An efficient and practical synthesis of β-(1→3)-linked xylooligosaccharides

Article abstract of DOI:10.1016/S0008-6215(02)00285-9

A facile and practical method was developed for the synthesis of β-(1→3)-linked xylooligosaccharides. Dibezoylation of allyl α-D-xylopyranoside (1) afforded 2,4-dibenzoate 6 as the major product. Chloroacetylation of 6, followed by deallylation and trichloroacetimidation, gave a 1:3 α/β imidate (10 and 11) mixture. Coupling of the imidate mixture with 6 gave a disaccharide 13, whose dechloroacetylation afforded the disaccharide acceptor 16. Condensation of perbenzoylated xylosyl α/β imidate (7 and 8) mixture with 6 gave the disaccharide 12. Deallylation of 12, followed by trichloroacetimidation, furnished the disaccharide donor as a 1:1 α/β mixture. Coupling of the disaccharide donor mixture with the disaccharide acceptor 16 yielded the tetrasaccharide 17. Reiteration of deallylation and trichloroacetimidation transformed 17 to the tetrasaccharide donor mixture. Condensation of the tetrasaccharide donor mixture with the acceptor 16 gave the hexasaccharide 21. Debenzoylation with saturated ammonia-methanol afforded β-(1→3)-linked allyl xylotetraoside and xylohexaoside.

Full text of DOI:10.1016/S0008-6215(02)00285-9

Carbohydrate Research 337 (2002) 2335–2341
www.elsevier.com/locate/carres
Note
An efficient and practical synthesis of b-(1“3)-linked
xylooligosaccharides
Langqiu Chen, Fanzuo Kong*
Research Center for Eco-En6ironmental Sciences, Chinese Academy of Sciences, PO Box 2871, Beijing 100085, China
Received 11 March 2002; accepted 27 March 2002
Dedicated to Professor Derek Horton on the occasion of his 70th birthday
Abstract
A facile and practical method was developed for the synthesis of b-(1“3)-linked xylooligosaccharides. Dibezoylation of allyl
D-xylopyranoside (1) afforded 2,4-dibenzoate 6 as the major product. Chloroacetylation of 6, followed by deallylation and
a-
trichloroacetimidation, gave a 1:3 a/b imidate (10 and 11) mixture. Coupling of the imidate mixture with 6 gave a disaccharide
13, whose dechloroacetylation afforded the disaccharide acceptor 16. Condensation of perbenzoylated xylosyl a/b imidate (7 and
8) mixture with 6 gave the disaccharide 12. Deallylation of 12, followed by trichloroacetimidation, furnished the disaccharide
donor as a 1:1 a/b mixture. Coupling of the disaccharide donor mixture with the disaccharide acceptor 16 yielded the
tetrasaccharide 17. Reiteration of deallylation and trichloroacetimidation transformed 17 to the tetrasaccharide donor mixture.
Condensation of the tetrasaccharide donor mixture with the acceptor 16 gave the hexasaccharide 21. Debenzoylation with
saturated ammonia–methanol afforded b-(1“3)-linked allyl xylotetraoside and xylohexaoside. © 2002 Elsevier Science Ltd. All
rights reserved.
Keywords: Oligosaccharide; Xylose; Regioselective synthesis
b-(1“3)-Linked xylan occurs in algae cell-wall
polysaccharides. Treatment of b-(1“3)-linked xylan
from Caulerpa racemesa laete-6irens with b-(1“3)-xy-
lanase of Vibrio sp. AX-4 gave b-(1“3)-linked xy-
looligosaccahrides with average DP 55. These
xyloolgosaccharides show in vitro 70% inhibition of
DNA synthesis of human leukemia HL 60 cells, and
thus have potential use as cancer cell apoptosis induc-
ers.1 For investigation of structure–bioactivity relation-
ships among xylooligosaccharides, we report herein a
concise and efficient synthesis of b-(1“3)-linked
xylooligosaccahrides.
However, to the best of our knowledge, there have
rarely been reports regarding the syntheses of b-(1“3)-
linked xylooligosaccharides.3 Perhaps, the difficulty for
regioselective protection4 of xylose limits the use of
xylose in the glycosylation. An a-linked trisaccharide,
a-D-Xylp-(1“3)-a-
D
-Xylp-(1“3)-D-Glcp, and its ser-
ine conjugate have been synthesized with benzylated
xylose derivatives.5 We present herein the syntheses of
b-(1“3)-linked xylopyranose di-, tetra-, and hexamers
using peracylated trichloroacetimidates6 as the donors
and corresponding acylated xylose derivatives as the
acceptors.
b-(1“4)-Linked xylans as the main components of
arabinoxylans widely occur in the cell walls of grass
and legume forage plants, and the synthesis of b-(1“
4)-linked xylooligosaccharides have been reported.2
As outlined in Scheme 1, allyl a- -xylopyranoside (1)
D
was dibenzoylated to afford a mixture of 2,3,4-triben-
zoate 4 (25%), 2,3-dibenzoate 5 (20%), and 2,4-diben-
zoate 6 (45%), and unidentified byproducts (10%).
Compounds 4, 5, and 6 were identified by their 1H
NMR spectra, which gave a multiplet for H-4, and a
triplet with J2,3=J3,4 9.8 Hz for H-3, and a doublet of
doublets with J1,2 3.7 Hz, J2,3 9.8 Hz for H-2, respec-
tively. The 2,3-dibenzoate 5 showed H-2 and H-3
* Corresponding author. Tel.: +86-10-629-36613; fax: +
86-10-629-23563
E-mail address: fzkong@mail.rcees.ac.cn (F. Kong).
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00285-9

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L. Chen, F. Kong / Carbohydrate Research 337 (2002) 2335–2341
Scheme 1. Reagents and conditions: (a) PhCOCl, Pyr, rt. (b) Ac2O, Pyr, rt. (c) (i) PdCl2, CH3OH, 40 °C; (ii) CCl3CN, CH2Cl2,
K2CO3, rt. (d) ClCH2COCl, Pyr, rt. (e) TMSOTf, CH2Cl2, −25 °C to rt. (f) Thiourea, EtOH, CH2Cl2, reflux. (g) NH3–CH3OH,
rt.

L. Chen, F. Kong / Carbohydrate Research 337 (2002) 2335–2341
2337
moved downfield, while the 2,4-dibenzoate 6 showed
H-2 and H-4 moved downfield. An alternative prepara-
tion of 4, 5, and 6 was also successful. Thus, monoben-
zoylation of 1 with benzoyl chloride in pyridine
yield as the sole product. Finally, debenzoylation of 17
and 21 in saturated ammonia–methanol solution gave
the target tetrasaccharide 20 and the hexasaccharide 22
as their allyl glycosides. The use of ammonia–methanol
solution instead of sodium methoxide–methanol en-
sured the mildness and completion of the debenzoyla-
tion. The bioassay of the synthetic xylotetraose and
hexaose is in progress.
In summary, we present herewith a very facile and
convergent synthesis of b-(1“3)-linked xylooligosac-
charides. It should be possible to carry out large-scale
preparation of the xylotetraose, xylohexaose and higher
xylooligosaccharides employing this method.
afforded allyl 3-O-benzoyl-a- -xylopyranoside (2) in
D
high yield (75%). Subsequent monobenzoylation of 2
gave 4, 5, and 6 in 24, 19, and 45%, respectively,
together with 12% unidentified byproducts. It was
noted that during bezoylation of 2, benzoyl group
migration occurred as the 2,4-dibenzoate 6 was the
major product. With the tribenzoate 4 and the 2,4-
dibenzoate 6 in hand, the b-(1“3)-linked xylooligosac-
charides were readily constructed, since the former was
easily transformed to a donor by activation of C-1, and
the latter was an acceptor for the disaccharide synthesis
and used to prepare the disaccharide acceptor. There-
fore, deallylation of 4 with PdCl2 in methanol,7 fol-
lowed by trichloroacetimidation with Cl3CCN, gave an
inseparable mixture of 2,3,4-tri-O-benzoyl-a- (7) and
1. Experimental
General methods.—Melting points were determined
with a ‘Mel-Temp’ apparatus. Optical rotations were
determined with a Perkin–Elmer model 241-MC auto-
matic polarimeter for solutions in a 1-dm, jacketed cell.
1H NMR spectra were recorded with Varian XL-400
and Varian XL-200 spectrometers, for solutions in
CDCl3 with tetramethylsilane (Me4Si) as the internal
standard or for solutions in D2O with acetone as the
internal standard. Mass spectra were recorded with a
VG PLATFORM mass spectrometer using the electro-
spray-ionization mode. The progress of all reactions
was followed by thin-layer chromatography (TLC) that
was performed on silica gel HF with detection by
charring with 30% (v/v) sulfuric acid in methanol or by
UV detection. Column chromatography was conducted
by elution of a column (8×100 mm, 16×240 mm,
18×300 mm, 35×400 mm) of silica gel (100–200
mesh) and EtOAc–petroleum ether (bp 60–90 °C) as
the eluent. Analytical LC was performed with a Gilson
HPLC consisting of a pump (model 306), stainless steel
column packed with silica gel (Spherisorb SiO2, 10×
300 mm or 4.6×250 mm), differential refractometer
(132-RI detector) and UV/vis detector (model 118).
EtOAc–petroleum ether (bp 60–90 °C) was used as the
eluent at a flow rate of 1–4 mL/min. Solutions were
concentrated at a temperature B60 °C under dimin-
ished pressure.
-b- -xylopyranosyl trichloroacetimidate (8) in 3:17 ra-
D
tio. It was noted that the 1H NMR spectrum of 7
4
indicated a C1 conformation as judged from J1,2 3.6
1
Hz, J2,3=J3,4 10 Hz, while the H NMR spectrum of 8
1
indicated a C4 conformation, i.e., ‘tetra axial’ substitu-
tion form, as judged from J1,2 2.6 Hz, J2,3=J3,4 4.2 Hz.
The mixture of 7 and 8 was coupled with the acceptor
6 in the presence of TMSOTf to afford a unique
disaccharide 12 in high yield (85%). Deallylation of 12,
followed by trichloroacetimidation, again gave an in-
separable mixture of 2,3,4-tri-O-benzoyl-(1“3)-2,4-di-
O-benzoyl-a- (14) and -b-
D-xylopyranosyl trichloro-
acetimidate (15) in a ratio of ꢀ1:1. The disaccharide
acceptor was obtained from allyl 2,4-di-O-benzoyl-a-D-
xylopyranoside (6). Thus, chloroacetylation of 6 with
chloroacetyl chloride in pyridine furnished allyl 2,4-di-
O-benzoyl-3-O-chloroacetyl-a- -xylopyranoside (9) in
D
high yield (96%), and subsequent deallylation and
trichloroacetimidation gave an inseparable mixture
(80% for two steps) of 2,4-di-O-benzoyl-3-O-
chloroacetyl-a-
(10)
and
-b-D-xylopyranosyl
trichloroacetimidate (11) in 1:3 ratio. Condensation of
the mixture of 10 and 11 with the acceptor 6 furnished
a unique b-(1“3)-linked disaccharide 13 in 85% yield.
Dechloroacetylation of 13 with thiourea gave the disac-
charide acceptor 16 in satisfactory yield (80%). Then
coupling of the disaccharide donor mixture of 14 and
15 with the disaccharide acceptor 16 gave b-(1“3)-
linked tetrasaccharide 17 as the sole product in 80%
yield. Reiteration of deallylation and trichloroacetimi-
dation transformed 17 in 80% yield to a 1:1 mixture of
Allyl
2,4-di-O-acetyl-3-O-benzoyl-h-D-xylopyran-
oside (3).—To a solution of 1 (3.80 g, 20.0 mmol) in
pyridine (10 mL) was added benzoyl chloride (2.32 mL,
20.0 mmol). The reaction mixture was stirred overnight
at rt. TLC (EtOAc) indicated that the reaction was
complete. Water (50 mL) was added, and the mixture
was extracted with CH2Cl2 (3×50 mL). The extract
was washed with M HCl and satd aq NaHCO3, dried
(Na2SO4) and concentrated. Purification by flash chro-
matography (EtOAc) gave 2 (4.41 g, 75%). To a solu-
tion of 2 (0.30 g, 1.0 mmol) in pyridine (5 mL) was
added Ac2O (0.5 mL, 5.3 mmol). The reaction mixture
anomers, 2,3,4-tri-O-benzoyl-b-
3)-2,4-di-O-benzoyl-b- -xylopyranosyl-(1“3)-2,4-di-
O-benzoyl-b- -xylopyranosyl-(1“3)-2,4-di-O-ben-
zoyl-a- - (18) and -b- -xylopyranosyl trichloroacetimi-
D-xylopyranosyl-(1“
D
D
D
D
date (19). Condensation of 18 and 19 with the acceptor
16 gave sole b-(1“3)-linked hexasaccharide 21 in 75%

2338
L. Chen, F. Kong / Carbohydrate Research 337 (2002) 2335–2341
was stirred overnight at rt. TLC (3:1 petroleum ether–
EtOAc) indicated that the reaction was complete. Wa-
ter (20 mL) was added, and the mixture was extracted
with CH2Cl2 (3×20 mL). The extract was washed with
M HCl and satd aq NaHCO3, dried (Na2SO4) and
concentrated. Purification by flash chromatography (3:1
petroleum ether–EtOAc) gave 3 (0.36 g, 95%) as a
Calcd for C22H22O7: C, 66.33; H, 5.53. Found: C, 66.19;
H, 5.55. 6: [h]D +75.3° (c 1.1, CHCl3); 1H NMR
(CDCl3): l 8.09–7.40 (m, 10 H, PhH), 5.85 (m, 1 H,
CH2ꢀCH-CH2-), 5.33–5.13 (m, 2 H, CH2ꢀCH-CH2-),
5.22–5.15 (m, 1 H, H-4), 5.17 (d, 1 H, H-1) 5.06 (dd, 1
H, J1,2 3.7 Hz, H-2), 4.46 (dd, 1 H, J2,3=J3,4 9.6 Hz,
H-3), 4.25–3.98 (m, 2 H, CH2ꢀCH-CH2-), 3.95 (dd, 1
H, J4,5 5.8 Hz, H-5), 3.77 (dd, 1 H, J4,5%=J5,5% 10.8 Hz,
H-5%), 2.60 (br, 1 H, OH). Anal. Calcd for C22H22O7: C,
66.33; H, 5.53. Found: C, 66.10; H, 5.60.
1
foamy solid: H NMR (CDCl3): l 8.04–7.43 (m, 5 H,
PhH), 5.83 (m, 1 H, CH2ꢀCH-CH2-), 5.74 (dd, 1 H,
J2,3=J3,4 9.9 Hz, H-3), 5.30–5.11 (m, 2 H, CH2ꢀCH-
CH2-), 5.21 (d, 1 H, J1,2 3.6 Hz, H-1), 5.07 (m, 1 H,
H-4), 5.04 (dd, 1 H, H-2), 4.23–3.97 (m, 2 H, CH2ꢀCH-
CH2-), 3.87 (dd, 1 H, J4,5 6.0 Hz, H-5), 3.71 (dd, 1 H,
J4,5%=J5,5% 10.8 Hz, H-5%), 2.06 (s, 3 H, Ac), 1.97 (s, 3 H,
Ac). Anal. Calcd for C15H18O6: C, 47.62; H, 4.76.
Found: C, 47.48; H, 4.87.
2,3,4-Tri-O-benzoyl-h-
imidate (7) and 2,3,4-tri-O-benzoyl-i-
D
-xylopyranosyl trichloroacet-
D-xylopyranosyl
trichloroacetimidate (8).—To a solution of 4 (5.02 g,
10.0 mmol) in anhyd CH3OH (100 mL) was added
PdCl2 (0.5 g), and the mixture was stirred at 40 °C for
4 h, at the end of which time TLC (3:1 petroleum
ether–EtOAc) indicated that the reaction was complete.
The mixture was filtered, and the filtrate was concen-
trated to dryness. To the residue were added CCl3CN
(4.2 mL, 20 mmol), anhyd K2CO3 (5.00 g), and dry
CH2Cl2 (70 mL). The mixture was stirred overnight and
was then filtered, and the filtrate was concentrated in
vacuo. The residue was purified by flash chromatogra-
phy (3:1 petroleum ether–EtOAc) to give a mixture
(7:8=3:17) as a foamy solid (4.85 g, 80%): [h]D −18.6°
Allyl 2,3,4-tri-O-benzoyl-h-
2,3-di-O-benzoyl-h- -xylopyranoside (5) and allyl 2,4-
di-O-benzoyl-h- -xylopyranoside (6).—To a solution of
D-xylopyranoside (4), allyl
D
D
1 (3.80 g, 20.0 mmol) in pyridine (12 mL) was added
benzoyl chloride (5.0 mL, 43.1 mmol). The reaction
mixture was stirred overnight at rt. TLC (3:1 petroleum
ether–EtOAc) indicated that the reaction was complete.
Water (50 mL) was added, and the mixture was ex-
tracted with CH2Cl2 (3×50 mL). The extract was
washed with M HCl and satd aq NaHCO3, dried
(Na2SO4) and concentrated. Purification by flash chro-
matography (3:1 petroleum ether–EtOAc) gave 4 (2.51
g, 25%), and 5 (1.59 g, 20%), 6 (3.58 g, 45%) as a foamy
solid, respectively.
1
(c 1.1, CHCl3); H NMR (CDCl3): l 8.80 (s, 0.85 H,
NH (8)), 8.62 (s, 0.15 H, NH (7)), 8.16–7.32 (m, 15 H,
PhH), 6.73 (d, 0.15 H, J1,2 3.6 Hz, H-1 (7)), 6.44 (d,
0.85 H, J1,2 2.6 Hz, H-1 (8)), 6.25 (dd, 0.15 H, J2,3=J3,4
10.0 Hz, H-3 (7)), 5.72 (dd, 0.85 H, J2,3=J3,4 4.2 Hz,
H-3 (8)), 5.56 (dd, 0.15 H, H-2 (7)), 5.51 (dd, 0.85 H,
H-2 (8)), 5.51 (m, 0.15 H, H-4 (7)), 5.30 (m, 0.85 H,
H-4 (8)), 4.61 (dd, 0.85 H, J4,5 2.6 Hz, H-5 (8)), 4.30
(dd, 0.15 H, J4,5 5.8 Hz, J5,5% 11.2 Hz, H-5 (7)), 4.08 (dd,
0.85, 1 H, J4,5% 3.5 Hz, J5,5% 13.0 Hz, H-5% (8)), 4.08 (m,
0.15 H, H-5% (7)). Anal. Calcd for C28H22Cl3NO8: C,
55.40; H, 3.63. Found: C, 55.22; H, 3.64.
Or, to a solution of 2 (2.94 g, 10.0 mmol) in pyridine
(8 mL) was added benzoyl chloride (1.3 mL, 11.2
mmol). The reaction mixture was stirred overnight at
rt. TLC (3:1 petroleum ether–EtOAc) indicated that
the reaction was complete. Water (50 mL) was added,
and the mixture was extracted with CH2Cl2 (3×50
mL). The extract was washed with M HCl and satd aq
NaHCO3, dried (Na2SO4) and concentrated. Purifica-
tion by flash chromatography (3:1 petroleum ether–
EtOAc) gave 4 (1.20 g, 24%), and 5 (0.76 g, 19%), 6
(1.79 g, 45%) as a foamy solid, respectively; 4: [h]D
Allyl 2,4-di-O-benzoyl-3-O-chloroacetyl-h-D-xylopy-
ranoside (9).—To a solution of 6 (6.04 g, 15.2 mmol) in
1:3 pyridine–CH2Cl2 (40 mL) was added chloroacetyl
chloride (2.6 mL, 32.7 mmol). The reaction mixture was
stirred overnight at rt. TLC (3:1 petroleum ether–
EtOAc) indicated that the reaction was complete. Wa-
ter (100 mL) was added, and the mixture was extracted
with CH2Cl2 (3×100 mL). The extract was washed
with M HCl and satd aq NaHCO3, dried (Na2SO4) and
concentrated. Purification by flash chromatography (3:1
petroleum ether–EtOAc) gave 9 as a foamy solid (6.92
1
+65.1° (c 1.1, CHCl3); H NMR (CDCl3): l 8.00–7.31
(m, 15 H, PhH), 6.18 (dd, 1 H, J2,3=J3,4 9.6 Hz, H-3),
5.86 (m, 1 H, CH2ꢀCH-CH2-), 5.41 (m, 1 H, H-4),
5.34–5.14 (m, 2 H, CH2ꢀCH-CH2-), 5.30–5.26 (m, 2 H,
H-1, H-2), 4.29–4.03 (m, 2 H, CH2ꢀCH-CH2-), 4.11–
4.07 (dd, 1 H, J4,5 5.9 Hz, H-5), 3.89 (dd, 1 H, J4,5%
=
J5,5% 10.8 Hz, H-5%). Anal. Calcd for C29H26O8: C, 69.32;
H, 5.18. Found: C, 69.51; H, 5.15. 5: [h]D +141.1° (c
1
1
g, 96%): [h]D −0.3° (c 1.0, CHCl3); H NMR (CDCl3):
1.1, CHCl3); H NMR (CDCl3): l 8.00–7.35 (m, 10 H,
l 8.05–7.44 (m, 10 H, PhH), 5.99 (dd, 1 H, J2,3=J3,4
9.9 Hz, H-3), 5.83 (m, 1 H, CH2ꢀCH-CH2-), 5.32–5.13
(m, 2 H, CH2ꢀCH-CH2-), 5.32–5.27 (m, 2 H, H-4,
H-1), 5.17–5.13 (dd, 1 H, H-2), 4.27–4.01 (m, 2 H,
CH2ꢀCH-CH2-), 4.09–4.04 (dd, 1 H, J4,5 4.5 Hz, H-5),
3.91 (s, 2 H, ClCH2CO), 3.82 (t, 1 H, J4,5%=J5,5% 10.8
PhH), 5.84 (m, 1 H, CH2ꢀCH-CH2-), 5.66 (dd, 1 H,
J
2,3=J3,4 9.8 Hz, H-3), 5.34–5.14 (m, 2 H, CH2ꢀCH-
CH2-), 5.26 (dd, 1 H, H-2), 5.19 (d, 1 H, J1,2 3.7 Hz,
H-1), 4.28–4.00 (m, 2 H, CH2ꢀCH-CH2-), 4.04 (m, 1 H,
H-4), 3.87 (dd, 1 H, J4,5 5.8 Hz, H-5), 3.78 (dd, 1 H,
J4,5%=J5,5% 11.0 Hz, H-5%), 2.73 (br, 1 H, OH). Anal.

L. Chen, F. Kong / Carbohydrate Research 337 (2002) 2335–2341
2339
Hz, H-5%). Anal. Calcd for C24H23ClO8: C, 60.70; H,
4.85. Found: C, 60.95; H, 4.83.
(CH2ꢀCH-CH2-), 99.82, 95.11 (C-1), 75.22, 73.70,
70.15, 69.37, 68.63, 68.59, 68.36, 60.25, 58.92, JC-1–H-1
166.8 Hz (C-1II, b), JC-1–H-1 173.2 Hz (C-1I, a). Anal.
Calcd for C48H42O14: C, 68.41; H, 4.99. Found: C,
68.17; H, 5.04.
2,4-Di-O-benzoyl-3-O-chloroacetyl-h-
trichloroacetimidate (10) and 2,4-di-O-benzoyl-3-O-
chloroacetyl-i- -xylopyranosyl trichloroacetimidate
D-xylopyranosyl
D
(11).—To a solution of 9 (5.51 g, 11.6 mmol) in anhyd
CH3OH (100 mL) was added PdCl2 (0.5 g), and the
mixture was stirred at 40 °C for 4 h, at the end of which
time TLC (3:1 petroleum ether–EtOAc) indicated that
the reaction was complete. The mixture was filtered,
and the filtrate was concentrated to dryness. To the
residual solid were added CCl3CN (4.2 mL, 20 mmol),
anhyd K2CO3 (5.10 g), and dry CH2Cl2 (80 mL). The
mixture was stirred overnight and was then filtered, and
the filtrate was concentrated in vacuo. The residue was
purified by flash chromatography (3:1 petroleum ether–
EtOAc) to give a mixture (10:11=1:3) as a foamy solid
Allyl 2,4-di-O-benzoyl-3-O-chloroacetyl-i-
D-xylopy-
ranosyl-(1“3)-2,4-di-O-benzoyl-h- -xylopyranoside
D
(13).—The mixture of 10 and 11 (2.35 g, 4.1 mmol) and
acceptor 6 (1.64 g, 4.1 mmol) were dried together under
high vacuum for 2 h, then dissolved in anhyd CH2Cl2
(60 mL). TMSOTf (90 mL, 0.11 equiv) was added
dropwise at −25 °C with N2 protection. The reaction
mixture was stirred for 3 h, during which time the
mixture was gradually warmed to ambient temperature.
Then the mixture was neutralized with Et3N, concen-
trated and purified by flash chromatography (3:1
petroleum ether–EtOAc) to afford 13 as a foamy solid
1
(5.33 g, 80%): [h]D −12.9° (c 1.1, CHCl3); H NMR
1
(2.84 g, 85%): [h]D −1.6° (c 1.0, CHCl3); H NMR
(CDCl3): l 8.76 (s, 0.75 H, NH (11)), 8.61 (s, 0.25 H,
NH (10)), 8.05–7.32 (m, 10 H, PhH), 6.69 (d, 0.25 H,
J1,2 3.6 Hz, H-1 (10)), 6.28 (d, 0.75 H, J1,2 3.9 Hz, H-1
(11)), 6.03 (dd, 0.25 H, J2,3=J3,4 10.0 Hz, H-3 (10)),
5.58 (dd, 0.75 H, J2,3=J3,4 5.5 Hz, H-3 (11)), 5.46–5.37
(m, 1 H, H-2), 5.30–5.22 (m, 1 H, H-4), 4.51 (dd, 0.75
H, J4,5 3.4 Hz, J5,5% 12.7 Hz, H-5 (11)), 4.27 (dd, 0.25 H,
J4,5 5.9 Hz, J5,5% 11.2 Hz, H-5 (10)), 4.10 (s, 1.5 H,
ClCH2CO (11)), 3.99 (m, 1 H, H-5), 3.93 (s, 0.5 H,
ClCH2CO (10)). Anal. Calcd for C23H14Cl4NO8: C,
48.08; H, 2.44. Found: C, 48.28; H, 2.43.
(CDCl3): l 8.12–7.15 (m, 20 H, PhH), 5.76 (m, 1 H,
CH2ꢀCH-CH2-), 5.39 (dd, 1 H, J2,3=J3,4 6.9 Hz, H-
3II), 5.30 (m, 1 H, H-4I), 5.27–5.07 (m, 2 H, CH2ꢀCH-
CH2-), 5.12–5.07 (m, 4 H, H-1I, H-1II, H-2II, H-2I),
4.96 (m, 1 H, H-4II), 4.59 (dd, 1 H, J2,3=J3,4 8.9 Hz,
H-3I), 4.20–3.91 (m, 2 H, CH2ꢀCH-CH2-), 4.15 (dd, 1
H, H-5II), 3.98 (dd, 1 H, J4,5 5.8 Hz, J5,5% 10.8 Hz, H-5),
3.91 (d, 2 H, ClCH2CO), 3.78 (dd, 1 H, J4,5%=J5,5% 10.8
Hz, H-5%), 3.48 (dd, 1 H, J4,5 6.3 Hz, J5,5 10.8 Hz,
H-5II%); 13C NMR (CDCl3): l 166.35 (ClCH2CO),
165.47, 165.27, 165.24, 164.56 (PhCO), 133.46, 133.37,
133.23, 133.06, 129.74, 129.70, 129.58, 129.51, 129.47,
129.39, 129.01, 128.86, 128.40, 128.26, 128.10, 127.96,
117.71 (CH2ꢀCH-CH2-), 100.06, 95.08 (C-1), 75.44,
75.21, 73.40, 71.08, 69.86, 69.66, 68.63, 68.57, 60.75,
60.32, 40.27 (ClCH2CO), JC-1–H-1 172.7 Hz (C-1I, a),
JC-1–H-1 168.5 Hz (C-1II, b). Anal. Calcd for
C43H39ClO14: C, 63.35; H, 4.79. Found: C, 63.11; H,
4.81.
Allyl 2,3,4-tri-O-benzoyl-i-D-xylopyranosyl-(1“3)-
2,4-di-O-benzoyl-h- -xylopyranoside (12).—The mix-
D
ture of 7 and 8 (2.18 g, 3.6 mmol) and acceptor 6 (1.44
g, 3.6 mmol) were dried together under high vacuum
for 2 h, then dissolved in anhyd CH2Cl2 (60 mL).
TMSOTf (90 mL, 0.13 equiv) was added dropwise at
−25 °C with N2 protection. The reaction mixture was
stirred for 3 h, during which time the mixture was
gradually warmed to ambient temperature. The mixture
was then neutralized with Et3N, concentrated and
purified by flash chromatography (3:1 petroleum ether–
EtOAc) to afford 12 as a foamy solid (2.58 g, 85%):
2,3,4-Tri-O-benzoyl-i-
di-O-benzoyl-h- -xylopyranosyl
(14) and 2,3,4-tri-O-benzoyl-i-
2,4-di-O-benzoyl-i-
D
-xylopyranosyl-(1“3)-2,4-
D
trichloroacetimidate
-xylopyranosyl-(1“3)-
D
1
D-xylopyranosyl
trichloroacetimi-
[h]D −1.7° (c 1.1, CHCl3); H NMR (CDCl3): l 8.13–
date (15).—To a solution of 12 (3.14 g, 3.7 mmol) in
anhyd 2:1 CH3OH–CH2Cl2 (75 mL) was added PdCl2
(0.3 g), and the mixture was stirred at 40 °C for 4 h, at
the end of which time TLC (2:1 petroleum ether–
EtOAc) indicated that the reaction was complete. The
mixture was filtered, and the filtrate was concentrated
to dryness. To the residual solid were added CCl3CN
(1.4 mL, 6.7 mmol), anhyd K2CO3 (3.00 g), and dry
CH2Cl2 (40 mL). The mixture was stirred overnight and
was then filtered, and the filtrate was concentrated in
vacuo. The residue was purified by flash chromatogra-
phy (3:1 petroleum ether–EtOAc) to give a mixture
(14:15=47:53) as a foamy solid (2.80 g, 80%): [h]D
7.13 (m, 25 H, PhH), 5.77 (m, 1 H, CH2ꢀCH-CH2-),
5.55 (dd, 1 H, J2,3=J3,4 6.0 Hz, H-3II), 5.32 (m, 1 H,
H-4), 5.27–5.09 (m, 2 H, CH2ꢀCH-CH2-), 5.25 (d, 1 H,
H-1II), 5.17 (dd, J1,2 4.1 Hz, J2,3 6.0 Hz, H-2II), 5.14 (d,
1 H, J1,2 3.6 Hz, H-1I), 5.12–5.09 (m, 1 H, H-2), 5.03
(m, 1 H, H-4II), 4.66 (dd, 1 H, J2,3=J3,4 9.2 Hz, H-3I),
4.28 (dd, 1 H, J 3.5 Hz, J 12.6 Hz, H-5II), 4.21–3.92
(m, 2 H, CH2ꢀCH-CH2-), 4.02 (dd, 1 H, J4,5 5.9 Hz,
J5,5% 10.8 Hz, H-5I), 3.79 (dd, 1 H, J4,5%=J5,5% 10.7 Hz,
H-5I%), 3.58 (dd, 1 H, J4,5% 5.2 Hz, J5,5% 12.6 Hz, H-5II%);
13C NMR (CDCl3): l 165.54, 165.31, 165.31, 164.94,
164.50 (PhCO), 133.40, 133.34, 133.25, 133.11, 132.89,
129.76, 129.71, 129.56, 129.41, 129.16, 129.09, 128.82,
128.70, 128.40, 128.32, 128.26, 127.96, 117.66
1
−31.2° (c 1.1, CHCl3); H NMR (CDCl3): l 8.63 (s,

2340
L. Chen, F. Kong / Carbohydrate Research 337 (2002) 2335–2341
0.53 H, NH (15)), 8.54 (s, 0.47 H, NH (14)), 6.56 (d,
0.47 H, J1,2 3.6 Hz, H-1 (14)), 6.32 (s, 0.53 H, H-1 (15)),
5.45 (m, 0.47 H, H-4 (14)), 4.71 (dd, 0.47 H, J2,3=J3,4
9.4 Hz, H-3 (14)), 4.22 (dd, 0.47 H, H-5 (14)). Anal.
Calcd for C47H38Cl3NO14: C, 59.59; H, 4.01. Found: C,
59.79; H, 4.07.
129.38, 129.15, 129.12, 128.99, 128.85, 128.60, 128.60,
128.36, 128.30, 128.24, 128.21, 128.17, 128.14, 128.05,
127.92, 117.92, 117.41 (CH2ꢀCH-CH2-), 100.29, 98.74,
98.60, 94.93 (C-1), 75.66, 73.33, 72.67, 70.10, 69.94,
69.69, 69.56, 69.47, 69.36, 69.04, 68.87, 68.80, 68.45,
60.81, 60.42, 60.42, 60.02, 58.83. Anal. Calcd for
C86H74O26: C, 67.81; H, 4.86. Found: C, 67.55; H, 4.88.
Allyl
2,4-di-O-benzoyl-i-
D-xylopyranosyl-(1“3)-
2,4-di-O-benzoyl-h-
D
-xylopyranoside (16).—To a solu-
2,3,4-Tri-O-benzoyl-i-
di-O-benzoyl-i- -xylopyranosyl-(1“3)-2,4-di-O-ben-
zoyl-i- -xylopyranosyl-(1“3)-2,4-di-O-benzoyl-h-
xylopyranosyl trichloroacetimidate (18) and 2,3,4-tri-O-
benzoyl-i- -xylopyranosyl-(1“3)-2,4-di-O-benzoyl-
i- -xylopyranosyl-(1“3)-2,4-di-O-benzoyl-i- -xylo-
pyranosyl-(1“3)-2,4-di-O-benzoyl-i- -xylopyranosyl
D
-xylopyranosyl-(1“3)-2,4-
tion of 13 (3.04 g, 3.7 mmol) in 1:4 EtOH–CH2Cl2 (125
mL) was added thiourea (0.36 g), and the mixture was
refluxed for 16 h, at the end of which time TLC (3:1
petroleum ether–EtOAc) indicated that the reaction
was complete. The mixture was concentrated. The
residue was passed through a silica-gel column with 3:1
petroleum ether–EtOAc as the eluent to give 16 as a
foamy solid (2.18 g, 80%): [h]D −2.3° (c 0.9, CHCl3);
1H NMR (CDCl3): l 8.12–7.19 (m, 20 H, PhH), 5.78
(m, 1 H, CH2ꢀCH-CH2-), 5.32 (m, 1 H, H-4I), 5.29–
5.11 (m, 5 H, CH2ꢀCH-CH2-, H-1II, H-1I, H-2II), 4.91
(dd, 1 H, J1,2 3.8 Hz, J2,3 5.3 Hz, H-2II), 4.86 (m, 1 H,
H-4II), 4.63 (dd, 1 H, J2,3=J3,4 9.2 Hz, H-3I), 4.23–3.95
(m, 5 H, CH2ꢀCH-CH2-, H-5II, H-5I, H-3II), 3.80 (dd, 1
H, J4,5=J5,5 10.7 Hz, H-5), 3.50 (dd, 1 H, J4,5 4.2 Hz,
J5,5%12.8 Hz, H-5II), 2.90 (br, 1 H, OH). Anal. Calcd for
C41H38O13: C, 66.67; H, 5.15. Found: C, 66.45; H, 5.17.
D
D
D-
D
D
D
D
trichloroacetimidate (19).—To a solution of 17 (1.38 g,
0.91 mmol) in anhyd 1:1 CH3OH–CH2Cl2 (50 mL) was
added PdCl2 (0.1 g), and the mixture was stirred at
40 °C for 4 h, at the end of which time TLC (2:1
petroleum ether–EtOAc) indicated that the reaction
was complete. The mixture was filtered, and the filtrate
was concentrated to dryness. To the residual solid were
added CCl3CN (0.7 mL, 3.3 mmol), anhyd K2CO3 (1.30
g), and dry CH2Cl2 (30 mL). The mixture was stirred
overnight and was then filtered, and the filtrate was
concentrated in vacuo. The residue was purified by
flash chromatography (2:1 petroleum ether–EtOAc) to
give a mixture (18:19=1:1) as a foamy solid (1.18 g,
Allyl 2,3,4-tri-O-benzoyl-i-
2,4-di-O-benzoyl-i- -xylopyranosyl-(1“3)-2,4-di-O-
benzoyl-i- -xylopyranosyl-(1“3)-2,4-di-O-benzoyl-h-
-xylopyranoside (17).—The mixture of 14 and 15 (1.51
D-xylopyranosyl-(1“3)-
D
1
D
80%): [h]D −23.9° (c 1.1, CHCl3); H NMR (CDCl3):
D
l 8.56 (s, 1 H, NH (19)), 8.50 (s, 1 H, NH (18)), 6.36 (d,
1 H, J1,2 3.6 Hz, H-1 (18)), 6.14 (d, 1 H, J1,2 3.5 Hz,
H-1 (19)). Anal. Calcd for C85H70Cl3NO26: C, 62.71; H,
4.30. Found: C, 62.94; H, 4.28.
g, 1.6 mmol) and acceptor 16 (1.18 g, 1.6 mmol) were
dried together under high vacuum for 2 h, then dis-
solved in anhyd CH2Cl2 (20 mL). TMSOTf (45 mL, 0.15
equiv) was added dropwise at −25 °C with N2 protec-
tion. The reaction mixture was stirred for 3 h, during
which time the mixture was gradually warmed to ambi-
ent temperature. Then the mixture was neutralized with
Et3N, concentrated and purified by flash chromatogra-
phy (2:1 petroleum ether–EtOAc) to afford 17 as a
foamy solid (1.95 g, 80%): [h]D −7.3° (c 1.1, CHCl3);
1H NMR (CDCl3): l 8.08–6.98 (m, 45 H, PhH), 5.73
(m, 1 H, CH2ꢀCH-CH2-), 5.65 (dd, 1 H, J2,3=J3,4 6.8
Hz, H-3IV), 5.26 (dd, 1 H, H-2IV), 5.21–5.04 (m, 2 H,
CH2ꢀCH-CH2-), 5.14 (m, 1 H, H-4IV), 5.11 (d, 1 H, J1,2
3.9 Hz, H-1III), 5.01 (d, 1 H, J1,2 4.8 Hz, H-1IV), 5.00
(m, 2 H, H-2III, H-4III), 4.99 (d, 1 H, H-1I), 4.90 (m, 1
H, H-4I), 4.84 (d, 1 H, J1,2 4.3 Hz, H-1II), 4.79 (dd, 1 H,
J1,2 4.3 Hz, J2,3 6.3 Hz, H-2II), 4.73 (dd, 1 H, J1,2 3.6
Hz, H-2I), 4.66 (m, 1 H, H-4II), 4.39 (dd, 1 H, J2,3=J3,4
9.3 Hz, H-3I), 4.27 (dd, 1 H, J4,5 3.9 Hz, J5,5 12.3 Hz,
H-5), 4.23 (dd, 1 H, J2,3=J3,4 5.7 Hz, H-3III), 4.13–3.87
(m, 2 H, CH2ꢀCH-CH2-), 4.13–4.05 (m, 2 H), 3.93–
3.87 (m, 2 H), 3.64–3.57 (m, 2 H, H-5, H-5), 3.34–3.28
(m, 2 H); 13C NMR (CDCl3): l 165.34, 165.27, 165.22,
165.11, 165.03, 164.99, 164.48, 164.22, 164.15 (PhCO),
133.30, 133.27, 133.16, 133.07, 133.02, 132.95, 132.70,
129.86, 129.78, 129.75, 129.71, 129.66, 129.53, 129.48,
Allyl i-D-xylopyranosyl-(1“3)-i-D-xylopyranosyl-
(1“3)-i-
D
-xylopyranosyl-(1“3)-h-
D-xylopyranoside
(20).—Compound 17 (0.15 g, 0.10 mmol) was dissolved
in a satd solution of NH3 in anhyd CH3OH (20 mL).
After one week at rt, the reaction mixture was concen-
trated, and the residue was purified by chromatography
on Sephadex LH-20 (MeOH) to afford 20 as a syrup
1
(53 mg, 90%): [h]D +2.8° (c 1.0, CHCl3); H NMR
(D2O): l 5.88 (m, 1 H, CH2ꢀCH-CH2-), 5.29–5.16 (m,
2 H, CH2ꢀCH-CH2-), 4.83 (d, 1 H, J1,2 3.6 Hz, H-1I),
4.60 (d, 1 H, J1,2 8.0 Hz, H-1IV), 4.57 (d, 1 H, J1,2 8.0
Hz, H-1III), 4.55 (d, 1 H, J1,2 8.4 Hz, H-1II), 4.16–3.94
(m, 2 H, CH2ꢀCH-CH2-), 3.92–3.85 (m, 3 H), 3.75–
3.70 (m, 1 H), 3.64–3.34 (m, 11 H), 3.25–3.18 (m, 4 H);
13C NMR (D2O): l 135.82 (CH2ꢀCH-CH2-), 120.66
(CH2ꢀCH-CH2-), 105.81, 105.64, 105.55, 99.70 (C-1),
II,
86.01, 85.96, 84.18 (C-3III,
I), 77.98, 75.74, 75.48,
75.43, 73.20, 71.57, 70.91, 70.12, 70.05, 70.05, 67.53,
67.18, 67.18, 63.49. MALDI TOFMS Calcd for
C23H38O17: [M] 586.2, Found: [M+Na] 609.0.
Allyl 2,3,4-tri-O-benzoyl-i-
2,4-di-O-benzoyl-i- -xylopyranosyl-(1“3)-2,4-di-O-
benzoyl-i- -xylopyranosyl-(1“3)-2,4-di-O-benzoyl-
i- -xylopyranosyl-(1“3)-2,4-di-O-benzoyl-i- -xylo-
D-xylopyranosyl-(1“3)-
D
D
D
D

L. Chen, F. Kong / Carbohydrate Research 337 (2002) 2335–2341
2341
pyranosyl-(1“3)-2,4-di-O-benzoyl-h-
D
-xylopyranoside
on Sephadex LH-20 (MeOH) to afford 22 as a syrup
(87 mg, 85%): [h]D +1.6° (c 1.1, CHCl3); H NMR
1
(21).—The mixture of 18 and 19 (0.55 g, 0.34 mmol)
and acceptor 16 (0.25 g, 0.34 mmol) were dried together
under high vacuum for 2 h, then dissolved in anhyd
CH2Cl2 (20 mL). TMSOTf (15 mL, 0.23 equiv) was
added dropwise at −25 °C with N2 protection. The
reaction mixture was stirred for 3 h, during which time
the mixture was gradually warmed to ambient tempera-
ture. Then the mixture was neutralized with Et3N,
concentrated and purified by flash chromatography
(1.5:1 petroleum ether–EtOAc) to afford 21 as a foamy
solid (0.56 g, 75%): [h]D −1.1° (c 1.1, CHCl3); 1H
NMR (CDCl3): l 8.10–6.92 (m, 65 H, PhH), 5.70 (m,
1 H, CH2ꢀCH-CH2-), 5.65 (dd, 1 H, J2,3=J3,4 7.0 Hz,
H-3VI), 5.26 (dd, 1 H, J1,2 5.3 Hz, J2,3 7.0 Hz, H-2VI),
5.19–5.03 (m, 2 H, CH2ꢀCH-CH2-), 5.15–5.03 (m, 4
H), 5.00 (m, 1 H, H-4V), 4.95 (m, 3 H), 4.88 (m, 1 H,
H-4IV), 4.78 (d, 1 H, J1,2 4.8 Hz, H-1IV), 4.72–4.62 (m,
5 H), 4.52 (m, 2 H), 4.38–4.23 (m, 3 H), 4.15–4.06 (m,
3 H), 4.09–3.82 (m, 2 H, CH2ꢀCH-CH2-), 3.98–3.77
(m, 5 H), 3.63–3.57 (m, 2 H), 3.42 (dd, 1 H, J4,5 5.3 Hz,
J5,5% 12.7 Hz, H-5), 3.27 (dd, 1 H, J4,5 4.5 Hz, J5,5% 12.6
Hz, H-5), 3.21–3.10 (m, 2 H); 13C NMR (CDCl3): l
165.34, 165.28, 165.28, 165.03. 165.03, 165.03, 164.99,
164.99, 164.50, 164.24, 164.19, 164.05, 164.05 (PhCO),
133.34, 133.25, 133.17, 133.12, 133.09, 133.06, 132.96,
132.86, 132.71, 129.91, 129.79, 129.75, 129.72, 129.68,
129.58, 129.49, 129.43, 129.28, 129.17, 129.03, 129.00,
128.84. 128.73, 128.52, 128.42, 128.28, 128.22, 128.19,
128.16, 128.11, 127.96, 117.46 (CH2ꢀCH-CH2-), 100.52,
98.95, 98.90, 99.69, 99.69, 94.88 (C-1), 77.17, 75.68,
73.29, 70.17, 70.00, 69.83, 69.70, 69.66, 69.54, 68.98,
68.46, 60.90, 60.64, 60.48, 60.29, 60.21, 58.76, JC-1–H-1
(D2O): l 5.88 (m, 1 H, CH2ꢀCH-CH2-), 5.29–5.16 (m,
2 H, CH2ꢀCH-CH2-), 4.83 (d, 1 H, J1,2 3.6 Hz, H-1I),
4.62–4.54 (m, 5 H, H-1VI, V, IV, III, II), 4.15–3.94 (m, 2
H, CH2ꢀCH-CH2-), 3.92–3.85 (m, 5 H), 3.75–3.33 (m,
19 H), 3.25–3.19 (m, 6 H); 13C NMR (D2O): l 135.82
(CH2ꢀCH-CH2-), 120.67 (CH2ꢀCH-CH2-), 105.82,
105.65, 105.57, 105.57, 105.57, 99.70 (C-1), 86.03, 85.99,
85.91, 85.91, 84.20 (C-3V, IV, III, II, I), 77.99, 75.74, 75.48,
75.43, 73.20, 71.57, 70.91, 70.15, 70.05, 67.53, 67.18,
63.49 MALDI TOFMS Calcd for C33H54O25: [M] 850.3,
Found: [M+Na] 873.0.
Acknowledgements
This work was supported by The Chinese Academy
of Sciences (KIP-RCEES9904) and by The National
Natural Science Foundation of China (Projects
39970864, and 30070815), and The Ministry of Science
and Technology.
References
1. Ito, M.; Yamaguchi, K.; Izumi, K. Jpn. Kokai Tokyo Koho
JP2001-86999; Chem. Abstr. 2001, 134, 247238w.
2. (a) Takeo, K.; Ohguchi, Y.; Hasegawa, R.; Kitamura, S.
Carbohydr. Res. 1995, 278, 301–313;
(b) Hirsch, J.; Kova´cˇ, P.; Petra´kova´, E. Carbohydr. Res.
1982, 106, 203–216;
(c) Takeo, K.; Murata, Y.; Kitamura, S. Carbohydr. Res.
1992, 224, 311–318;
(d) Takeo, K.; Ohguchi, Y.; Hasegawa, R.; Kitamura, S.
Carbohydr. Res. 1995, 277, 231–244.
174.8 Hz (C-1I, a), 167.6 Hz, 167.6 Hz, 165.8 Hz, 165.8
V, IV, III,
Hz, 161.6 Hz (C-1VI,
II, b). Anal. Calcd for
3. Dupeyre, D.; Excoffier, G.; Utille, J. P. Carbohydr. Res.
1984, 135, C1–C4.
4. (a) Helm, R. F.; Ralph, J.; Anderson, L. J. Org. Chem.
1991, 56, 7015–7021;
(b) Kondo, Y. Carbohydr. Res. 1982, 107, 303–311.
5. Fukase, K.; Hase, S.; Ikenaka, T.; Kusumoto, S. Bull.
Chem. Soc. Jpn. 1992, 65, 436–445.
6. Schmidt, R. R.; Kinzy, W. Ad6. Carbohydr. Chem.
Biochem. 1994, 50, 21–125.
C125H106O38: C, 67.75; H, 4.79. Found: C, 68.01; H,
4.77.
Allyl i-
D-xylopyranosyl-(1“3)-i-D-xylopyranosyl-
(1“3)-i-
(1“3)-i-
D
D
-xylopyranosyl-(1“3)-i-
-xylopyranosyl-(1“3)-h-
D
-xylopyranosyl-
-xylopyranoside
D
(22).—Compound 21 (0.26 g, 0.12 mmol) was dissolved
in a satd solution of NH3 in anhyd CH3OH (20 mL).
After one week at rt, the reaction mixture was concen-
trated, and the residue was purified by chromatography
7. Ogawa, T.; Yamamoto, H. Carbohydr. Res. 1985, 137,
79–88.