CDCl3): l 5.91–5.90 (m, 2H, 2H-4), 5.82–5.77 (m, 4H,
2H-4, 1H-2), 5.67 (dd, 1H, J 8.0 Hz, 10.4 Hz, H-2),
5.55–5.51 (m, 2H, 2H-3), 5.38 (dd, 1H, J 3.2 Hz, 10.0 Hz,
H-3), 5.18 (dd, 1H, J 3.6 Hz, 10.0 Hz, H-3), 5.02 (d, 1H,
J 7.8 Hz, b H-1), 4.93 (d, 1H, J 8.0 Hz, b H-1), 4.69 (d,
1H, J 8.0 Hz, b H-1), 4.37 (d, 1H, J 8.0 Hz, b H-1), 3.69
13. All the new compounds involved in the study were iden-
tified by 1H or 13C NMR spectrometry, and elemental
analyses. Selected data for some important compounds:
1
8. H NMR (400 MHz, CDCl3): l 5.91 (d, 1H, J 3.2 Hz,
1
H-4), 5.89 (d, 1H, J 3.2 Hz, H-4), 5.78 (dd, 1H, J 8.0 Hz,
10.4 Hz, H-2), 5.70 (dd, 1H, 5.53 (dd, 1H, J 3.2 Hz, 10.4
Hz, H-3), 5.38 (dd, 1H, J 3.4 Hz, 10.4 Hz, H-3), 5.03 (d,
1H, J 8.0 Hz, b H-1), 4.94 (d, 1H, J 8.0 Hz, b H-1),
4.42–4.39 (dd, 1H, J 5.4 Hz, 11.2 Hz, H-6), 4.27–4.18 (m,
3H, 2H-5, H-6), 4.13–4.10 (dd, 1H, J 4.0 Hz, 10.4 Hz,
H-6), 4.01–3.98 (dd, 1H, J 4.0 Hz, 10.4 Hz, H-6), 3.73 (s,
3H, CH3O), 1.99 (s, 3H, CH3CO). 9. 1H NMR (400
MHz, CDCl3): l 6.99–6.83 (dd, 4H, -C6H4-), 5.89 (d, 1H,
J 3.4 Hz, H-4), 5.82 (d, 1H, J 3.4 Hz, H-4), 5.74 (dd, 1H,
J 8.0 Hz, 10.4 Hz, H-2), 5.70 (dd, 1H, J 8.0 Hz, 10.4 Hz,
H-2), 5.48 (dd, 1H, J 3.4 Hz, 10.4 Hz, H-3), 5.39 (dd, 1H,
J 3.4 Hz, 10.4 Hz, H-3), 5.02 (d, 1H, J 8.0 Hz, b H-1),
4.89 (d, 1H, J 8.0 Hz, b H-1), 4.23–4.21 (m, 1H, H-5),
4.10–4.06 (m, 4H, H-5, 3H-6), 3.99–3.94 (dd, 1H, J 4.4
Hz, 11.2 Hz, H-6), 3.73 (s, 3H, CH3O), 2.00 (s, 3H,
(s, 3H, CH3O). 17. H NMR (400 MHz, CDCl3): l 6.03
(d, 1H, J 3.2 Hz, H-4, Galp), 5.96 (dd, 1H, J 8.0 Hz, 10.4
Hz, H-2, Galp), 5.87 (d, 1H, J 3.6 Hz, H-4, Galp), 5.76
(d, 1H, J 3.6 Hz, H-4, Galp), 5.72 (d, 1H, J 4.8 Hz, H-3,
Araf), 5.68 (s, 1H, H-2, Araf), 5.65 (dd, 1H, J 8.0 Hz,
10.4 Hz, H-2, Galp), 5.61 (d, 1H, J 4.8 Hz, H-3, Araf),
5.53 (s, 1H, H-2, Araf), 5.47 (s, 1H, a H-1), 5.43 (s, 1H,
a H-1), 5.34 (dd, 1H, J 4.0 Hz, 10.4 Hz), 5.26 (d, 1H, J
8.0 Hz, b H-1), 4.82-4.77 (m, 2H), 4.68 (d, 1H, J 7.8 Hz,
b H-1), 4.66–4.62 (m, 2H), 4.55 (d, 1H, J 8.0 Hz, b H-1),
4.39–4.24 (m, 4H), 3.61 (s, 3H, CH3O), 3.40 (dd, 1H, J
3.2 Hz, 10.4 Hz); 13C NMR (100 MHz, CDCl3): l 166.3,
165.9, 165.3, 165.7, 165.6, 165.36, 165.3, 165.1 (PhCO),
156.0, 151.3, 118.8, 114.7 (MeOPh), 106.7, 106.0 (2 a
C-1), 101.7, 101.2, 101.1 (3 b C-1), 82.5, 82.2, 81.3, 78.0,
73.7, 73.3, 72.4, 71.94 71.7, 71.5, 69.9, 68.4, 68.2, 68.0,
67.4, 66.8, 65.6, 63.8, 61.7, 60.5, 55.6 (some signal over-
lapped). Anal. calcd for C133H110O39: C, 68.49; H, 4.75.
Found: C, 68.33; H, 4.66. 18. 1H NMR (400 MHz,
CDCl3): l 5.98 (d, 1H, J 3.2 Hz), 5.85–5.84 (m, 2H),
5.65–5.55 (m, 11H, 2 a-H-1), 5.47–5.37 (m, 8H, 2 a H-1),
4.94 (d, 1H, J 8.0 Hz, b H-1), 4.83–4.49 (m, 8H, b H-1),
4.54–4.45 (m, 3H), 4.41 (d, 1H, J 8.0 Hz, b H-1), 4.32–
4.14 (m, 5H, b H-1), 4.02–3.83 (m, 11H), 3.58 (s, 3H,
CH3O), 3.45–3.40 (m, 2H). 13C NMR (100 MHz, CDCl3):
l 166.3, 165.9, 165.7, 165.3, 165.1, 165.0, 164.9, 164.7
(PhCO), 155.6, 151.5, 118.7, 114.7 (MeOPh), 106.5,
106.2, 106.0, 105.9 (4 a C-1), 101.9, 101.1, 100.9, 100.9
(4b C-1). Anal. calcd for C198H164O59: C, 68.19; H, 4.94.
1
CH3CO), 1.96 (s, 3H, CH3CO). 10. H NMR (400 MHz,
CDCl3): l 8.70 (s, 1H, NH), 6.34 (d, 1H, J 3.2 Hz, a
H-1), 5.87 (d, 1H, J 3.2 Hz, H-4), 5.85 (d, 1H, J 3.2 Hz,
H-4), 5.74 (dd, 1H, J 8.0 Hz, 10.4 Hz, H-2), 5.55 (dd, 1H,
J 3.2 Hz, 10.4 Hz, H-3), 5.41 (dd, 1H, J 3.4 Hz, 10.4 Hz,
H-3), 5.15 (dd, 1H, J 4.0 Hz, 10.4 Hz, H-2), 5.04 (d, 1H,
J 8.0 Hz, b H-1), 4.47–4.44 (dd, 1H, J 5.2 Hz, 11.2 Hz,
H-6), 4.27–4.10 (m, 4H, 2H-5, 2H-6), 4.00–3.97 (dd, 1H,
J 5.2 Hz, 10.4 Hz, H-6), 1.96 (s, 3H, CH3CO). 11. 1H
NMR (400 MHz, CDCl3): l 5.97 (d, 1H, J 3.4 Hz, H-4),
5.84–5.79 (m, 2H, H-4, H-2), 5.74 (dd, 1H, J 8.0 Hz, 10.4
Hz, H-2), 5.44 (dd, 1H, J 3.4 Hz, 10.4 Hz, H-3), 5.40 (dd,
1H, J 3.4 Hz, 10.4 Hz, H-3), 5.04 (d, 1H, J 8.0 Hz, b
H-1), 4.90 (d, 1H, J 8.0 Hz, b H-1), 4.67–4.44 (dd, 1H, J
4.0 Hz, 11.2 Hz, H-6), 4.27–4.10 (m, 3H, H-5, 2H-6),
1
Found: C, 68.30; H, 4.81. 19. H NMR (400 MHz, D2O):
l 5.27 (s, 1H, H-1), 4.99 (s, 1H, H-1), 4.75 (d, 1H, J 8.0

Y. Zeng et al. / Tetrahedron Letters 44 (2003) 8325–8329
8329
1H, J 8.0 Hz, H-1), 4.45 (d, 1H, J 7.9 Hz, H-1), 4.39 (d,
1H, J 7.9 Hz, H-1), 4.38 (d, 1H, J 8.0 Hz, H-1); 13C
NMR (100 MHz, D2O): l 154.3, 150.5, 118.3, 114.9
(MeOPh), 108.5, 108.2, 107.2, 107.1 (4 a C-1), 103.2,
103.1, 102.0, 100.0 (4 b C-1), 55.6. Anal. calcd for
C51H80O38: C, 47.08; H, 6.20. Found: C, 47.23; H, 6.27.
Hz, H-1), 4.54 (d, 1H, J 7.9 Hz, H-1), 4.39 (d, 1H, J 7.9
Hz, H-1); 13C NMR (100 MHz, D2O): l 108.1, 107.0 (2
a C-1), 103.1, 103.1, 101.4 (3b C-1). Anal. calcd for
C35H54O25: C, 48.05; H, 6.22. Found: C, 48.19; H, 6.17.
20. H NMR (400 MHz, D2O): l 5.34 (s, 1H, H-1), 5.29
(s, 1H, H-1), 5.05 (s, 1H, H-1), 5.01 (s, 1H, H-1), 4.54 (d,
1