Synthesis of tetrameric arabinogalactans based on 1,2-anhydrosugars

Article abstract of DOI:10.1002/(sici)1099-0690(199801)1998:1<91::aid-ejoc91>3.0.co;2-n

The spacer-containing tetrameric arabinogalactans 1-3, suitable for CCRC-M7 epitope characterization, are readily accessible by ZnCl₂-assisted stepwise elongation of 11-methoxycarbonylundecanol 9 with the 1,2-anhydrogalactose building unit 6. NIS/cat. TfOH-mediated glycosylation of the newly formed 2-OH, 2′-OH, or 2″-OH function in the β-(1→6)-galactoside backbone with the 1-thioarabinofuranoside donor 8, followed by deprotection, provided the target tetramers in high overall yield.

Full text of DOI:10.1002/(sici)1099-0690(199801)1998:1<91::aid-ejoc91>3.0.co;2-n

FULL PAPER
Synthesis of Tetrameric Arabinogalactans Based on 1,2-Anhydrosugars
Cornelis M. Timmers, Suzanne C.M. Wigchert, Michiel A. Leeuwenburgh, Gijsbert A. van der Marel,
and Jacques H. van Boom*
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University,
P.O. Box 9502, NL-2300 RA Leiden, The Netherlands
Fax: (internat.) ϩ31(0)71-5274307
E-mail: marel g@rulgca.leidenuniv.nl
᎐
Received July 24, 1997
Keywords: Carbohydrates / Glycals / Arabinogalactans /1,2-Anhydrosugars / Monoclonal antibodies / CCRC-M7 /
Thioethyl furanosides
The spacer-containing tetrameric arabinogalactans 1؊3,
suitable for CCRC-M7 epitope characterization, are readily
newly formed 2-OH, 2Ј-OH, or 2ЈЈ-OH function in the β-
(1Ǟ6)-galactoside backbone with the 1-thioarabinofurano-
accessible by ZnCl2-assisted stepwise elongation of 11-meth- side donor 8, followed by deprotection, provided the target
oxycarbonylundecanol
9
with the 1,2-anhydrogalactose
tetramers in high overall yield.
building unit 6. NIS/cat. TfOH-mediated glycosylation of the
Introduction
Scheme 1
The study of complex carbohydrates present at plant cell-
surfaces using monoclonal antibodies is an expanding field
of phytobiology.[1] Antibodies generated against specific
plant cell-wall carbohydrates may serve as probes in iden-
tifying cognate structural elements in outer membrane sac-
charides of other plant species. The usefulness of this con-
cept relies upon characterization of the epitopes recognized
by the antibodies.
Albersheim et al. recently reported[2] the elicitation of
several monoclonal antibodies directed against pectic poly-
saccharide rhamnogalacturonan I (RG-I), isolated from
suspension-cultured sycamore maple (Acer pseudoplatanus).
A representative example of this class of antibodies is
CCRC-M7, which recognizes an epitope widely distributed
among plant complex carbohydrates, such as RG-I, several
arabinogalactans and membrane glycoproteins. It was es-
tablished[3] that this immunogenic region consists of a β-
(1Ǟ6)-linked galactan containing at least three -galacto-
pyranosyl residues functionalized at one hydroxyl function
with an α-linked -arabinofuranosyl unit. In order to study
the minimal epitope perceived by CCRC-M7 in more detail,
the availability of tetrameric arabinogalactans in which a -
arabinosyl moiety is attached to a predefined position in a
trimeric β-(1Ǟ6)-linked galactan backbone is highly desir-
able. We here report the assembly of the tetrameric arabino-
galactosides 1؊3 (see Scheme 1) suitable for further CCRC-
M7 epitope characterization.
is functionalized with a dodecanoate spacer to enable con-
jugation to a solid support via a peptide linkage. It occurred
to us that the arabinogalactosides 1؊3 are accessible by oxi-
dative coupling of galactals.[4][5] This methodology com-
prises stereoselective epoxidation of a suitably protected ga-
lactal with 3,3-dimethyldioxirane (DMD)[6] followed by
ZnCl2-catalyzed condensation of the resulting 1,2-anhydro-
sugar with a galactal acceptor to give a dimeric galactal.
The oligosaccharide chain may then be iteratively elongated
from the non-reducing end using an excess of glycal ac-
ceptor. A propitious feature of the glycal approach is the
formation of an unprotected 2-hydroxyl function, which is
amenable to direct arabinosylation. Earlier studies from our
laboratory revealed[7] that ethyl 1-thiofuranosides are useful
starting compounds for the introduction of furanoside resi-
dues in oligosaccharides. However, the presence of a glycal
function in the growing β-(1Ǟ6)-linked galactoside back-
bone excludes iodonium ion-mediated arabinosylation of
Results and Discussion
In the target tetramers 1؊3 the -arabinosyl residue is the 2-OH group with a thioethyl donor. Iodonation of the
either α-anchored to position O-2 (i.e. 3), O-2Ј (i.e. 2) or enol ether moiety could be circumvented by stepwise exten-
O-2ЈЈ (i.e. 1) of the β-(1Ǟ6)-linked galactosyl framework. sion of the galactoside framework from the reducing end
Furthermore, the reducing end of the arabinogalactosides (i.e. the spacer moiety) via condensation of the acceptor
Eur. J. Org. Chem. 1998, 91Ϫ97
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1434Ϫ193X/98/0101Ϫ0091 $ 17.50ϩ.50/0
91

J. H. van Boom et al.
FULL PAPER
function in the growing chain with an excess of monomeric epoxidation of fully protected galactal 5, with methoxycar-
1,2-anhydrogalactose donor.
bonylundecanol 9 gave exclusively the β-linked spacer-con-
taining galactoside 10 (see Scheme 3) in 78% yield. Glyco-
sylation of the 2-OH in 10 with ethyl 1-thio-arabinofurano-
Scheme 2. Reagents and conditions: (i) NaH, BnBr, Ph3PMeI,
THF, 30 °C, 3 h, 82%; (ii) 3,3-dimethyldioxirane,
CH2Cl2/acetone, 0 °C, 1 min, quant.; (iii) EtSH, SnCl4, side donor 8, obtained by SnCl4-mediated thioethylation of
previously described[10] arabinofuranosyl acetate 7, under
toluene, 0 °C, 1 h, 72%.
the agency of N-iodosuccinimide (NIS) and catalytic triflic
acid (TfOH),[11] proceeded stereoselectively to afford the α-
linked dimer 13 in a yield of 91%. Tetra-n-butylammonium
fluoride (TBAF)-mediated desilylation of 13 and stereose-
lective condensation of the primary hydroxyl in 14 with the
1,2-anhydrogalactose 6 led to the isolation of trimer 20.
Repetition of the latter sequence of reactions, i.e. desilyl-
ation of 20, followed by regioselective coupling of the pri-
mary hydroxyl in 21 with donor 6, furnished the tetrameric
fragment 25. Removal of the silyl protective group in 25
´
with TBAF, Zemplen debenzoylation, and then hydro-
genolysis gave the target tetrasaccharide 3 (64% overall
yield), the spectral data of which were in full accord with
the proposed structure.
Based on the above described considerations, the syn-
Isomer 2, bearing one arabinosyl residue at position O-
thesis of target molecules 1؊3, starting from the 1,2-anhy- 2Ј of the trimeric galactosyl backbone, was constructed in
drogalactose derivative 6 (see Scheme 2), thioethyl -arabin- a similar fashion starting from galactoside 10. In order to
ofuranosyl donor 8 and spacer alcohol 9,[8] was undertaken. prevent undesired arabinosylation, the free 2-hydroxyl in 10
Zinc chloride-assisted condensation of donor 6, prepared was benzoylated. Desilylation of the fully protected galacto-
by benzylation of known[9] 6-O-tert-butyldiphenylsilyl side 11 gave the partially protected monomeric building
(TBDPS)--galactal 4 and subsequent DMD-mediated unit 12. ZnCl2-catalyzed elongation of 12 with 1,2-anhydro-
Scheme 3. Reagents and conditions: (i) ZnCl2, THF, 0 °C, 10 min, 10: 78%, 15: 71%, 20: 68%, 22: 67%, 24: 63%, 25: 60%; (ii) BzCl, pyr,
2Ϫ3 h, 11: 91%, 16: 90%; (iii) TBAF, THF, 3Ϫ5 h, 12: 82%, 14: 80%, 17: 76%, 19: 81%, 21: 76%; (iv) NIS, cat. TfOH,
ClCH2CH2Cl/THF (3:1, v/v), 0 °C, 1 h, 13: 91%, 18: 69%, 23: 82%; (v) a. TBAF, THF, 3Ϫ5 h; b. KOtBu, CH2Cl2/MeOH
(1:2, v/v), 30 min; c. H2 (3 atm.), Pd/C, tBuOH/H2O (3:1, v/v), 12 h, 1: 66%, 2: 70%, 3: 64%
92
Eur. J. Org. Chem. 1998, 91Ϫ97

Tetrameric Arabinogalactans
FULL PAPER
TLC-analysis was carried out on DC-Fertigfolien (Schleicher &
Schüll F1500, LS254) with detection by UV-absorption (254 nm)
where applicable and charring with 20% H2SO4 in MeOH or am-
monium molybdate (25 g/l) and ceric ammonium sulfate (10 g/l) in
10% aq. H2SO4. Ϫ Reactions were run at ambient temperature,
unless otherwise stated. Traces of water in the glycosides were re-
moved by coevaporation with acetonitrile, 1,2-dichloroethane, pyri-
dine or toluene.
galactose 6 led to the exclusive formation of the β-linked
dimer 15, the 2Ј-hydroxyl of which was arabinosylated with
donor 8 under the agency of NIS/cat. TfOH, affording the
fully protected trimer 18 in 49% overall yield from 12. Desi-
lylation of 18 and introduction of the terminal galactosyl
residue by ZnCl2-assisted condensation of trimer 19 with
1,2-oxirane 6 led to the tetrasaccharide 24, deprotection of
which gave homogeneous arabinogalactoside 2 (70% yield).
The assembly of target tetrasaccharide 1 commences with
the benzoylation of dimer 15 to give the fully protected di-
galactoside 16. Removal of the TBDPS-group in 16 fol-
lowed by stereoselective ZnCl2-assisted condensation of di-
saccharide 17 with 1,2-anhydrogalactose 6 furnished trimer
22 in 51% overall yield. Finally, arabinosylation of the 2ЈЈ-
hydroxyl in 22 by coupling with thioethyl donor 8 provided
1,5-Anhydro-2-deoxy-3,4-di-O-benzyl-6-O-tert-butyldiphenylsilyl-
-lyxo-hex-1-enitol (5): A solution of 6-O-tert-butyldiphenylsilyl--
galactal[9] (4, 3.84 g, 10.0 mmol) in THF (30 ml) was heated to 30
°C. To this solution, NaH (60% dispersion in mineral oil, 2.4 g, 60
mmol) was added and the mixture was stirred for 10 min. Sub-
sequently, methyltriphenylphosphonium iodide (8.1 g, 20 mmol)
and benzyl bromide (7.2 ml, 60 mmol) were added and the reaction
mixture was stirred at 30 °C for 3 h. Methanol (3 ml) was added
the fully protected tetrameric fragment 23, which was and the heterogeneous mixture was concentrated in vacuo. The resi-
due was dissolved in diethyl ether (200 ml), washed with sat. aq.
NaCl (3 ϫ 50 ml), dried (MgSO4) and concentrated under reduced
pressure. Purification of the residue was effected by silica gel chro-
matography (0Ϫ10% EtOAc/light petroleum) to give fully protected
further processed to give the deprotected galactoside 1 (66%
yield). The biological activity of tetramers 1؊3 is presently
under investigation.[12]
1
galactal 5 (4.62 g, 8.2 mmol, 82%) as a colorless oil. Ϫ H NMR
Conclusion
(CDCl3): δ ϭ 7.65Ϫ7.23 (m, 20 H, Harom), 6.25 (dd, 1 H, H1, J1,2 ϭ
6.2 Hz, J1,3 ϭ 1.0 Hz), 4.80 (dd, 1 H, H2, J2,3 ϭ 0.9 Hz), 4.82 (AB,
2 H, CH2 Bn), 4.60 (AB, 2 H, CH2 Bn), 4.10 (ddd, 1 H, H3, J3,4 ϭ
4.0 Hz), 3.91 (dd, 1 H, H4, J4,5 ϭ 3.4 Hz), 3.89Ϫ3.78 (m, 3 H, H5/
H6/H6Ј), 1.03 (s, 9 H, CH3 tBu). Ϫ 13C{1H} NMR (CDCl3): δ ϭ
144.3 (C1), 138.8, 138.5 (Cq Bn), 135.8Ϫ127.5 (Carom), 133.7, 133.3
(Cq TBDPS), 100.0 (C2), 77.5, 71.7, 71.2 (C3/C4/C5), 73.6, 71.0
(CH2 Bn), 62.3 (C6), 27.0 (CH3 tBu), 19.5 (Cq tBu).
The stereoselective assembly of arabinogalactosides 1؊3
illustrates that (1Ǟ2)-branched oligosaccharides are readily
accessible via stepwise elongation of the sugar chain from
the reducing end with 1,2-anhydroglycoside building blocks
(e.g. 6). Moreover, the absence of a glycal function in the
growing chain permits iodonium ion-mediated glycosy-
lation of the free 2-OH function with thioethyl donors (e.g.
8). Extension of this so-called “reversed glycal approach”
to a solid support is currently under investigation.
1,2-Anhydro-3,4-di-O-benzyl-6-O-tert-butyldiphenylsilyl-Ͱ--ga-
lactopyranose (6): To a stirred and cooled (0 °C) solution of galac-
tal 5 (2.82 g, 5.0 mmol) in CH2Cl2 (10 ml) a freshly prepared solu-
tion of 3,3-dimethyldioxirane (DMD, 67 ml, 0.09 , 6.0 mmol) in
acetone was added dropwise. Immediately after the last addition,
the reaction mixture was concentrated under reduced pressure to
afford epoxide 6 as a white solid in quantitative yield (2.90 g, 5.0
mmol). Ϫ 1H NMR (CDCl3): δ ϭ 7.71Ϫ7.25 (m, 20 H, Harom),
4.90 (d, 1 H, H1, J1,2 ϭ 3.8 Hz), 4.76 (AB, 2 H, CH2 Bn), 4.58
(AB, 2 H, CH2 Bn), 3.92 (dd, 1 H, H3, J2,3 ϭ 1.4 Hz, J3,4 ϭ 3.0
Hz), 3.71 (dd, 1 H, H4, J4,5 ϭ 4.3 Hz), 3.67 (m, 1 H, H5), 3.64 (dd,
The work described in this paper was supported by the Nether-
lands Foundation for Chemical Research (SON) with financial aid
from the Netherlands Organization for Scientific Research (NWO).
Experimental Section
1
General: H-NMR and 13C-NMR spectra were recorded with a
Jeol JNM-FX-200 (200/50.1 MHz), a Bruker WM-300 (300/75.1
MHz), or a Bruker DMX-600 spectrometer (600/150.3 MHz).
Chemical shifts are given in ppm (δ) relative to tetramethylsilane
as internal standard. Ϫ Mass spectra were recorded on a Finnigan
MAT TSQ70 triple quadrupole mass spectrometer. Ϫ Optical ro-
tations were determined using a Propol automatic polarimeter. Ϫ
Dichloromethane, pyridine and toluene were boiled under reflux
1 H, H6, J5,6 ϭ 3.5 Hz, J6,6Ј ϭ 10.8 Hz), 3.52 (dd, 1 H, H6Ј, J5,6Ј
ϭ
1.9 Hz), 3.12 (dd, 1 H, H2), 1.04 (s, 9 H, CH3 tBu). Ϫ 13C{1H}
NMR (CDCl3): δ ϭ 138.2, 137.4 (Cq Bn), 135.0Ϫ127.0 (Carom),
132.7, 132.6 (Cq TBDPS), 76.6 (C1), 76.2, 71.7, 69.1 (C3/C4/C5),
74.3, 71.0 (CH2 Bn), 61.7 (C6), 51.2 (C2), 26.4 (CH3 tBu), 18.7
(Cq tBu).
˚
with CaH2 for 3 h, distilled, and stored over molecular sieves (4 A).
Triethylamine was distilled from CaH2. Acetone (Boom Chemicals,
c.p.), 1,2-dichloroethane (Biosolve, HPLC-grade), N,N-dimethyl-
Ethyl 2,3,5-Tri-O-benzoyl-1-thio-Ͱ--arabinofuranoside (8): To a
cooled (0 °C) and stirred solution of arabinofuranosyl acetate 7[11]
formamide (DMF, Baker, p.a.), dimethyl sulfoxide (DMSO, Baker, (5.04 g, 10 mmol) and ethanethiol (0.81 ml, 11 mmol) in toluene
p.a.), 1,4-dioxane (Baker, p.a.), and tetrahydrofuran (THF, Bio-
solve, HPLC-grade) were stored over molecular sieves (4 A). Meth-
(20 ml), tin tetrachloride (SnCl4, 0.12 ml, 1.0 mmol) was added
dropwise. The reaction mixture was stirred for 1 h after which tri-
˚
anol (Biosolve, HPLC-grade) was stored over molecular sieves (3 ethylamine (1 ml) and diethyl ether (250 ml) were sequentially ad-
˚
A). Zinc chloride (ZnCl2, Merck, p.a.) was dissolved in THF (1.0 
ded. The resulting solution was washed with aq. KF (1.0 , 2 ϫ
50 ml) and aq. NaHCO3 (1.0 , 2 ϫ 50 ml), dried (MgSO4), and
˚
solution) and stored over molecular sieves (3 A). Benzoyl chloride
(Merck), benzyl bromide (Merck), tert-butyldiphenylsilyl chloride concentrated in vacuo. Purification of the residue was effected by
(TBDPSCl, Acros), ethanethiol (Fluka), N-iodosuccinimide (NIS, silica gel chromatography (10Ϫ30% EtOAc/light petroleum) to give
Aldrich), methyltriphenylphosphonium iodide (Aldrich), oxone
(Aldrich), and trifluoromethanesulfonic acid (TfOH, Fluka) were
used as received. Ϫ Column chromatography was performed on
Merck Kieselgel 60 (230Ϫ400 mesh). Ϫ Gel permeation chroma-
tography was accomplished on Sephadex LH-20 (Pharmacia). Ϫ
8 as an oil, which was crystallized from EtOH (50 ml), resulting in
the isolation of 8 as colorless needles (3.64 g, 7.2 mmol, 72%). Ϫ
mp. 70Ϫ72 °C. Ϫ [α]D ϭ Ϫ34.4 (c ϭ 1, CHCl3). Ϫ 1H NMR
(CDCl3): δ ϭ 8.12Ϫ7.25 (m, 15 H, Harom), 5.64 (dd, 1 H, H3, J2,3 ϭ
3.6 Hz, J3,4 ϭ 1.9 Hz), 5.60 (d, 1 H, H1, J1,2 ϭ 1.9 Hz), 5.56 (dd,
Eur. J. Org. Chem. 1998, 91Ϫ97
93

J. H. van Boom et al.
1 H, H2), 4.86 (dd, 1 H, H5, J4,5 ϭ 3.1 Hz, J5,5Ј ϭ 10.2 Hz), 62.2 (C6), 50.9 (OMe), 33.7 (CH2CϭO spacer), 29.0, 29.0, 28.9,
FULL PAPER
4.77Ϫ4.71 (m, 2 H, H4/H5Ј), 2.77 (q, 2 H, CH2 Et), 1.36 (t, 3 H,
28.8, 28.7, 28.6, 28.5, 25.4, 24.6 (CH2 spacer), 26.5 (CH3 tBu), 18.8
CH3 Et). Ϫ 13C{1H} NMR (CDCl3): δ ϭ 165.6, 165.1, 164.9 (Cϭ (Cq tBu).
O Bz), 133.1Ϫ127.9 (Carom), 128.5 (Cq Bz), 87.7 (C1), 82.6, 80.3,
General Procedure for 6-O-Desilylation: Tetra-n-butylammonium
77.8 (C2/C3/C4), 63.0 (C5), 24.8 (CH2 Et), 14.5 (CH3 Et). Ϫ
C28H26O7S (506.1): calcd. C 66.39; H 5.17; found: C 66.28; H 5.22.
fluoride (1.0  solution in THF, 1.5 ml, 1.5 mmol) was added to a
stirred solution of the appropriate 6-O-TBDPS ether (1.0 mmol)
in THF (5 ml). When TLC-analysis (50% EtOAc/light petroleum)
showed complete disappearance of the starting compound (3Ϫ5 h)
General Procedure for the Introduction of β-(1Ǟ6)-Galactosidic
Linkages: To a stirred and cooled (0 °C) solution of the appropriate
glycosyl acceptor (1.0 mmol) and 1,2-anhydrogalactose 6 (0.87 g, the reaction mixture was diluted with EtOAc (100 ml) and washed
1.5 mmol) in THF (5 ml) was added dropwise, under a continuous with sat. aq. NaCl (3 ϫ 25 ml). The organic phase was dried
stream of dry nitrogen, a solution of ZnCl2 in THF (1.0 , 2.5 ml, (MgSO4), and concentrated in vacuo, after which the residue was
2.5 mmol). The reaction mixture was stirred for 10 min, after which
the solution was diluted with EtOAc (100 ml), washed with sat. aq.
NaCl (3 ϫ 25 ml) and aq. NaHCO3 (1.0 , 25 ml), dried (MgSO4),
and concentrated in vacuo. Purification of the residue was ac-
complished by silica gel chromatography (0Ϫ50% EtOAc/light
petroleum) and Sephadex LH-20 gel filtration (eluent: CH2Cl2/
MeOH, 2:1, v/v) to give the respective oligomer as a white solid.
purified by silica gel chromatography (20Ϫ50% EtOAc/light petro-
leum) to furnish the corresponding primary alcohol as a white
solid.
11-Methoxycarbonylundecanyl 2-O-Benzoyl-3,4-di-O-benzyl-β--
galactopyranoside (12): Yield: 0.787 g, 1.16 mmol, 82% based on
1
1.30 g, 1.42 mmol of 11. Ϫ H NMR (CDCl3): δ ϭ 8.05Ϫ7.19 (m,
15 H, Harom), 5.65 (dd, 1 H, H2, J1,2 ϭ 8.1 Hz, J2,3 ϭ 8.7 Hz), 4.87
11-Methoxycarbonylundecanyl 3,4-Di-O-benzyl-6-O-tert-butyldi-
(AB, 2 H, CH2 Bn), 4.77 (AB, 2 H, CH2 Bn), 4.32 (d, 1 H, H1),
phenylsilyl-β--galactopyranoside (10): Yield: 1.90 g, 2.34 mmol, 3.90 (d, 1 H, H4, J3,4 ϭ 2.6 Hz), 3.82 (dd, 1 H, H3), 3.72Ϫ3.68 (m,
1
78% based on 0.690 g, 3.00 mmol of 9. Ϫ H NMR (CDCl3): δ ϭ 2 H, H5/H6), 3.78 (m, 2 H, CH2O spacer), 3.66 (s, 3 H, OMe), 3.49
7.64Ϫ7.19 (m, 20 H, Harom), 4.77 (AB, 2 H, CH2 Bn), 4.74 (bs, 2 (dd, 1 H, H6Ј, J5,6Ј ϭ 4.2 Hz, J6,6Ј ϭ 11.0 Hz), 2.29 (t, 2 H, CH2Cϭ
H, CH2 Bn), 4.15 (d, 1 H, H1, J1,2 ϭ 7.3 Hz), 4.13 (dd, 1 H, H2, O spacer), 1.72Ϫ0.96 (m, 18 H, CH2 spacer). Ϫ 13C{1H} NMR
J2,3 ϭ 9.0 Hz), 3.95 (m, 3 H, CH2O spacer, H5), 3.79 (dd, 1 H, H3, (CDCl3): δ ϭ 173.6 (CϭO spacer), 164.7 (CϭO Bz), 138.0, 137.3
J
3,4 ϭ 2.6 Hz), 3.74 (t, 1 H, H4, J4,5 ϭ 2.4 Hz), 3.66 (s, 3 H, OMe), (Cq Bn), 132.3Ϫ127.0 (Carom), 129.8 (Cq Bz), 101.1 (C1), 79.4, 74.7,
3.48 (dd, 1 H, H6, J5,6 ϭ 2.9 Hz, J6,6Ј ϭ 10.4 Hz), 3.39 (dd, 1 H,
72.2, 71.6 (C2/C3/C4/C5), 73.8, 71.1 (CH2 Bn), 69.0 (CH2O spacer),
H6Ј, J5,6Ј ϭ 4.0 Hz), 2.40 (bs, 1 H, OH), 2.34 (t, 2 H, CH2CϭO 60.9 (C6), 50.7 (OMe), 33.4 (CH2CϭO spacer), 28.9, 28.8, 28.6,
spacer), 1.58Ϫ1.00 (m, 18 H, CH2 spacer), 1.05 (s, 9 H, CH3 tBu).
13C{1H} NMR (CDCl3): δ ϭ 173.1 (CϭO spacer), 138.5, 138.2
28.5, 28.4, 28.3, 28.3, 25.3, 24.4 (CH2 spacer).
Ϫ
General Procedure for 2-O-Arabinosylation: A mixture of the ap-
propriate glycosyl acceptor (1.0 mmol), thioethyl -arabinofurano-
syl donor 8 (0.61 g, 1.2 mmol), powdered molecular sieves (4 A,
0.1 g) in 1,2-dichloroethane (3 ml) was stirred at 0 °C under a
continuous stream of dry nitrogen for 30 min. Subsequently, a
freshly prepared solution of NIS (0.27 g, 1.2 mmol) and TfOH (5
µl) in THF (1.0 ml) was added dropwise to the cooled solution and
the reaction mixture was stirred for 1 h. Next, the reaction mixture
was quenched with triethylamine (0.5 ml), diluted with EtOAc (50
(Cq Bn), 135.3Ϫ127.1 (Carom), 132.7 (Cq TBDPS), 103.1 (C1,
JC,H ϭ 161.2 Hz), 81.8, 74.9, 73.2, 71.3 (C2/C3/C4/C5), 74.4, 72.4
(CH2 Bn), 69.6 (CH2O spacer), 62.3 (C6), 51.1 (OMe), 33.8
(CH2CϭO spacer), 29.3, 29.3, 29.2, 29.2, 29.1, 29.0, 28.9, 25.7, 24.7
(CH2 spacer), 26.7 (CH3 tBu), 19.0 (Cq tBu). Ϫ MS (ESI): m/z ϭ
811 [M ϩ H]ϩ, 828 [M ϩ NH4]ϩ, 833 [M ϩ Na]ϩ. Ϫ C49H66O8Si
(810.5): C, 72.56; H 8.20; Si 3.46; found: C, 72.42; H 8.26; Si 3.50.
˚
General Procedure for 2-O-Benzoylation: Benzoyl chloride (0.17
ml, 1.5 mmol) was added to a stirred solution of the appropriate ml), filtered and the filtrate was washed with aq. Na2S2O3 (1.0 ,
oligomer (1.0 mmol) in pyridine (5 ml). The reaction mixture was 2 ϫ 25 ml) and aq. NaHCO3 (1.0 , 2 ϫ 25 ml). The organic layer
stirred until TLC analysis (30% EtOAc/light petroleum) revealed was dried (MgSO4) and concentrated in vacuo. The resulting yellow
complete consumption of the starting compound (2Ϫ3 h). Water oil was purified by silica gel chromatography (10Ϫ40% EtOAc/light
(1.0 ml) was added and the reaction mixture was concentrated in petroleum) and Sephadex LH-20 gel filtration (eluent: CH2Cl2/
vacuo. The residue was taken up in diethyl ether (100 ml), washed MeOH, 2:1, v/v) to give the corresponding oligosaccharide as a
with aq. NaHCO3 (1.0 , 2 ϫ 25 ml), dried (MgSO4), and concen- white foam.
trated under reduced pressure. Traces of pyridine in the residue
11-Methoxycarbonylundecanyl 2-O-(2,3,5-Tri-O-benzoyl-Ͱ--ara-
were removed by coevaporation with toluene (3 ϫ 25 ml). Further
purification was effected by silica gel chromatography (0Ϫ25%
EtOAc/light petroleum) to give the respective oligomer as a white
solid.
binofuranosyl)-3,4-di-O-benzyl-6-O-tert-butyldiphenylsilyl-β--ga-
lactopyranoside (13): Yield: 0.891 g, 0.71 mmol, 91% based on 0.632
1
g, 0.78 mmol of 10. Ϫ H NMR (CDCl3): δ ϭ 8.17Ϫ7.12 (m, 35
H, Harom), 5.58 (dd, 1 H, H3-ara, J2,3 ϭ 0.7 Hz, J3,4 ϭ 1.2 Hz),
11-Methoxycarbonylundecanyl 2-O-benzoyl-3,4-di-O-benzyl-6-O- 5.53 (d, 1 H, H1-ara, J1,2 ϭ 5.0 Hz), 4.89 (m, 1 H, H4-ara), 4.78
tert-butyl-diphenylsilyl-β--galactopyranoside (11): Yield: 1.30 g,
(dd, 1 H, H5A-ara, J4,5A ϭ 3.1 Hz, J5A,5B ϭ 12.1 Hz), 4.76 (AB, 2
1.42 mmol, 91% based on 1.26 g, 1.56 mmol of 10. Ϫ 1H NMR H, CH2 Bn), 4.74 (bs, 2 H, CH2 Bn), 4.72 (dd, 1 H, H2-ara), 4.69
(CDCl3): δ ϭ 8.62Ϫ7.19 (m, 25 H, Harom), 5.61 (dd, 1 H, H2, J1,2 ϭ (dd, 1 H, H5B-ara, J4,5B ϭ 4.7 Hz), 4.28 (d, 1 H, H1, J1,2 ϭ 7.7
8.2 Hz, J2,3 ϭ 8.9 Hz), 4.90 (AB, 2 H, CH2 Bn), 4.76 (AB, 2 H,
CH2 Bn), 4.41 (d, 1 H, H1), 4.03 (d, 1 H, H4, J3,4 ϭ 2.6 Hz), Hz), 3.78 (d, 1 H, H3), 3.75 (dd, 1 H, H6A, J5,6A ϭ 2.0 Hz, J6A,6B ϭ
3.92Ϫ3.87 (m, 3 H, H3/H5/H6), 3.71 (m, 2 H, CH2O spacer), 3.66 10.9 Hz), 3.65 (s, 3 H, OMe), 3.62 (dd, 1 H, H6B, J5,6B ϭ 3.6 Hz),
(s, 3 H, OMe), 3.48 (dd, 1 H, H6Ј, J5,6Ј ϭ 4.0 Hz, J6,6Ј ϭ 10.7 Hz), 3.47 (m, 2 H, CH2O spacer), 3.23 (dt, 1 H, H5), 2.25 (t, 2 H,
Hz), 4.21 (dd, 1 H, H2, J2,3 ϭ 9.4 Hz), 3.96 (d, 1 H, H4, J4,5 ϭ 2.3
2.29 (t, 2 H, CH2CϭO spacer), 1.78Ϫ0.84 (m, 18 H, CH2 spacer),
CH2CϭO spacer), 1.70Ϫ0.89 (m, 18 H, CH2 spacer), 1.05 (s, 9 H,
1.06 (s, 9 H, CH3 tBu). Ϫ 13C{1H} NMR (CDCl3): δ ϭ 173.0 CH3 tBu). Ϫ 13C{1H} NMR (CDCl3): δ ϭ 173.6 (CϭO spacer),
(CϭO spacer), 164.8 (CϭO Bz), 138.2, 137.4 (Cq Bn), 135.5Ϫ127.0 165.7, 165.3, 164.9 (CϭO Bz), 138.2, 137.5 (Cq Bn), 135.1Ϫ127.0
(Carom), 132.9 (Cq TBDPS), 130.1 (Cq Bz), 101.1 (C1), 79.7, 74.8, (Carom), 132.9 (Cq TBDPS), 129.0, 128.9, 128.8 (Cq Bz), 105.2 (C1-
72.5, 71.8 (C2/C3/C4/C5), 74.1, 71.6 (CH2 Bn), 69.0 (CH2O spacer),
ara, JC,H ϭ 180.2 Hz), 101.8 (C1, JC,H ϭ 161.2 Hz), 83.3, 81.8, 80.6,
94
Eur. J. Org. Chem. 1998, 91Ϫ97

Tetrameric Arabinogalactans
FULL PAPER
78.1, 74.6, 72.7, 72.6 (C2/C3/C4/C5/C2-ara/C3-ara/C4-ara), 74.5, 72.2 H6B/CHO spacer), 3.42 (dd, 1 H, H6ЈB, J6ЈA,6ЈB ϭ 11.0 Hz), 3.39
(CH2 Bn), 69.5 (CH2O spacer), 63.5 (C5-ara), 62.4 (C6), 50.9 (dd, 1 H, H3Ј), 3.05 (m, 1 H, CHO spacer), 2.34 (t, 2 H, CH2Cϭ
(OMe), 33.6 (CH2CϭO spacer), 29.3, 29.1, 29.0, 28.9, 28.9, 28.8, O spacer), 1.68Ϫ0.92 (m, 18 H, CH2 spacer), 1.07 (s, 9 H, CH3
28.7, 25.5, 24.6 (CH2 spacer), 26.5 (CH3 tBu), 18.8 (Cq tBu). Ϫ tBu). Ϫ 13C{1H} NMR (CDCl3): δ ϭ 173.9 (CϭO spacer), 164.9,
MS (ESI): m/z ϭ 1256 [M ϩ H]ϩ, 1273 [M ϩ NH4]ϩ, 1278 [M ϩ 164.8 (CϭO Bz), 138.3, 138.0, 137.4, 137.3 (Cq Bn), 135.2Ϫ127.1
Na]ϩ. Ϫ C75H86O15Si (1254.6): C, 71.75; H 6.90; Si 2.24; found: C, (Carom), 132.9 (Cq TBDPS), 130.1, 129.9 (Cq Bz), 101.2, 101.0 (C1/
71.70; H 6.96; Si 2.29.
C1Ј), 79.5, 79.5, 74.5, 73.5, 72.5, 72.2, 72.0, 71.6 (C2/C3/C4/C5/C2Ј/
C3Ј/C4Ј/C5Ј), 74.5, 74.1, 71.7, 71.3 (CH2 Bn), 68.9 (CH2O spacer),
67.9 (C6), 61.6 (C6Ј), 51.1 (OMe), 33.8 (CH2CϭO spacer), 29.1,
29.0, 28.9, 28.9, 28.8, 28.7, 28.6, 25.5, 24.6 (CH2 spacer), 26.7 (CH3
tBu), 18.9 (Cq tBu).
11-Methoxycarbonylundecanyl 2-O-(2,3,5-Tri-O-benzoyl-Ͱ--ara-
binofuranosyl)-3,4-di-O-benzyl-β--galactopyranoside (14): Yield:
0.577 g, 0.57 mmol, 80% based on 0.891 g, 0.71 mmol of 13. Ϫ H
1
NMR (CDCl3): δ ϭ 8.11Ϫ7.20 (m, 25 H, Harom), 5.56 (dd, 1 H,
H3-ara, J2,3 ϭ 0.9 Hz, J3,4 ϭ 1.3 Hz), 5.54 (d, 1 H, H1-ara, J1,2
ϭ
11-Methoxycarbonylundecanyl 2-O-Benzoyl-6-O-(2-O-benzoyl-
3,4-di-O-benzyl-β--galactopyranosyl)-3,4-di-O-benzyl-β--galac-
topyranoside (17): Yield: 0.316 g, 0.28 mmol, 76% based on 0.503
5.0 Hz), 4.92 (m, 1 H, H4-ara), 4.80 (dd, 1 H, H5A-ara, J4,5A ϭ 3.1
Hz, J5A,5B ϭ 12.0 Hz), 4.77 (AB, 2 H, CH2 Bn), 4.74 (bs, 2 H, CH2
Bn), 4.72 (dd, 1 H, H2-ara), 4.68 (dd, 1 H, H5B-ara, J4,5B ϭ 1.8
Hz), 4.34 (d, 1 H, H1, J1,2 ϭ 7.2 Hz), 4.26 (dd, 1 H, H2, J2,3 ϭ 8.0
Hz), 3.83 (d, 1 H, H4, J3,4 ϭ 2.6 Hz), 3.80Ϫ3.75 (m, 2 H, H3/H6A),
3.70 (dd, 1 H, H6B, J5,6B ϭ 3.0 Hz, J6A,6B ϭ 11.0 Hz), 3.66 (s, 3 H,
OMe), 3.50 (m, 2 H, CH2O spacer), 3.32 (dd, 1 H, H5, J5,6A ϭ 4.2
Hz), 2.28 (t, 2 H, CH2CϭO spacer), 1.72 (bs, 1 H, OH), 1.68Ϫ0.94
(m, 18 H, CH2 spacer). Ϫ 13C{1H} NMR (CDCl3): δ ϭ 172.0 (Cϭ
O spacer), 165.8, 165.7, 165.5 (CϭO Bz), 138.1, 137.5 (Cq Bn),
133.3Ϫ127.6 (Carom), 129.4, 129.3, 129.3 (Cq Bz), 105.4 (C1-ara),
102.1 (C1), 83.6, 81.9, 80.8, 78.2, 74.5, 72.7, 71.9 (C2/C3/C4/C5/C2-
ara/C3-ara/C4-ara), 74.0, 72.6 (CH2 Bn), 70.0 (CH2O spacer), 63.7
(C5-ara), 61.8 (C6), 51.2 (OMe), 33.9 (CH2CϭO spacer), 29.6, 29.3,
29.2, 29.2, 29.1, 29.1, 29.0, 25.7, 24.8 (CH2 spacer).
1
g, 0.37 mmol of 16. Ϫ H NMR (CDCl3): δ ϭ 7.98Ϫ7.10 (m, 30
H, Harom), 5.64 (dd, 1 H, H2, J1,2 ϭ 8.9 Hz, J2,3 ϭ 10.0 Hz), 5.51
(dd, 1 H, H2Ј, J1Ј,2Ј ϭ 8.0 Hz, J2Ј,3Ј ϭ 10.0 Hz), 4.87 (AB, 2 H,
CH2 Bn), 4.67 (AB, 2 H, CH2 Bn), 4.62 (AB, 2 H, CH2 Bn), 4.59
(AB, 2 H, CH2 Bn), 4.53 (d, 1 H, H1), 4.26 (d, 1 H, H1Ј), 3.91 (d,
1 H, H4, J3,4 ϭ 2.2 Hz), 3.89 (dd, 1 H, H6A, J5,6A ϭ 5.5 Hz,
J6A,6B ϭ 10.4 Hz), 3.83 (d, 1 H, H4Ј, J3Ј,4Ј ϭ 2.2 Hz), 3.76 (dd, 1
H, H6ЈA, J5Ј,6ЈA ϭ 5.6 Hz, J6ЈA,6ЈB ϭ 11.2 Hz), 3.68 (m, 2 H, H3/
H5), 3.66 (s, 3 H, OMe), 3.54 (m, 1 H, H6ЈB), 3.50Ϫ3.46 (m, 3 H,
H6B/H5Ј/CHO spacer), 3.42 (dd, 1 H, H3Ј), 3.09 (m, 1 H, CHO
spacer), 2.30 (t, 2 H, CH2CϭO spacer), 1.68Ϫ0.90 (m, 18 H, CH2
spacer), 1.40 (bs, 1 H, OH). Ϫ 13C{1H} NMR (CDCl3): δ ϭ 173.7
(CϭO spacer), 164.7, 164.6 (CϭO Bz), 138.0, 137.9, 137.3, 137.2
(Cq Bn), 135.0Ϫ127.1 (Carom), 129.8, 129.7 (Cq Bz), 101.0, 100.9
(C1/C1Ј), 79.4, 79.2, 74.7, 73.1, 72.3, 72.2, 71.7, 71.4 (C2/C3/C4/C5/
C2Ј/C3Ј/C4Ј/C5Ј), 74.1, 74.0, 71.7, 71.0 (CH2 Bn), 68.8 (CH2O
spacer), 67.3 (C6), 60.9 (C6Ј), 50.9 (OMe), 33.6 (CH2CϭO spacer),
28.9, 28.9, 28.8, 28.8, 28.6, 28.6, 28.4, 25.3, 24.5 (CH2 spacer).
11-Methoxycarbonylundecanyl 2-O-Benzoyl-3,4-di-O-benzyl-6-O-
(3,4-di-O-benzyl-6-O-tert-butyldiphenylsilyl-β--galactopyranosyl)-
β--galactopyranoside (15): Yield: 1.04 g, 0.82 mmol, 71% based
on 0.787 g, 1.16 mmol of 12. Ϫ 1H NMR (CDCl3): δ ϭ 8.11Ϫ7.10
(m, 35 H, Harom), 5.59 (dd, 1 H, H2, J1,2 ϭ 7.9 Hz, J2,3 ϭ 10.1 Hz),
4.91 (AB, 2 H, CH2 Bn), 4.74 (AB, 2 H, CH2 Bn), 4.62 (AB, 2 H,
CH2 Bn), 4.59 (AB, 2 H, CH2 Bn), 4.43 (d, 1 H, H1), 4.25 (d, 1 H,
11-Methoxycarbonylundecanyl 2-O-Benzoyl-3,4-di-O-benzyl-6-O-
(3,4-di-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-(2,3,5-tri-O-ben-
zoyl-Ͱ--arabinofuranosyl)-β--galactopyranosyl)-β--galacto-
pyranoside (18): Yield: 0.481 g, 0.28 mmol, 69% based on 0.521 g,
0.41 mmol of 15. Ϫ 13C{1H} NMR (CDCl3): δ ϭ 172.6 (CϭO
spacer), 166.1, 165.7, 165.2, 165.1 (CϭO Bz), 138.7, 138.3, 137.8,
137.7 (Cq Bn), 135.5Ϫ127.3 (Carom), 133.1 (Cq TBDPS), 130.4,
129.1 (Cq Bz), 105.8 (C1-ara, JC,H ϭ 180.0 Hz), 102.8 (C1/C1Ј,
H1Ј, J1Ј,2Ј ϭ 7.7 Hz), 4.00 (m, 1 H, H5Ј), 3.87 (d, 1 H, H4, J3,4
ϭ
2.4 Hz), 3.82 (t, 1 H, H2Ј, J2Ј,3Ј ϭ 7.8 Hz), 3.78Ϫ3.72 (m, 4 H, H3Ј/
H4Ј/H5Ј/CHO spacer), 3.69 (m, 2 H, H5/H6A), 3.66 (s, 3 H, OMe),
3.61 (dd, 1 H, H3), 3.57 (dd, 1 H, H6B, J5,6B ϭ 2.9 Hz, J6A,6B ϭ 10.7
Hz), 3.40 (m, 3 H, H6ЈA/H6ЈB/CHO spacer), 2.32 (t, 2 H, CH2CϭO
spacer), 1.74Ϫ0.92 (m, 18 H, CH2 spacer), 1.01 (s, 9 H, CH3 tBu).
J
C,H ϭ 159.9 Hz), 102.1 (C1/C1Ј, JC,H ϭ 159.7 Hz), 82.1, 80.1, 79.8,
Ϫ
13C{1H} NMR (CDCl3): δ ϭ 172.9 (CϭO spacer), 165.0 (CϭO
79.2, 78.3, 78.0, 77.6, 74.5, 73.9, 72.2, 71.7 (C2-C5/C2Ј-C5Ј/C2-C4-
ara), 74.8, 74.3, 72.6, 71.7 (CH2 Bn), 69.0 (CH2O spacer), 67.7 (C6),
63.9 (C5-ara), 60.3 (C6Ј), 51.4 (OMe), 34.0 (CH2CϭO spacer), 29.4,
29.3, 29.2, 29.1, 29.0, 28.9, 28.7, 25.8, 24.9 (CH2 spacer), 26.9 (CH3
tBu), 19.2 (Cq tBu). Ϫ MS (ESI): m/z ϭ 1702 [M ϩ H]ϩ, 1724 [M
ϩ Na]ϩ, 1740 [M ϩ K]ϩ. Ϫ C102H112O21Si (1700.7): C, 71.98; H
6.63; Si 1.65 Found: C, 71.89; H 6.69; Si 1.68.
Bz), 138.6, 138.0, 137.9, 137.4 (Cq Bn), 135.3Ϫ127.1 (Carom), 132.9
(Cq TBDPS), 130.1 (Cq Bz), 103.3 (C1/C1Ј, JC,H ϭ 162.7 Hz), 101.3
(C1/C1Ј, JC,H ϭ 158.5 Hz), 81.8, 79.6, 74.6, 73.8, 73.0, 72.1, 71.7,
71.2 (C2/C3/C4/C5/C2Ј/C3Ј/C4Ј/C5Ј), 74.5, 74.0, 72.3, 72.2 (CH2 Bn),
69.4 (CH2O spacer), 68.2 (C6), 61.6 (C6Ј), 51.2 (OMe), 33.8
(CH2CϭO spacer), 29.2, 29.1, 29.0, 28.9, 28.7, 28.6, 28.4, 25.6, 24.7
(CH2 spacer), 26.7 (CH3 tBu), 19.0 (Cq tBu). Ϫ MS (ESI): m/z ϭ
1258 [M ϩ H]ϩ, 1280 [M ϩ Na]ϩ. Ϫ C76H92O14Si (1256.6): C,
72.58; H 7.37; Si 2.23; found: C, 72.54; H 7.50; Si 2.21.
11-Methoxycarbonylundecanyl 2-O-Benzoyl-3,4-di-O-benzyl-6-O-
(3,4-di-O-benzyl-2-O-(2,3,5-tri-O-benzoyl-Ͱ--arabinofuranosyl)-β-
-galactopyranosyl)-β--galactopyranoside (19): Yield: 0.332 g,
0.23 mmol, 81% based on 0.481 g, 0.28 mmol of 18. Ϫ 13C{1H}
NMR (CDCl3): δ ϭ 173.0 (CϭO spacer), 165.8, 165.4, 164.8, 164.7
(CϭO Bz), 138.0, 137.4, 137.3, 137.2 (Cq Bn), 132.6Ϫ127.0 (Carom),
129.9, 129.8, 128.8, 128.7 (Cq Bz), 105.3 (C1-ara), 101.7, 101.0 (C1/
C1Ј), 81.6, 78.3, 76.9, 76.8, 76.1, 74.6, 73.3, 72.7, 72.3, 71.7, 70.9
(C2-C5/C2Ј-C5Ј/C2-C4-ara), 74.1, 73.9, 72.1, 71.4 (CH2 Bn), 70.0
(CH2O spacer), 68.8 (C6), 63.4 (C5-ara), 61.2 (C6Ј), 51.0 (OMe),
33.6 (CH2CϭO spacer), 29.0, 28.9, 28.8, 28.8, 28.7, 28.6, 28.4, 25.4,
24.5 (CH2 spacer).
11-Methoxycarbonylundecanyl 2-O-Benzoyl-6-O-(2-O-benzoyl-
3,4-di-O-benzyl-6-O-tert-butyldiphenylsilyl-β--galactopyranosyl)-
3,4-di-O-benzyl-β--galactopyranoside (16): Yield: 0.503 g, 0.37
mmol, 90% based on 0.521 g, 0.41 mmol of 15. Ϫ 1H NMR
(CDCl3): δ ϭ 7.91Ϫ7.14 (m, 40 H, Harom), 5.59 (dd, 1 H, H2, J1,2 ϭ
7.9 Hz, J2,3 ϭ 10.0 Hz), 5.47 (dd, 1 H, H2Ј, J1Ј,2Ј ϭ 8.0 Hz, J2Ј,3Ј
ϭ
10.0 Hz), 4.93 (AB, 2 H, CH2 Bn), 4.67 (AB, 2 H, CH2 Bn), 4.52
(AB, 2 H, CH2 Bn), 4.48 (d, 1 H, H1), 4.43 (AB, 2 H, CH2 Bn),
4.21 (d, 1 H, H1Ј), 4.09 (d, 1 H, H4, J3,4 ϭ 2.3 Hz), 3.90 (t, 1 H,
H5, J5,6A ϭ J5,6B ϭ 5.9 Hz), 3.80 (m, 2 H, H6A/H6ЈA), 3.73 (d, 1 H,
H4Ј, J3Ј,4Ј ϭ 2.6 Hz), 3.67 (s, 3 H, OMe), 3.64 (dd, 1 H, H3), 3.61
11-Methoxycarbonylundecanyl 3,4-Di-O-benzyl-6-O-(3,4-di-O-
(dd, 1 H, H5Ј, J5Ј,6ЈA ϭ 4.0 Hz, J5Ј,6ЈB ϭ 6.2 Hz), 3.48 (m, 2 H, benzyl-6-O-tert-butyldiphenylsilyl-β--galactopyranosyl)-2-O-
Eur. J. Org. Chem. 1998, 91Ϫ97
95

J. H. van Boom et al.
FULL PAPER
(2,3,5-tri-O-benzoyl-Ͱ--arabinofuranosyl)-β--galactopyranoside
General Procedure for Deprotection of the Tetrasaccharides:
(20): Yield: 0.623 g, 0.39 mmol, 68% based on 0.577 g, 0.57 mmol Tetra-n-butylammonium fluoride (1.0  solution in THF, 0.15 ml,
of 14. Ϫ 13C{1H} NMR (CDCl3): δ ϭ 171.9 (CϭO spacer), 165.8,
0.15 mmol) was added to a stirred solution of the appropriate tetra-
165.4, 165.0 (CϭO Bz), 138.5, 137.9, 137.4, 137.3 (Cq Bn), mer (0.10 mmol) in THF (1 ml). When TLC-analysis (50% EtOAc/
135.2Ϫ127.1 (Carom), 132.8 (Cq TBDPS), 129.0, 128.8, 128.7 (Cq light petroleum) showed complete disappearance of the starting
Bz), 105.2 (C1-ara, JC,H ϭ 178.8 Hz), 103.3 (C1/C1Ј, JC,H ϭ 158.6 material (3Ϫ5 h) the reaction mixture was diluted with EtOAc (25
Hz), 101.8 (C1/C1Ј, JC,H ϭ 161.0 Hz), 83.2, 81.9, 81.8, 81.7, 80.7,
ml) and washed with sat. aq. NaCl (3 ϫ 10 ml). The organic phase
80.6, 78.1, 74.5, 73.0, 71.2, 71.1 (C2-C5/C2Ј-C5Ј/C2-C4-ara), 73.9, was dried (MgSO4), filtered through a bed of silica (5 g), and con-
73.8, 73.2, 72.3 (CH2 Bn), 69.7 (CH2O spacer), 66.7 (C6), 62.9 (C5- centrated in vacuo. To a stirred solution of the residue in MeOH/
ara), 61.5 (C6Ј), 51.0 (OMe), 33.7 (CH2CϭO spacer), 29.4, 29.3,
CH2Cl2 (5 ml, 2:1, v/v) was added KOtBu (11 mg, 0.10 mmol).
29.2, 29.1, 29.0, 28.9, 28.8, 25.6, 24.6 (CH2 spacer), 26.6 (CH3 tBu), After 30 min, the reaction was terminated by addition of Dowex
18.8 (Cq tBu). Ϫ MS (ESI): m/z ϭ 1598 [M ϩ H]ϩ, 1620 [M ϩ 50WX4-Hϩ (100 mg). The ion-exchange resin was filtered off and
Na]ϩ. Ϫ C95H108O20Si (1596.7): C, 71.41; H 6.81; Si 1.76; found:
C, 71.32; H 6.86; Si 1.79.
the filtrate was concentrated in vacuo. The resulting colorless oil
was dissolved in tBuOH/H2O (3:1, v/v, 4 ml) after which palladium
on carbon (10%, 100 mg) was added. The heterogeneous mixture
was hydrogenated at elevated pressure (3 atm.) in a Parr apparatus
for 12 h and subsequently filtered. The filtrate was concentrated
under reduced pressure and subjected to Pharmacia HW-40 gel fil-
tration (eluent: MeOH/H2O, 1:1, v/v). Lyophilization of the appro-
priate fractions afforded the corresponding spacer-containing tetra-
saccharide as a white fluffy solid.
11-Methoxycarbonylundecanyl 3,4-Di-O-benzyl-6-O-(3,4-di-O-
benzyl-β--galactopyranosyl)-2-O-(2,3,5-tri-O-benzoyl-Ͱ--ara-
binofuranosyl)-β--galactopyranoside (21): Yield: 0.403 g, 0.30
mmol, 76% based on 0.623 g, 0.39 mmol of 20. Ϫ 13C{1H} NMR
(CDCl3): δ ϭ 173.2 (CϭO spacer), 166.0, 165.3, 165.1 (CϭO Bz),
138.1, 137.5, 137.2, 137.1 (Cq Bn), 133.2Ϫ127.4 (Carom), 129.9,
129.7, 129.2 (Cq Bz), 105.3 (C1-ara), 103.4, 101.9 (C1/C1Ј), 83.3,
81.9, 81.8, 81.7, 80.7, 78.1, 74.8, 73.5, 72.6, 72.2, 71.3 (C2-C5/C2Ј-
11-Methoxycarbonylundecanyl 6-O-(6-O-(2-O-(Ͱ--Arabinofura-
C5Ј/C2-C4-ara), 74.1, 74.0, 72.5, 72.4 (CH2 Bn), 69.9 (CH2O nosyl)-β--galactopyranosyl)-β--galactopyranosyl)-β--galac-
spacer), 67.2 (C6), 63.6 (C5-ara), 61.5 (C6Ј), 51.2 (OMe), 33.9 topyranoside (1): Yield: 89.5 mg, 0.11 mmol, 66% based on 0.334
(CH2CϭO spacer), 29.3, 29.3, 29.1, 29.0, 29.0, 28.9, 28.6, 25.7, 24.7 g, 0.16 mmol of 23. Ϫ [α]D ϭ ϩ4.7 (c ϭ 0.2, H2O). Ϫ 13C{1H}
(CH2 spacer).
NMR (D2O/MeOD, 4:1, v/v): δ ϭ 175.1 (CϭO spacer), 109.3 (C1-
ara), 104.2, 104.0, 103.3 (C1/C1Ј/C1ЈЈ), 85.9, 81.8, 78.1, 76.6, 74.8,
74.5, 74.2, 74.1, 74.0, 73.9, 73.8, 71.9, 71.8, 69.9, 69.7 (C2-C5/C2Ј-
C5Ј/C2ЈЈ-C5ЈЈ/C2-ara/C3-ara/C4-ara), 71.3 (CH2O spacer), 69.5, 69.4
(C6/C6Ј), 62.6 (C5-ara), 61.9 (C6ЈЈ), 52.6 (OMe), 34.7 (CH2CϭO
spacer), 30.1, 30.1, 29.8, 29.7, 29.6, 29.5, 29.4, 26.4, 25.6 (CH2
spacer). Ϫ MS (ESI): m/z ϭ 849 [M ϩ H]ϩ; m/2z ϭ 425 [M ϩ
2 H]2ϩ. Ϫ C36H64O22 (848.4): C, 50.94; H 7.60; found: C, 50.91;
H 7.62.
11-Methoxycarbonylundecanyl 2-O-Benzoyl-3,4-di-O-benzyl-6-O-
(2-O-benzoyl-6-O-(3,4-di-O-benzyl-6-O-tert-butyldiphenylsilyl-β--
galactopyranosyl)-3,4-di-O-benzyl-β--galactopyranosyl)-β--
galactopyranoside (22): Yield: 0.319 g, 0.19 mmol, 67% based on
0.316 g, 0.28 mmol of 17. Ϫ 13C{1H} NMR (CDCl3): δ ϭ 173.8
(CϭO spacer), 164.8, 164.7 (CϭO Bz), 138.4, 138.1, 138.1, 138.0,
137.8, 137.4 (Cq Bn), 135.1Ϫ127.0 (Carom), 132.9, 132.7 (Cq
TBDPS), 130.0, 129.9 (Cq Bz), 103.1 (C1/C1Ј/C1ЈЈ, JC,H ϭ 161.2
Hz), 101.1 (C1/C1Ј/C1ЈЈ, JC,H ϭ 156.8 Hz), 101.0 (C1/C1Ј/C1ЈЈ
C,H ϭ 156.7 Hz), 81.8, 79.0, 78.8, 78.7, 73.3, 72.9, 72.8, 72.7, 71.7,
,
11-Methoxycarbonylundecanyl 2-O-Benzoyl-3,4-di-O-benzyl-6-O-
(2-O-(2,3,5-tri-O-benzoyl-Ͱ--arabinofuranosyl)-6-O-(3,4-di-O-
J
71.5, 70.9, 70.4 (C2-C5/C2Ј-C5Ј/C2ЈЈ-C5ЈЈ), 74.4, 73.6, 72.3, 72.2, 71.2, benzyl-6-O-tert-butyldiphenyl-silyl-β--galactopyranosyl)-3,4-di-O-
71.0 (CH2 Bn), 70.0 (CH2O spacer), 69.2, 68.9 (C6/C6Ј), 61.8 (C6ЈЈ), benzyl-β--galactopyranosyl)-β--galactopyranoside (24): Yield:
51.0 (OMe), 33.7 (CH2CϭO spacer), 29.0, 28.9, 28.8, 28.8, 28.7,
0.296 g, 0.14 mmol, 63% based on 0.332 g, 0.23 mmol of 19. Ϫ
28.7, 28.5, 25.4, 24.6 (CH2 spacer), 26.6 (CH3 tBu), 18.8 (Cq tBu). 13C{1H} NMR (CDCl3): δ ϭ 172.8 (CϭO spacer), 166.0, 165.6,
Ϫ MS (ESI): m/z ϭ 1704 [M ϩ H]ϩ, 1726 [M ϩ Na]ϩ, 1742 [M ϩ 165.0, 164.8, (CϭO Bz), 138.6, 138.3, 138.0, 137.9, 137.6, 137.5 (Cq
K]ϩ. Ϫ C103H118O20Si (1702.8): C, 72.60; H 6.98; Si 1.65; found:
C, 72.54; H 7.02; Si 1.67.
Bn), 135.3Ϫ127.3 (Carom), 133.4 (Cq TBDPS), 130.2, 129.0, 128.9,
128.8 (Cq Bz), 105.5 (C1-ara, JC,H ϭ 178.8 Hz), 103.1 (C1/C1Ј/C1ЈЈ
,
JC,H ϭ 159.7 Hz), 101.8 (C1/C1Ј/C1ЈЈ, JC,H ϭ 161.9 Hz), 101.2 (C1/
C1Ј/C1ЈЈ, JC,H ϭ 161.1 Hz), 82.0, 80.0, 79.9, 77.8, 77.6, 76.8, 73.6,
11-Methoxycarbonylundecanyl 2-O-Benzoyl-3,4-di-O-benzyl-6-O-
(2-O-benzoyl-6-O-(3,4-di-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-
(2,3,5-tri-O-benzoyl-Ͱ--arabinofuranosyl)-3,4-di-O-benzyl-β--galac-
topyranosyl)-3,4-di-O-benzyl-β--galactopyranosyl)-β--galactopy-
ranoside (23): Yield: 0.334 g, 0.16 mmol, 82% based on 0.319 g,
0.19 mmol of 22. Ϫ 13C{1H} NMR (CDCl3): δ ϭ 173.9 (CϭO
spacer), 165.9, 165.5, 164.9, 164.8, 164.5 (CϭO Bz), 138.1, 138.0,
137.9, 137.9, 137.4, 137.3 (Cq Bn), 135.2Ϫ127.0 (Carom), 132.9,
132.8 (Cq TBDPS), 130.0, 129.9, 129.7 (Cq Bz), 105.3 (C1-ara,
JC,H ϭ 177.9 Hz), 101.7 (C1/C1Ј/C1ЈЈ, JC,H ϭ 161.4 Hz), 101.1 (C1/
C1Ј/C1ЈЈ, JC,H ϭ 158.2 Hz), 101.0 (C1/C1Ј/C1ЈЈ, JC,H ϭ 158.3 Hz),
73.4, 72.9, 72.7, 71.8, 71.6, 71.1, 70.8, 70.6 (C2-C5/C2Ј-C5Ј/C2ЈЈ-C5ЈЈ
/
C2-ara/C3-ara/C4-ara), 74.7, 74.3, 73.8, 72.4, 72.2, 71.6 (CH2 Bn),
69.1 (CH2O spacer), 68.4, 67.2 (C6/C6Ј), 63.7 (C5-ara), 61.6 (C6ЈЈ),
51.2 (OMe), 33.9 (CH2CϭO spacer), 29.3, 29.2, 29.1, 29.0, 28.9,
28.9, 28.8, 25.7, 24.8 (CH2 spacer), 26.8 (CH3 tBu), 19.0 (Cq tBu).
Ϫ MS (ESI): m/z ϭ 2044 [M ϩ H]ϩ; m/2z ϭ 1022 [M ϩ 2 H]2ϩ
.
Ϫ C122H134O26Si (2042.9): C, 71.67; H 6.61; Si 1.37; found: C,
71.54; H 6.64; Si 1.40.
11-Methoxycarbonylundecanyl
6-O-(2-O-(Ͱ--Arabinofurano-
83.1, 81.6, 80.7, 79.6, 79.3, 78.4, 78.2, 78.1, 74.6, 74.5, 73.1, 72.6, syl)-6-O-(β--galactopyranosyl)-β--galactopyranosyl)-β--
71.5, 71.4, 70.6 (C2-C5/C2Ј-C5Ј/C2ЈЈ-C5ЈЈ/C2-ara/C3-ara/C4-ara), galactopyranoside (2): Yield: 88.1 mg, 0.10 mmol, 70% based on
74.5, 74.3, 73.8, 72.6, 72.5, 72.0 (CH2 Bn), 71.0 (CH2O spacer),
69.0, 66.7 (C6/C6Ј), 63.6 (C5-ara), 61.3 (C6ЈЈ), 51.1 (OMe), 33.8 NMR (D2O/MeOD, 4:1, v/v): δ ϭ 175.8 (CϭO spacer), 109.6 (C1-
(CH2CϭO spacer), 29.2, 29.1, 29.0, 28.9, 28.8, 28.6, 28.4, 25.5, 24.6
ara), 105.3, 104.7, 104.0 (C1/C1Ј/C1ЈЈ), 87.2, 82.0, 79.0, 76.7, 76.0,
(CH2 spacer), 26.7 (CH3 tBu), 19.0 (Cq tBu). Ϫ MS (ESI): m/z ϭ 75.2, 75.1, 75.0, 74.8, 74.7, 72.5, 72.4, 70.3, 70.2, 70.0 (C2-C5/C2Ј-
2148 [M ϩ H]ϩ; m/2z ϭ 1075 [M ϩ 2 H]2ϩ. Ϫ C129H138O27Si C5Ј/C2ЈЈ-C5ЈЈ/C2-ara/C3-ara/C4-ara), 71.0 (CH2O spacer), 69.6, 69.4
(2146.9): C, 72.11; H 6.47; Si 1.31 Found: C, 72.08; H 6.55; Si 1.31. (C6/C6Ј), 63.2 (C5-ara), 62.6 (C6ЈЈ), 52.4 (OMe), 34.8 (CH2CϭO
0.296 g, 0.14 mmol of 24. Ϫ [α]D ϭ ϩ5.9 (c ϭ 0.2, H2O). 13C{1H}
96
Eur. J. Org. Chem. 1998, 91Ϫ97

Tetrameric Arabinogalactans
FULL PAPER
spacer), 30.9, 30.7, 30.6, 30.6, 30.5, 30.3, 30.2, 27.1, 26.0 (CH2 ara), 105.8, 105.4, 104.2 (C1/C1Ј/C1ЈЈ), 86.7, 83.4, 78.9, 77.9, 77.5,
spacer). Ϫ MS (ESI): m/z ϭ 849 [M ϩ H]ϩ; m/2z ϭ 425 [M ϩ 77.4, 76.0, 75.7, 75.4, 75.3, 75.2, 75.1, 75.0, 73.1, 71.0 (C2-C5/C2Ј-
2 H]2ϩ. Ϫ C36H64O22 (848.4): C, 50.94; H 7.60; found: C, 50.90; C5Ј/C2ЈЈ-C5ЈЈ/C2-ara/C3-ara/C4-ara), 71.7 (CH2O spacer), 69.8, 69.7
H 7.65.
(C6/C6Ј), 63.3 (C5-ara), 61.7 (C6ЈЈ), 54.1 (OMe), 36.1 (CH2CϭO
spacer), 31.4, 31.3, 31.2, 31.1, 31.0, 30.9, 27.9, 27.4, 26.9 (CH2
spacer). Ϫ MS (ESI): m/z ϭ 849 [M ϩ H]ϩ; m/2z ϭ 425 [M ϩ
2 H]2ϩ. Ϫ C36H64O22 (848.4): C, 50.94; H 7.60; found: C, 50.87;
H 7.69.
11-Methoxycarbonylundecanyl 3,4-Di-O-benzyl-6-O-(6-O-(3,4-
di-O-benzyl-6-O-tert-butyldiphenylsilyl-β--galactopyranosyl)-3,4-
di-O-benzyl-β--galactopyranosyl)-2-O-(2,3,5-tri-O-benzoyl-Ͱ--
arabinofuranosyl)-β--galactopyranoside (25): Yield: 0.351 g, 0.18
mmol, 60% based on 0.403 g, 0.30 mmol of 21. Ϫ 13C{1H} NMR
(CDCl3): δ ϭ 172.9 (CϭO spacer), 166.0, 165.5, 165.1 (CϭO Bz),
138.6, 138.2. 138.2, 138.0, 137.9, 137.5 (Cq Bn), 135.3Ϫ127.2 (Ca-
rom), 133.2 (Cq TBDPS), 129.4, 129.3, 129.2 (Cq Bz), 105.3 (C1-ara,
JC,H ϭ 178.8 Hz), 103.3 (C1/C1Ј/C1ЈЈ, JC,H ϭ 156.9 Hz), 103.2 (C1/
C1Ј/C1ЈЈ, JC,H ϭ 157.0 Hz), 101.9 (C1/C1Ј/C1ЈЈ, JC,H ϭ 161.2 Hz),
83.3, 81.9, 81.8, 81.7, 81.6, 80.7, 78.1, 74.6, 73.5, 73.4, 73.0, 72.5,
72.2, 71.1, 71.0 (C2-C5/C2Ј-C5Ј/C2ЈЈ-C5ЈЈ/C2-ara/C3-ara/C4-ara),
74.5, 74.2, 74.0, 72.4, 72.2, 72.1 (CH2 Bn), 69.9 (CH2O spacer),
68.0, 67.4 (C6/C6Ј), 63.7 (C5-ara), 61.5 (C6ЈЈ), 51.1 (OMe), 33.8
(CH2CϭO spacer), 29.5, 29.4, 29.3, 29.2, 29.1, 29.0, 28.9, 25.7, 24.7
(CH2 spacer), 26.7 (CH3 tBu), 18.9 (Cq tBu). Ϫ MS (ESI): m/z ϭ
1940 [M ϩ H]ϩ; m/2z ϭ 970 [M ϩ 2 H]2ϩ. Ϫ C115H130O25Si
(1938.9): C, 71.19; H 6.75; Si 1.45; found: C, 71.12; H 6.82; Si 1.46.
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[1b]
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11-Methoxycarbonylundecanyl 2-O-(Ͱ--Arabinofuranosyl)-6-O-
(6-O-(β--galactopyranosyl)-β--galactopyranosyl)-β--galacto-
pyranoside (3): Yield: 97.7 mg, 0.12 mmol, 64% based on 0.351 g,
0.18 mmol of 25. Ϫ [α]D ϭ ϩ13.6 (c ϭ 0.2, H2O). Ϫ 13C{1H}
NMR (D2O/MeOD, 4:1, v/v): δ ϭ 178.6 (CϭO spacer), 110.5 (C1-
G. H. Veeneman, S. H. van Leeuwen, J. H. van Boom, Tetra-
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Prof. Dr. P. Albersheim, Complex Carbohydrate Research
Center, University of Georgia, Athens, U.S.A.
[97225]
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97