Regio- and stereoselective synthesis of 1→5-linked α-L- arabinofuranosyl oligosaccharides

Article abstract of DOI:10.1055/s-1999-3170

Regio- and stereoselective synthesis of furanosyl oligosaccharides in moderate to very good yields using arabinofuranosyl trichloroacetimidates as glycosyl donors and unprotected or partially protected glycosides as acceptors was described. A convergent synthesis of 1→5-linked α-L- arabinofuranosyl octamer was presented.

Full text of DOI:10.1055/s-1999-3170

1648
LETTER
Regio- and Stereoselective Synthesis of 1Æ5-Linked a-L-Arabinofuranosyl
Oligosaccharides
Yuguo Du, Qingfeng Pan, Fanzuo Kong*
Research Center for Eco-Environmental Sciences, Academia Sinica, P. O. Box 2871, Beijing 100085, P. R.China
Fax 86-10-62923563; E-mail: fzkong@mail.rcees.ac.cn
Received 15 July 1999
Dedicated to Prof. Pierre Sinaÿ on the occasion of his 62nd birthday.
achieved recently.2 However, there has been no break-
Abstract: Regio- and stereoselective synthesis of furanosyl oli-
through so far in the regio- and stereoselective synthesis
gosaccharides in moderate to very good yields using arabinofurano-
of oligofuranose due to the difficulty in the preparation of
syl trichloroacetimidates as glycosyl donors and unprotected or
stable furanosyl donors3 and lack of efficient protecting
partially protected glycosides as acceptors was described. A conver-
gent synthesis of 1Æ5-linked a-L-arabinofuranosyl octamer was strategies in differentiation of hydroxy groups in furano-
syl system.4 The glycosyl imidate donors, initially pro-
presented.
posed by Sinaÿ5 and developed few years later by
Key words: imidate, regio- and stereoselective synthesis, furanosyl
oligosaccharide, arabinose
Schmidt,6 is so far one of the most powerful alternatives
in oligosaccharide synthesis. However, to the best of our
knowledge, few examples of furanosyl trichloroacetimi-
dates have been reported7 and the regioselective glycosy-
The biological significance of glycocojugates has stimu-
lation of oligofuranoses was inconceivably neglected.
Herein, we present the use of perbenzoylated arabinofura-
nosyl trichloroacetimidates as the donors for regio- and
stereoselective glycosylation with unprotected or partially
protected carbohydrate acceptors. The efficiency of this
method was further proved by arabinofuranosyl oligosac-
charide syntheses.
lated much synthetic activity in glycoside synthesis in the
past years.1 The specific structural constraints in glycosid-
ic bond-formation often lead to laborious synthetic trans-
formation, complex protecting group manipulations, and
tedious intermediate isolations, which complicate the
overall synthetic process and decrease synthetic efficien-
cy.
Our initial interest was in the preparation of arabinogalac-
tan moiety 3. We found that coupling of perbenzoylated
arabinofuranosyl trichloroacetimidate 1 with galactose
residue 2 gave exclusively regioselective product 3, while
To facilitate the synthesis of oligosaccharides, regiospe-
cific glycosylation of glycosyl donors with unprotected or
partially protected sugar acceptors has been taken tremen-
dous efforts. Some of the exciting results have been
a. TMSOTf , CH2Cl2. b. TMSOTf, CH3CN.
Scheme 1
Synlett 1999, No. 10, 1648–1650 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Regio- and Stereoselective Synthesis of 1Æ5-Linked a-L-Arabinofuranosyl Oligosaccharides
1649
Convergent synthesis of 1Æ5-linked a-L-arabinofuranosyl oligosaccharides- a. TMSOTf, CH2Cl2, - 42 oC. b. BzCl, Pyr. c. PdCl2, NaOAc, HO-
Ac; then Cl3CCN, K2CO3, CH2Cl2. d. BnOC(NH)CCl3, TMSOTf. e. NaOMe, MeOH. f. Pd(OH)2/C, H2, EtOAc; then Ac2O, Pyr. g. Pd(OH)2/
C, H2, EtOAc; then BzCl, Pyr.
Scheme 2
the use of peracetylated arabinofuranosyl bromide as the ence to compound 11. Although we have no convincing
donor gave a mixture of two regioisomers with excessive evidence to rationalise the reaction, we thought the inter-
1Æ3-linked product. This result stimulated us to investi- mediate might be a sugar-sugar ortherester which rear-
gate the regioselective coupling of donor 1 with a variety ranged in situ to give 1,2-trans linked product.9
of partially protected acceptors. Thus, 1 was condensed
Encourage by the results described above, we turned our
attention on the facile synthesis of a-(1Æ5)-linked L-ara-
with diol 4 in anhydrous CH2Cl2 in the presence of TM-
o
1
SOTf at – 42 C giving difuranoside 5 in 85% yield. H
NMR of acetylated 5 (J1’,2’ <1 Hz and the chemical shift
of H-3 was moved downfield to 5.29 ppm after acetyla-
tion) promised a-1Æ5 linkage in 5. The same coupling re-
action was applied to 1 and triol 6 to furnish 7 in 79%
yield. The stereo- and regioselectivity in this process was
assured by 1H-13C COSY of 7, i.e. the characteristic cou-
pling constant of J1’,2’ (J1’,2’ < 1 Hz in this case) indicated
a stereoselectivity while C-5 (63.5 ppm in 13C NMR) and
downfield H-2, H-3 (5.09, 5.20 ppm, respectively) in its
acetylated derivative confirmed 1Æ5 linkage of 7.8 When
donor 1 was coupled with D-glucofuranose triol 12 in
CH2Cl2, a sharply decreased yield was obtained (about
20%) due to the poor solubility of 12 in CH2Cl2. The same
reaction proceeded in anhydrous CH3CN gave 53% (cor-
rected yield based on 28% recovered acceptor 12) 1Æ6-
linked difuranose 13, together with ~10% by-product.
When D-galactopyranose triol 8 and D-mannopyranose
diol 10 were glycosylated with 1 in CH2Cl2, a very low re-
gioselectivity was found in the formation of 9 while a
moderate regioselectivity (3.4:1) was obtained in prefer-
binofuranosyl oligosaccharides which are fragments in ar-
abinogalactan and some of the Chinese Medicines.10
Direct glycosylation of 1 with unprotected allyl a-L-ara-
binofuranoside 14 under the promotion of TMSOTf at –42
oC provided 15 regioselectively in 78% yield. Compound
15 was fully benzoylated with BzCl in pyridine, followed
by deallylation (PdCl2, NaOAc, HOAc) and activation
(Cl3CCN, K2CO3, CH2Cl2) to give difuranosyl donor 17 in
70% yield. Glycosylation of 17 with unprotected 14 as de-
scribed above furnished homo-trisaccharide 18 easily
(81%). In another route, 15 was benzylated using benzyl
trichloroacetimidate and TMSOTf 11 to give difuranoside
19 which was subjected to Zemplén deacylation furnish-
ing triol 20 (70% from 15). Reaction of disaccharide do-
nor 17 with triol 20 under the same glycosylation
conditions generated homo-tetrasaccharide 21 in 79%
yield. 21 was subjected to hydrogenolysis (Pd(OH)2/C,
H2), followed by acetylation (Æ 24), deallylation (PdCl2,
NaOAc, HOAc) and activation (Cl3CCN, K2CO3) ob-
tained tetrasaccharide trichloroacetimidate 25 (65% from
Synlett 1999, No. 10, 1648–1650 ISSN 0936-5214 © Thieme Stuttgart · New York

1650
Y. Du et al.
LETTER
(4) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, John Wiley & Sons, Inc.; New York, 1991.
(5) Pougny, J. R.; Jacquinet, J. C.; Nassr, M.; Duchet, D.; Milat,
M.-L.; Sinaÿ, P. J. Am. Chem. Soc. 1977, 99, 6762.
(6) Schmidt, R. R.; Michel, J. Angew. Chem. Int. Ed. 1980, 19,
731.
(7) Gelin, M.; Ferrieres, V.; Plusquellec, D. Carbohydr. Lett.
1997, 2, 381. Schmidt, R. R.; Hoffmann, M. Tetrahedron Lett.
1982, 23, 409. Chiu-Machado, I.; Castro-Palomio, J. C.;
Madrazo-Alonso, O.; Lopetegui-Palacios, C.; Verez-
Bebcomo, V. J. Carbohydr. Chem. 1995, 14, 551.
21). Convergently, 21 was benzylated under mild acid
condition (Æ 22) and then deacylated to give tetrasaccha-
ride acceptor 23 (67% from 21). 4 + 4 coupling reaction
was carried out between 23 and 25 as described for the
preparation of 15, followed by debenzylation (H2,
Pd(OH)2/C), benzoylation (Æ 27) and Zemplén deacyla-
tion to finish a-(1Æ5)-linked L-arabinofuranosyl octamer
28 (71% based on 23).
In summary, we have shown here a very effective method
for regio- and stereoselective synthesis of 1Æ5-linked a-
L-arabinofuranosyl oligosaccharide using benzoylated ar-
abinofuranosyl trichloroacetimidates as the glycosyl do-
nors. The present work may thus open an unexplored
route to other furanosyl oligosaccharides with much sim-
plified procedures. Further investigation of the applica-
tion of this new finding to build bioactive furanosyl
oligosaccharides is in process and the biological, chemical
and physical properties of the synthesized furanosyl oli-
gomers will be published in due course.
(8) Typical procedure: Furanosyl trichloroacetimidate (500 mg
scale) and 0.95 equiv. of unprotected acceptor were dried
together under high vacuum for 2 h, then dissolved in
anhydrous CH2Cl2 (15 mL). TMSOTf (0.15 equiv.) in
anhydrous CH2Cl2 (35 mL) was added dropwise at –42 oC
with N2 protection. The reaction mixture was stirred at –42 oC
for 40 to 90 min, then neutralized with triethylamine,
concentrated under reduced pressure, and purified on silica gel
column with EtOAc–petroleum ether. All new compounds
gave satisfactory elemental analysis results. Selected 13
C
NMR (100 MHz, CDCl3) are as follows: 7 54.9 (C-5’), 63.5
(C-5), 77.5 (C-3), 78.1 (C-2), 79.5 (C-4), 81.8 (C-3’), 82.0 (C-
2’), 85.4 (C-4’), 106.1 (C-1), 109.2 (C-1’). 24 20.5, 20.6, 20.7,
20.9 (CH3CO), 63.5, 65.0, 65.5, 65.9 (C-5I-IV), 67.7 (C=C-C-
), 104.4, 105.1, 105.7, 105.8 (C-1I-IV), 76.4, 76.8, 77.2, 77.7,
80.9, 81.1, 81.3, 81.4, 81.6, 81.8, 81.9, 82.0 (C-2-4I-IV), 117.4
(C=C-C-), 128.2-129.8 (CAr), 132.9 (C=C-C-), 133.2, 133.3,
133.4, 133.5, 133.6 (CAr), 165.0, 165.1, 165.5, 165.6, 166.1 (5
PhCO), 169.6, 169.8, 170.0, 170.1 (4 CH3CO). 27 104.8,
105.3, 105.4, 105.7, 105.8, 105.9, 106.2, 106.6 (C-1I-VIII).
MALDI-TOF MS Calcd for C142H130O50: 2634.7 [M]. Found:
2658.2 [M+Na]. 28 (D2O): 66.0-66.5 (C-5), 68.1 (C=C-C-),
75.7-76.4 (C-3), 80.3-80.6 (C-4), 81.9-82.0 (C-2), 107.0-
107.2 (C-1), 108.3 (C-1 on reducing end), 118.1 (C=C-C-),
133.1 (C=C-C-). ESMS Calcd for C43H70O33: 1114.38 [M].
Found: 1115.3 [M+H].
Acknowledgement
This work was supported by The Chinese Academy of Sciences
(Project KJ952J1510) and The National Natural Science Foundation
of China (Projects 29672049 and 29802009).
References and Notes:
(1) Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503. Zhang,
Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong,
C.-H.; J. Am. Chem. Soc. 1999, 121, 734. Danishefsky, S. J.;
Bilodeau, M. T. Angew. Chem. Int. Ed. Engl. 1996, 35, 1380.
(2) Wang, W.; Kong, F. J. Org. Chem. 1998, 63, 5744. Wang, W.;
Kong, F., Angew. Chem. Int. Ed. 1999, 38, 1247. Oshima, K.;
Aoyama, Y. J. Am. Chem. Soc. 1999, 121, 2315. Hanessian, S.
In Preparative Carbohydrate Chemistry; Hanessian, S. Ed.;
Marcel Dekker Inc.; New York, 1997, p381. Unverzagt, C.
Angew. Chem. Int. Ed. Engl. 1994, 33, 1102. Verduyn, R.;
Douwes, M.; van der Klein, P.A.M.; Moesinger, E.M.; van der
Marel, G.A.; van Boom, J.H. Tetrahedron 1993, 49, 7301.
Han, X.-B.; Jiang, Z.-H.; Schmidt, R.R. Liebigs Ann. Chem.
1993, 853.
(9) Nukada, T.; Berces, A.; Zgiershi, M. Z.; Whitefield, D. M. J.
Am. Chem. Soc. 1998, 120, 13291. Han, X.-B.; Jiang, Z.-H.;
Schmidt, R. R. Liebigs. Ann. Chem. 1993, 853.
(10) Yamada, H. Carbohydr. Polymers 1994, 25, 269.
(11) Wellel, H.-P.; Lversen, T.; Bundle, D. R. J. Chem. Soc. Perkin
Trans. I 1985, 2247.
Article Identifier:
1437-2096,E;1999,0,10,1648,1650,ftx,en;Y15799ST.pdf
(3) Velty, R.; Benvegnu, T.; Gelin, M.; Privat, E.; Plusquellec, D.
Carbohydr. Res. 1997, 299, 7. D’Souza, F. W.; Cheshev, P.
E.; Ayers, J. D.; Lowary, T. L. J. Org. Chem. 1998, 63, 9037.
Synlett 1999, No. 10, 1648–1650 ISSN 0936-5214 © Thieme Stuttgart · New York