An efficient and practical synthesis of α-(1→3)-linked mannohexaose and mannooctaose

Article abstract of DOI:10.1081/CAR-120014899

α-(1→3)-Linked mannohexaose and mannooctaose as their methyl glycosides were synthesized from condensation of the corresponding α-(1→3)-linked di- (9) and tetrasaccharide donor (21) with the tetrasaccharide acceptor (23), respectively, followed by deacylation. The donor 21 and acceptor 23 were prepared readily from activation of C-1 of the tetrasaccharide 20 and deallylation of the tetrasaccharide 22, respectively. The tetrasaccharide 20 was prepared from oxidative cleavage of 1-O-p-methoxyphenyl of 19, which was obtained from coupling of 9 with 11. The tetrasaccharide 22 was obtained from condensation of the donor 13 with the acceptor 18. These disaccharides 9, 11, 13, and 18 were produced easily by simple chemical transformation using p-methoxyphenyl 3-O-allyl-α-D-mannopyranoside (1) and 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate (6), and methyl 3-O-allyl-α-D-mannopyranoside (14) as the synthons.

Full text of DOI:10.1081/CAR-120014899

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
AN EFFICIENT AND PRACTICAL SYNTHESIS
OF α-(1→3)-LINKED MANNOHEXAOSE AND
MANNOOCTAOSE
Langqiu Chen & Fanzuo Kong
To cite this article: Langqiu Chen & Fanzuo Kong (2002) AN EFFICIENT AND PRACTICAL
SYNTHESIS OF α-(1→3)-LINKED MANNOHEXAOSE AND MANNOOCTAOSE, Journal of
Carbohydrate Chemistry, 21:5, 341-353
To link to this article: http://dx.doi.org/10.1081/CAR-120014899
Published online: 21 Aug 2006.
Submit your article to this journal
Article views: 33
View related articles
Citing articles: 8 View citing articles
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lcar20
Download by: [University of Nebraska, Lincoln]
Date: 19 October 2015, At: 00:03

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 21, No. 5, pp. 341–353, 2002
AN EFFICIENT AND PRACTICAL SYNTHESIS
!
OF a-(1 3)-LINKED MANNOHEXAOSE
AND MANNOOCTAOSE
*
Langqiu Chen and Fanzuo Kong
Research Center for Eco-Environmental Science, Academia Sinica,
P.O. Box 2871, Beijing 100085, China
ABSTRACT
a-(1 !3)-Linked mannohexaose and mannooctaose as their methyl glyco-
sides were synthesized from condensation of the corresponding a-(1 !3)-
linked di- (9) and tetrasaccharide donor (21) with the tetrasaccharide acceptor
(23), respectively, followed by deacylation. The donor 21 and acceptor 23
were prepared readily from activation of C-1 of the tetrasaccharide 20 and
deallylation of the tetrasaccharide 22, respectively. The tetrasaccharide 20
was prepared from oxidative cleavage of 1-O-p-methoxyphenyl of 19, which
was obtained from coupling of 9 with 11. The tetrasaccharide 22 was
obtained from condensation of the donor 13 with the acceptor 18. These
disaccharides 9, 11, 13, and 18 were produced easily by simple chemical
transformation using p-methoxyphenyl 3-O-allyl-a-D-mannopyranoside (1)
and 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl trichloroacetimidate (6),
and methyl 3-O-allyl-a-D-mannopyranoside (14) as the synthons.
Key Words: Mannan; Trichloroacetimidate; Synthesis
*
Corresponding author. Fax: + 86-10-62923563; E-mail: fzkong@mail.rcess.ac.cn
341
DOI: 10.1081/CAR-120014899
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright D 2002 by Marcel Dekker, Inc.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
342
CHEN AND KONG
INTRODUCTION
a-(1! 3)-Linked mannans occur in the fruit body polysaccharide of Tremella
fuciformis and Dictyophora indusiata Fisch[1] and are the backbone of glucuronox-
ylomannan (GXM) antigens.[2] It was also reported that linear a-(1 ! 3)-linked mannan
reacts with L. ovata agglutinin.[3] Synthesis of a-(1 ! 3)-linked mannan is of interest
since it can afford a pure sample in enough quantity for structure–bioactivity relationship
studies. The synthesis of a-(1 !3)-linked mannohexaose has been achieved through a
Scheme 1. Reagents and conditions: (a) PhCOCl/Pyr, rt. (b) PdCl2, CH3OH, 40°C. (c) CAN,
CH3CN H2O, rt. (d) TMSOTf, CH2Cl2, ꢀ 25°C to rt. (e) CCl3CN, CH2Cl2, K2CO3, rt. (f) NH3/
CH3OH, rt.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
!
a-(1 3)-LINKED MANNOHEXAOSE AND MANNOOCTAOSE
343
stepwise strategy using 3-O-acetyl-2,4,6-tri-O-benzyl-a-D-mannopyranosyl chloride as
the donor and benzyl 2,4,6-tri-O-benzyl-a-D-mannopyranoside as the acceptor. This
synthesis involved rather complex procedures for the preparations of both the donor and
acceptor.[1] We provide herein a new method for the synthesis of a-(1 !3)-linked
mannohexaose and mannooctaose using an acyl temporary protective group.
RESULTS AND DISCUSSION
As outlined in Scheme 1, p-methoxyphenyl 3-O-allyl-a-D-mannopyranoside (1)
was chosen as the starting material, and obtained readily from allylation of p-
methoxyphenyl a-D-mannopyranoside through a dibutyltin complex under the same
conditions used for transformation of allyl a-D-mannopyranoside to allyl 3-O-allyl-a-D-
mannopyranoside.[4] Benzoylation of 1 with benzoyl chloride in pyridine quantitatively
gave 3-O-allyl-2,4,6-tri-O-benzoyl-a-D-mannopyranoside (2). Deallylation of 2 with
PdCl2 was carried out smoothly[5] giving the acceptor p-methoxyphenyl 2,4,6-tri-O-
benzoyl-a-D-mannopyranoside (3) in high yield (90%). Meanwhile, oxidative cleavage
of 1-O-p-methoxyphenyl of 2 with ammonium ceric nitrate (CAN), followed by
trichloroacetimidation[6] afforded the donor 3-O-allyl-2,4,6-tri-O-benzoyl-a-D-manno-
pyranosyl trichloroacetimidate (5) in satisfactory yield (72% for 2 steps). The acceptor
3 was coupled with 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl trichloroacetimidate
(6)[6] to give the disaccharide 7. Removal of the p-methoxyphenyl group of 7 with
CAN, followed by trichloroacetimidation with trichloroacetonitrile in the presence of
potassium carbonate afforded the nonreducing end disaccharide donor 9 (72% for 2
steps). Coupling of 3 with 5 afforded the disaccharide 10, and subsequent deallylation
furnished the disaccharide acceptor 11 (72% for 2 steps). Condensation of 9 with 11
gave the tetrasaccharide 19, and subsequent removal of p-methoxyphenyl, and
trichloroacetimidation yielded the tetrasaccharide donor 21. Transformation of 10 to
the disaccharide donor 13 was readily carried out by treatment of 10 with CAN,
followed by trichloroacetimidation. Coupling of 13 with the disaccharide acceptor 18,
which was obtained from coupling of methyl 2,4,6-tri-O-benzoyl-a-D-mannopyranoside
(16) with 5 followed by deallylation, gave the tetrasaccharide 22, and subsequent
deallylation afforded the tetrasaccharide acceptor 23. Condensation of 9 with 23 gave
the protected mannohexaose 24, while condensation of 21 with 23 gave the acylated
mannooctaose 26. Treatment of 24 and 26 with saturated ammonia–methanol afforded
methyl mannohexaoside 25 and mannooctaoside 27 respectively. JC1–H1 values (170–
172 Hz) were determined for 25 and 27, confirming the sole a-linkages in the
oligosaccharides.[7]
In summary, a facile and practical method was presented for the syntheses of a-
(1 ! 3)-linked mannose oligosaccharides.
EXPERIMENTAL
General methods. Optical rotations were determined at 25°C with a Perkin–
Elmer Model 241-MC automatic polarimeter. Melting points were determined with a
1
1
‘‘Mel-Temp’’ apparatus. H NMR, 13C NMR, and H NMR HOMO COSY spectra

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
344
CHEN AND KONG
were recorded with Bruker ARX 400 spectrometers for solutions in CDCl3 or D2O as
indicated. Chemical shifts are given in parts per million (ppm) downfield from internal
Me4Si. Mass spectra were recorded with a VG PLATFORM mass spectrometer using
the electrospray-ionization mode. Thin-layer chromatography (TLC) was performed on
Silica Gel HF254 with detection by charring with 30% (v/v) H2SO4 in MeOH or in
some cases by UV detection. Column chromatography was conducted by elution of a
column (16 ꢁ 240, 18ꢁ 300, 35 ꢁ 400 mm) of silica gel (100–200 mesh) with EtOAc–
petroleum ether (60–90°C) as the eluent. Solutions were concentrated at <60°C under
diminished pressure.
p-Methoxyphenyl 3-O-Allyl-2,4,6-tri-O-benzoyl-a-D-mannopyranoside (2). p-
Methoxyphenyl a-D-mannopyranoside[8] (5.00 g, 17.5 mmol) and Bu2SnO (4.80 g, 19.3
mmol) were added to CH3OH (200 mL), the mixture was heated under reflux for 2 h,
then concentrated to dryness. The residue was diluted with benzene (200 mL), and allyl
bromide (18.0 mL, 211 mmol), and Bu4NI (6.46 g, 17.5 mmol) were added to the
mixture. The reaction was carried out at 60°C for 24 h. TLC (3:1 EtOAc–CH3OH)
indicated that the reaction was complete. Concentration of the reaction mixture and
purification by flash chromatography (EtOAc) gave 1 as a syrup (3.70 g, 65%);
[a]D20 +95.4° (c 1.1, CHCl3); 1H NMR (CDCl3): d 6.98 (d, 2 H, J= 9.1 Hz, p-
CH3O PhH), 6.82 (d, 2 H, J=9.1 Hz, p-CH3O PhH), 6.00 (m, 1 H, CH2 CH
CH2 ), 5.51 (d, 1 H, J1,2 = 1.6 Hz, H-1), 5.40–5.25 (m, 2 H, CH2 CH CH2 ),
4.30–4.16 (m, 2 H, CH2 CH CH2 ), 4.21 (m, 1 H), 4.11 (dd, 1 H, J3,4 = J4,5
=
9.5 Hz, H-4), 3.91–3.87 (dd, 1 H, J5,6 =3.2 Hz, J6,6’ =12.3 Hz, H-6), 3.86–3.83 (dd, 1
H, J2,3 =3.2 Hz, J3,4 = 9.5 Hz, H-3), 3.78–3.73 (m, 2 H), 3.77 (s, 3 H, CH3), 2.98 (br, 3
H, OH). To a solution of 1 (6.52 g, 20.0 mmol) in pyridine (16 mL) was added benzoyl
chloride (8.34 mL, 72.0 mmol). After stirring the mixture overnight at rt, TLC (3:1
petroleum ether–EtOAc) indicated that the reaction was complete. Methanol (6 mL)
was added to the reaction mixture, and stirring was continued for 10 min. Water (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) quantitatively gave
1
2 as a foamy solid (12.76 g, 100%); [a]D +19.1° (c 1.0, CHCl3); H NMR (400 MHz,
CDCl3): d 8.12–7.38 (m, 15 H, PhH), 7.08 (d, 2 H, J =9.1 Hz, p-CH3O PhH), 6.76
(d, 2 H, J=9.1 Hz, p-CH3O PhH), 5.86 (t, 1 H, J3,4 =J4,5 =9.8 Hz, H-4), 5.79–5.69
(m, 2 H, H-2, CH2 CH CH2 ), 5.61 (d, 1 H, J1,2 =1.8 Hz, H-1), 5.23–5.06 (m, 2
H, CH2 CH CH2 ), 4.63–4.61 (m, 1 H), 4.45–4.42 (m, 2 H), 4.38–4.34 (dd, 1
H, J2,3 =3.3 Hz, J3,4 =9.8 Hz, H-3), 4.22–4.04 (m, 2 H, CH2 CH CH2 ), 3.73 (s,
3 H, CH3).
Anal. Calcd for C37H34O10: C, 69.59; H, 5.33. Found: C, 69.82; H, 5.31.
p-Methoxyphenyl 2,4,6-Tri-O-benzoyl-a-D-mannopyranoside (3). To a solu-
tion of 2 (1.28 g, 2.0 mmol) in anhyd CH3OH (50 mL) was added PdCl2 (0.1 g), and
the mixture was stirred at 40°C for 2–4 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. The residue was passed through a silica-gel
column with 2:1 petroleum ether–EtOAc as the eluent to give 3 as a syrup (1.08 g,
1
90%): [a]D +10.3° (c 1.0, CHCl3); H NMR (400 MHz, CDCl3): d 8.17–7.44 (m, 15 H,

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
!
a-(1 3)-LINKED MANNOHEXAOSE AND MANNOOCTAOSE
345
PhH), 7.14 (d, 2 H, J =8.8 Hz, p-CH3O PhH), 6.85 (d, 2 H, J= 8.8 Hz, p-CH3O
PhH), 5.81 (dd, 1 H, J3,4 =J4,5 =9.8 Hz, H-4), 5.72–5.69 (m, 2 H, H-1, H-2), 4.72–4.69
(m, 2 H, H-3, H-6), 4.56–4.51 (m, 2 H, H-5, H-6), 3.82 (s, 3 H, CH3O).
Anal. Calcd for C34H30O10: C, 68.23; H, 5.02. Found: C, 68.44; H, 5.00.
3-O-Allyl-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl trichloroacetimidate (5).
To a solution of 2 (12.76 g, 20.0 mmol) in 4:1 CH3CN H2O (900 mL) was added
CAN [(NH4)2Ce(NO3)6, 43.86 g, 80.0 mmol], and the mixture was stirred at rt for 30
min, at the end of which time TLC (3:1 petroleum ether–EtOAc) indicated that the
reaction was complete. The mixture was extracted with EtOAc, and washed with satd
aq NaHCO3. The organic layer was concentrated under reduced pressure, and purified
by column chromatography (3:1 petroleum ether–EtOAc) to afford 4 as a syrup (8.52
g, 80%). To a solution of 4 (4.50 g, 8.5 mmol) in CH2Cl2 (40 mL) were added
trichloroacetonitrile (2.5 mL) and anhyd potassium carbonate (4.50 g). The reaction
mixture was stirred overnight at rt and then filtered, and the filtrate was concentrated in
vacuo. The residue was purified by flash chromatography (3:1 petroleum ether–EtOAc)
1
to give 5 (5.15 g, 90%) as a syrup; [a]D ꢀ 8.9° (c 1.0, CHCl3); H NMR (400 MHz,
CDCl3): d 8.81 (s, NH ), 8.11–7.27 (m, 15 H, PhH), 6.49 (d, 1 H, J1,2 = 1.6 Hz, H-1),
5.95 (dd, 1 H, J3,4 =J4,5 =9.8 Hz, H-4), 5.79 (dd, 1 H, J1,2 =1.6 Hz, J2,3 =3.3 Hz, H-2),
5.70 (m, 1 H, CH2 CH CH2 ), 5.26–5.08 (m, 2 H, CH2 CH CH2 ), 4.70–4.67
(dd, 1 H, J= 1.6 Hz, J=11.7 Hz, H-6), 4.47–4.40 (m, 2 H, H-5, H-6), 4.27–4.24 (dd, 1
H, J2,3 = 3.3 Hz, J3,4 =9.8 Hz, H-3), 4.18–4.01 (m, 2 H, CH2 CH CH2 ).
Anal. Calcd for C32H28Cl3NO9: C, 56.76; H, 4.14. Found: C, 56.60; H, 4.15.
!
p-Methoxyphenyl 2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-
tri-O-benzoyl-a-D-mannopyranoside (7). 2,3,4,6-Tetra-O-benzoyl-a-D-mannopyra-
nosyl trichloroacetimidate[5] (6, 1.48 g, 2.0 mmol) and p-methoxyphenyl 2,4,6-tri-O-
benzoyl-a-D-mannopyranoside (3, 1.20 g, 2.0 mmol) were dried together under high
vacuum for 2 h, then dissolved in anhydrous CH2Cl2 (20 mL). TMSOTf (30 mL, 0.08
equiv) was added dropwise at ꢀ 25°C with N2 protection. The reaction mixture was
stirred for 3 h, during which time the temperature was gradually warmed to ambient
temperature. Then the mixture was neutralized with triethylamine, concentrated and
purified by flash chromatography (2:1 petroleum ether–EtOAc) to afford 7 as a foamy
1
solid (2.00 g, 85%); [a]D ꢀ 42.6° (c 1.0, CHCl3); H NMR (400 MHz, CDCl3): d 8.24–
7.21 (m, 35 H, PhH), 7.02 (d, 1 H, J=9.1 Hz, p-CH3O PhH), 6.75 (d, 1 H, J=9.1 Hz,
p-CH3O PhH), 6.05 (dd, 1 H, J3,4 =J4,5 = 9.9 Hz, H-4II), 6.01 (dd, 1 H, J3,4 = J4,5 =9.9
Hz, H-4I), 5.87 (dd, 1 H, J1,2 = 1.8 Hz, J2,3 = 3.3 Hz, H-2II), 5.72 (dd, 1 H, H-3II), 5.69
(d, 1 H, H-1II), 5.42 (d, 1 H, H-1I), 5.36 (dd, 1 H, J1,2 = 1.7 Hz, J2,3 = 3.2 Hz, H-2I), 4.84
(dd, 1 H, H-3I), 4.65–4.58 (m, 2 H), 4.54–4.45 (m, 3 H), 4.36 (dd, 1 H, J5,6 = 3.9 Hz,
J
6,6 = 12.3 Hz, H-6), 3.74 (s, 1 H, CH3O).
Anal. Calcd for C68H56O19: C, 69.39; H, 4.76. Found: C, 69.30; H, 4.87.
!
2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-
mannopyranosyl trichloroacetimidate (9). To a solution of 7 (5.88 g, 5.0 mmol) in
4:1 CH3CN H2O (450 mL) was added CAN (10.96 g, 20.0 mmol), and the mixture
was stirred at rt for 30 min, at the end of which time TLC (2:1 petroleum ether–
EtOAc) indicated that the reaction was complete. The mixture was extracted with

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
346
CHEN AND KONG
EtOAc, and washed with satd aq NaHCO3. The organic layer was concentrated under
reduced pressure, and purified by column chromatography (2:1 petroleum ether–
EtOAc) to afford 8 as a foamy solid (4.28 g, 80%). A mixture of 8 (4.28 g, 4.0 mmol),
trichloroacetonitrile (2.1 mL, 10 mmol), and anhyd potassium carbonate (4.28 g) in dry
dichloromethane (30 mL) was stirred overnight and then was filtered, and the filtrate
was concentrated in vacuo. The residue was purified by flash chromatography (2:1
petroleum ether–EtOAc) to give 9 as a foamy solid (4.37 g, 90%); [a]D ꢀ 48.1° (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.82 (s, 1 H, NH), 8.25–7.20 (m, 35 H, PhH),
6.55 (s, 1 H, H-1I), 6.14 (dd, 1 H, J3,4 = J4,5 =10.0 Hz, H-4II), 6.06 (dd, 1 H,
J
3,4 =J4,5 = 9.9 Hz, H-4I), 5.86 (dd, 1 H, H-2II), 5.70 (dd, 1 H, J2,3 = 2.7 Hz, J3,4 =10.0
Hz, H-3II), 5.37–5.36 (m, 2 H, H-1II, H-2I), 4.74–4.69 (m, 2 H), 4.57–4.45 (m, 4 H),
4.33 (dd, 1 H, J5,6 =2.6 Hz, J6,6 = 12.1 Hz, H-6).
Anal. Calcd for C63H50Cl3NO18: C, 62.25; H, 4.12. Found: C, 62.00; H, 4.14.
!
p-Methoxyphenyl 3-O-Allyl-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-
2,4,6-tri-O-benzoyl-a-D-mannopyranoside (10). 3-O-Allyl-2,4,6-tri-O-benzoyl-a-D-
mannopyranosyl trichloroacetimidate (5, 1.35 g, 2.0 mmol) and p-methoxyphenyl
2,4,6-tri-O-benzoyl-a-D-mannopyranoside (3, 1.20 g, 2.0 mmol) were dried together
under high vacuum for 2 h, then dissolved in anhyd CH2Cl2 (20 mL). TMSOTf (30 mL,
0.08 equiv) was added dropwise at ꢀ 25°C with N2 protection. The reaction mixture
was stirred for 3 h, during which time the temperature was gradually warmed to
ambient temperature. Then the mixture was neutralized with triethylamine, concen-
trated and purified by flash chromatography (2:1 petroleum ether–EtOAc) to afford 10
1
(1.89 g, 85%); [a]D ꢀ 9.0° (c 1.1, CHCl3); H NMR (400 MHz, CDCl3): d 8.21–7.26
(m, 30 H, PhH), 7.00 (d, 2 H, J=9.1 Hz, p-CH3O PhH), 6.75 (d, 2 H, J=9.1 Hz, p-
CH3O PhH), 5.98 (dd, 1 H, J3,4 = J4,5 =9.8 Hz, H-4II), 5.86 (dd, 1 H, J1,2 = 1.8 Hz,
J2,3 =3.4 Hz, H-2II), 5.74 (dd, 1 H, J3,4 = J4,5 =9.9 Hz, H-4I), 5.66 (d, 1 H, H-1II), 5.43
(m, 1 H, CH2 CHCH2 ), 5.31 (d, 1 H, J1,2 = 1.8 Hz, H-1I), 5.20 (dd, 1 H, H-2I),
4.87–4.74 (m, 2 H, CH2 CHCH2 ), 4.79 (dd, 1 H, H-3II), 4.60–4.56 (m, 2 H),
4.51–4.44 (m, 2 H), 4.35 (m, 1 H), 4.28(m, 1 H, H-6), 3.91–3.88 (dd, 1 H), 3.76–3.63
(m, 2 H, CH2 CHCH2 ), 3.75 (s, 3 H, CH3O).
Anal. Calcd for C64H56O18: C, 69.06; H, 5.04. Found: C, 69.24; H, 5.03.
!
p-Methoxyphenyl 2,4,6-Tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-
O-benzoyl-a-D-mannopyranoside (11). To a solution of 10 (2.22 g, 2.0 mmol) in
anhyd CH3OH (50 mL) was added PdCl2 (0.22 g), and the mixture was stirred at 40°C
for 3 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. The
residue was passed through a silica-gel column with 2:1 petroleum ether–EtOAc as the
1
eluent to give 11 as a syrup (1.82 g, 85%): [a]D +4.3° (c 1.0, CHCl3); H NMR (400
MHz, CDCl3): d 8.20–7.25 (m, 30 H, PhH), 7.01 (d, 2 H, J=9.1 Hz, p-CH3O PhH),
6.75 (d, 2 H, J =9.1 Hz, p-CH3O PhH), 5.99 (dd, 1 H, J3,4 =J4,5 = 9.8 Hz, H-4II), 5.84
(dd, 1 H, J1,2 =1.6 Hz, J2,3 =3.0 Hz, H-2II), 5.67 (d, 1 H, H-1II), 5.60 (dd, 1 H,
J
J
3,4 =J4,5 = 9.7 Hz, H-4I), 5.38 (s, 1 H, H-1I), 5.10 (br, 1 H, H-2I), 4.79 (dd, 1 H,
2,3 =3.3 Hz, J3,4 =9.7 Hz H-3II), 4.62–4.58 (m, 2 H), 4.48–4.34 (m, 4 H), 4.21 (dd, 1
H, J=3.0 Hz, J =9.8 Hz, H-3II), 3.74 (s, 3 H, CH3O).
Anal. Calcd for C61H52O18: C, 68.28; H, 4.85. Found: C, 68.55; H, 4.94.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
!
a-(1 3)-LINKED MANNOHEXAOSE AND MANNOOCTAOSE
347
!
3-O-Allyl-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-
a-D-mannopyranosyl trichloroacetimidate (13). To a solution of 10 (5.56 g, 5.0
mmol) in 4:1 CH3CN H2O (450 mL) was added CAN (10.96 g, 20.0 mmol), and the
mixture was stirred at rt for 30 min, at the end of which time TLC (2:1 petroleum
ether–EtOAc) indicated that the reaction was complete. The mixture was extracted
with EtOAc, and washed with satd aq NaHCO3. The organic layer was concentrated
under reduced pressure, and purified by column chromatography (2:1 petroleum ether–
EtOAc) to afford 12 as a foamy solid (4.02 g, 80%). A mixture of 12 (4.02 g, 4.0
mmol), trichloroacetonitrile (2.1 mL), and anhydrous potassium carbonate (4.02 g) in
dry dichloromethane (30 mL) was stirred overnight and then was filtered, and the
filtrate was concentrated in vacuo. The residue was purified by flash chromatography
(4:1 petroleum ether–EtOAc) to give 13 (4.14 g, 90%) as a syrup; [a]D ꢀ 25.5° (c 1.0,
CHCl3);1H NMR (400 MHz, CDCl3): d 8.85 (s, 1 H, NH), 8.23–7.26 (m, 30 H, PhH),
6.58 (d, 1 H, J1,2 =1.2 Hz, H-1I), 6.10 (dd, 1 H, J3,4 = J4,5 =9.7 Hz, H-4II), 5.87 (br, 1 H,
H-2II), 5.81 (dd, 1 H, J3,4 = J4,5 =9.8 Hz, H-4I), 5.43 (m, 1 H, CH2 CHCH2 ), 5.28 (s,
1 H, H-1II), 5.22 (br, 1 H, H-2I), 4.89–4.65 (m, 2 H, CH2 CHCH2 ), 4.77–4.65 (m,
2 H), 4.56–4.50 (m, 3 H), 4.36 (m, 1 H, H-5), 4.26 (dd, 1 H, J5,6 =2.9 Hz, J6,6 =12.3
Hz, H-6), 3.90 (dd, 1 H, J =3.0 Hz, J= 9.7 Hz), 3.80–3.63 (m, 2 H, CH2 CHCH2 ).
Anal. Calcd for C59H50Cl3NO17: C, 61.54; H, 4.35. Found: C, 61.80; H, 4.33.
Methyl 3-O-Allyl-2,4,6-tri-O-benzoyl-a-D-mannopyranoside (15). To a solu-
tion of methyl 3-O-allyl-a-D-mannopyranoside[9] 14 (11.7 g, 50 mmol) in pyridine (40
mL) was added benzoyl chloride (21 mL, 180 mmol). After stirring the mixture at rt
overnight, TLC (3:1 petroleum ether–EtOAc) indicated that the reaction was complete.
Methanol (15 mL) was added to the reaction mixture, and stirring was continued for 10
min. Water (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
1
15 (27.3 g, 100%) as a foamy solid; [a]D ꢀ 34.4° (c 1.0, CHCl3); H NMR (400 MHz,
CDCl3): d 8.10–7.37 (m, 15 H, PhH), 5.82 (dd, 1 H, J3,4 =J4,5 = 9.8 Hz, H-4), 5.70 (m,
1 H, CH2 CHCH2 ), 5.58 (dd, 1 H, J1,2 =1.7 Hz, J2,3 =3.3 Hz, H-2), 5.19–5.02 (m, 2
H, CH2 CHCH2 ), 4.92 (d, 1 H, H-1), 4.68 (dd, 1 H, J5,6 =2.6 Hz, J6,6’ =12.1 Hz,
H-6II), 4.25 (m, 1 H, H-5), 4.14 (dd, 1 H, J5,6’ =4.9 Hz, H-6’), 4.14–3.97 (m, 2 H,
CH2 CHCH2 ), 3.48 (s, 3 H, CH3O).
Anal. Calcd for C31H30O9: C, 68.13; H, 5.49. Found: C, 68.05; H, 5.51.
Methyl 2,4,6-Tri-O-benzoyl-a-D-mannopyranoside (16). To a solution of 15
(5.46 g, 10.0 mmol) in anhyd CH3OH (80 mL) was added PdCl2 (0.55 g), and the mixture
was stirred at 40°C for 2 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 The residue was passed through a silica-gel column with 3:1 petroleum
ether–EtOAc as the eluent to give 16 as a syrup (4.55 g, 90%); [a]D + 7.1° (c 1.0, CHCl3);
1H NMR (400 MHz, CDCl3): d 8.07–7.37 (m, 15 H, PhH), 5.71 (dd, 1 H, J3,4 = J4,5 =9.9
Hz, H-4), 5.42 (dd, 1 H, J1,2 =1.7 Hz, J2,3 =3.4 Hz, H-2), 4.95 (d, 1 H, H-1), 4.68
(dd, 1 H, J5,6 =2.5 Hz, J6,6’ =12.1 Hz, H-6), 4.47 (dd, 1 H, J5,6’ = 4.7 Hz, H-6’), 4.41
(dd, 1 H, H-3), 4.28 (m, 1 H, H-5), 3.48 (s, 3 H, CH3O), 3.47 (br, 1 H, OH).
Anal. Calcd for C28H26O9: C, 66.40; H, 5.14. Found: C, 66.55; H, 5.13.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
348
CHEN AND KONG
!
Methyl 3-O-Allyl-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-
benzoyl-a-D-mannopyranoside (17). The monosaccharide donor 5 (3.38 g, 5.0
mmol) and the monosaccharide acceptor 16 (2.53 g, 5.0 mmol) were dried together
under high vacuum for 2 h, then dissolved in anhyd CH2Cl2 (40 mL). TMSOTf (50 mL,
0.05 equiv) was added dropwise at ꢀ 25°C with N2 protection. The reaction mixture
was stirred for 3 h, during which time the temperature was gradually warmed to
ambient temperature. Then the mixture was neutralized with triethylamine, concen-
trated and purified by flash chromatography (3:1 petroleum ether–EtOAc) to afford 17
1
(4.34 g, 85%) as a syrup; [a]D ꢀ 32.9° (c 0.9, CHCl3); H NMR (400 MHz, CDCl3): d
8.11–7.25 (m, 30 H, PhH), 5.97 (dd, 1 H, J3,4 =J4,5 =10.0 Hz, H-4II), 5.72 (dd, 1 H,
J
3,4 =J4,5 = 9.9 Hz, H-4I), 5.67 (dd, 1 H, J1,2 = 1.7 Hz, J2,3 =3.1 Hz, H-2II), 5.41 (m, 1 H,
CH2 CH CH2 ), 5.21–5.18 (m, 2 H, H-1II, H-2I), 4.95 (d, 1 H, J1,2 =1.4 Hz, H-1I),
4.87–4.72 (m, 2 H, CH2 CH CH2 ), 4.70-4.66 (dd, 1 H, J=2.6 Hz, J =12.1 Hz),
4.61–4.57 (m, 2 H), 4.52–4.48 (dd, 1 H), 4.35–4.26 (m, 3 H), 3.89–3.86 (dd, 1 H),
3.76–3.59 (m, 2 H, CH2 CH CH2 ), 3.42 (s, 3 H, CH3O); 13C NMR (100 MHz,
CDCl3): d 166.26, 166.26, 165.78, 165.71, 165.22, 165.00 (6 PhCO), 133.85, 133.71,
133.64, 133.23, 133.14, 133.14, 132.92, 129.98, 129.89, 129.81, 129.66, 129.47,
129.02, 128.81, 128.65, 128.51, 128.41, 128.38, 128.34, 117.57 (CH2 CH CH2 ),
99.67, 98.69 (C-1), 75.47, 73.81, 71.69, 70.54, 69.86, 68.85, 68.85, 68.75, 67.86, 63.12,
62.99 (C-2, 3, 4, 5, 6, CH2 CH CH2 ), 55.52 (CH3O).
Anal. Calcd for C58H52O17: C, 68.24; H, 5.10. Found: C, 68.30; H, 5.07.
!
Methyl 2,4,6-Tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-
a-D-mannopyranoside (18). To a solution of 17 (4.34 g, 4.3 mmol) in anhyd CH3OH
(80 mL) was added PdCl2 (0.4 g), and the mixture was stirred at 40°C for 3 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. The residue was
purified on a silica-gel column with 2:1 petroleum ether–EtOAc as the eluent to give 18
1
as a syrup (3.75 g, 90%); [a]D ꢀ 27.4° (c 0.8, CHCl3); H NMR (400 MHz, CDCl3): d
8.18–7.28 (m, 30 H, PhH), 5.97 (dd, 1 H, J3,4 =J4,5 =10.0 Hz, H-4II), 5.65 (dd, 1 H,
J
J
1,2 =1.2 Hz, J2,3 =3.1 Hz, H-2II), 5.59 (dd, 1 H, J3,4 =J4,5 =9.7 Hz, H-4I), 5.27 (d, 1 H,
1,2 =1.2 Hz, H-1II), 5.07 (dd, 1 H, J1,2 =1.4 Hz, J2,3 =3.1 Hz, H-2I), 4.94 (d, 1 H, J1,2 =1.4
Hz, H-1I), 4.71–4.67 (dd, 1 H, J=2.5 Hz, J= 12.1 Hz), 4.61–4.57 (m, 2 H), 4.48–4.44
(dd, 1 H, J =4.5 Hz, J= 12.2 Hz), 4.40–4.34 (m, 2 H), 4.27–4.24 (m, 1 H), 4.19–4.16 (dd,
1 H, J=3.2 Hz, J=9.8 Hz), 3.42 (s, 3 H, CH3O), 2.40 (br, 1 H, OH); 13C NMR (100 MHz,
CDCl3): d 166.39, 166.14, 166.06, 165.73, 165.60, 165.07 (6 PhCO), 133.60, 133.41,
133.25, 132.98, 132.87, 129.91, 129.89, 129.83, 129.76, 129.69, 129.62, 129.27, 129.08,
128.97, 128.73, 128.46, 128.37, 128.32, 128.28 (6 Ph), 99.41, 98.52 (C-1), 75.79 (C-3),
72.33, 71.71, 69.78, 69.24, 68.72, 68.55, 68.40, 62.99, 62.75 (C-2,3,4,5,6), 55.39 (CH3O).
Anal. Calcd for C55H48O17: C, 67.35; H, 4.90, Found: C, 67.30; H, 4.98.
!
p-Methoxyphenyl 2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-
!
tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyrano-
!
syl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranoside (19). The disaccharide donor 9
(1.21 g, 1.0 mmol) and the disaccharide acceptor 11 (1.07 g, 1.0 mmol) were dried
together under high vacuum for 2 h, then dissolved in anhyd CH2Cl2 (30 mL).
TMSOTf (20 mL, 0.1 equiv) was added dropwise at ꢀ 25°C with N2 protection. The

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
!
a-(1 3)-LINKED MANNOHEXAOSE AND MANNOOCTAOSE
349
reaction mixture was stirred for 3 h, during which time the temperature was gradually
warmed to ambient temperature. Then the mixture was neutralized with triethylamine,
concentrated and purified by flash chromatography (2:1 petroleum ether–EtOAc) to
1
afford 19 (1.70 g, 80%) as a syrup; [a]D ꢀ 45.5° (c 1.1, CHCl3); H NMR (400 MHz,
CDCl3): d 8.23–7.26 (m, 65 H, PhH), 7.03 (d, 2 H, J=9.2 Hz, p-CH3O PhH), 6.78 (d,
2 H, J=9.2 Hz, p-CH3O PhH), 6.05 (dd, 1 H, J3,4 =J4,5 = 9.8 Hz, H-4IV), 5.97–5.90
(m, 4 H, H-4III, H-4II, H-4I, H-2IV), 5.70 (d, 1 H, J1,2 = 1.7 Hz, H-1IV), 5.57 (dd, 1 H,
J
2,3 = 3.1 Hz, J3,4 = 9.8 Hz, H-3IV), 5.44 (d, 1 H, J1,2 =1.4 Hz, H-1III), 5.34 (m, 1 H, H-
2III), 5.19 (m, 2 H, H-2II, H-2I), 4.97 (br, 1 H, H-1II), 4.93 (br, 1 H, H-1I), 4.82 (dd, 1
H, J2,3 = 3.3 Hz, J3,4 =9.7 Hz, H-3III), 4.64 (m, 1 H), 4.56 (m, 1 H), 4.51–4.49 (m, 2 H),
4.42–4.38 (m, 2 H), 4.33–4.29 (m, 2 H), 4.11–3.96 (m, 6 H), 3.76 (s, 3 H, CH3O); 13C
NMR (100MHz, CDCl3): d 166.18, 166.18, 165.94, 165.94, 165.82, 165.82, 165.53,
165.22, 165.17, 165.06, 165.06, 164.74, 164.65 (13 PhCO), 155.54, 149.68 (CH3O
C6H4
O
), 133.93, 133.68, 133.63, 133.59, 133.47, 133.40, 133.20, 133.13, 132.98,
132.92, 130.15, 130.08, 130.02, 129.97, 129.87, 129.84, 129.76, 129.67, 129.28,
129.06, 128.98, 128.93, 128.87, 128.63, 128.57, 128.46, 128.26, 128.18 (Ph), 118.03,
114.76 (CH3O C6H4
O
), 99.37, 99.31, 99.04, 96.59 (4 C-1), 76.92, 76.78, 76.53
(3 C-3), 71.63, 71.50, 71.50, 70.19, 69.93, 69.56, 69.50, 69.45, 69.26, 68.26, 67.43,
67.13, 66.16, 63.06, 62.56, 62.24, 62.24 (C-2, 3, 4, 5, 6), 55.67 (CH3O).
Anal. Calcd for C122H100O35: C, 68.93; H, 4.71, Found: C, 68.79; H, 4.73.
!
2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-
!
!
mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-
O-benzoyl-a-D-mannopyranose (20). To a solution of 19 (2.12 g, 1.0 mmol) in 4:1
CH3CN H2O (100 mL) was added CAN (2.19 g, 4.0 mmol), and the mixture was
stirred at rt for 1 h, at the end of which time TLC (1.5:1 petroleum ether–EtOAc)
indicated that the reaction was complete. The mixture was extracted with EtOAc, and
washed with satd aq NaHCO3. The organic layer was concentrated under reduced
pressure, and purified by column chromatography (1.5:1 petroleum ether–EtOAc) to
1
afford 20 as a syrup (1.51 g, 75%); [a]D ꢀ 51.7° (c 1.0, CHCl3); H NMR (400 MHz,
CDCl3): d 8.21–7.16 (m, 65 H, PhH), 6.65 (br, 1 H, OH), 6.03 (dd, 1 H, J3,4 = J4,5
=
10.0 Hz, H-4IV), 5.89 (m, 3 H, H-4III, H-4II, H-4I), 5.71 (br, 1 H, H-2IV), 5.52 (dd,1 H,
J
2,3 = 3.1 Hz, H-3IV), 5.48 (s, 1 H, H-1IV), 5.30 (s, 1 H, H-1III), 5.28 (m, 1 H, H-2III),
5.15 (m, 2 H, H-2II, H-2I), 4.92 (s, 1 H, H-1II), 4.87 (s, 1 H, H-1I), 4.74–4.67 (m, 2
H), 4.55–4.53 (m, 2 H), 4.41–4.32 (m, 3 H), 4.27–4.24 (m, 2 H), 4.06–3.91 (m, 6 H).
Anal. Calcd for C115H94O34: C, 68.38; H, 4.66, Found: C, 68.45; H, 4.64.
!
2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-
!
!
mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-
O-benzoyl-a-D-mannopyranosyl trichloroacetimidate (21). A mixture of 20 (1.51 g,
0.75 mmol), trichloroacetonitrile (0.42 mL), and anhyd potassium carbonate (1.51 g) in
dry dichloromethane (20 mL) was stirred overnight and then filtered, and the filtrate
was concentrated in vacuo. The residue was purified by flash chromatography (1.5:1
petroleum ether–EtOAc) to give 21 (1.30 g, 80%) as a syrup; [a]D ꢀ 3.9° (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.80 (br, 1 H, NH), 8.20–7.17 (m, 65 H,
PhH), 6.55 (s, 1 H, H-1I), 6.11 (dd, 1 H, J3,4 = J4,5 =10.0 Hz, H-4IV), 5.98–5.85 (m, 4
H, H-4III, H-4II, H-4I, H-2IV), 5.53 (dd, 1 H, J2,3 = 3.1 Hz, J3,4 =10.0 Hz, H-3IV), 5.35

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
350
CHEN AND KONG
(d, 1 H, J1,2 = 1.7 Hz, H-1IV), 5.31 (m, 1 H, H-2III), 5.15 (m, 2 H, H-2II, H-2I), 4.96 (d,
1 H, J1,2 = 1.4 Hz, H-1III), 4.88 (d, 1 H, H-1II), 4.71–4.63 (m, 2 H), 4.52–4.45 (m, 3
H), 4.37–4.33 (m, 2 H), 4.28–4.25 (m, 2 H), 4.06–3.91 (m, 6 H).
Anal. Calcd for C117H94Cl3NO34: C, 64.92; H, 4.35, Found: C, 64.63; H, 4.37.
!
Methyl 3-O-Allyl-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-
!
benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-
!
(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranoside (22). The disaccharide donor 13
(1.15 g, 1.0 mmol) and the disaccharide acceptor 18 (0.98 g, 1.0 mmol) were dried
together under high vacuum for 2 h, then dissolved in anhyd CH2Cl2 (40 mL).
TMSOTf (20 mL, 0.1 equiv) was added dropwise at ꢀ 25°C with N2 protection. The
reaction mixture was stirred for 3 h, during which time the temperature was gradually
warmed to ambient temperature. Then the mixture was neutralized with triethylamine,
concentrated and purified by flash chromatography (2:1 petroleum ether–EtOAc) to
1
afford 22 as a foamy solid (1.57 g, 80%); [a]D ꢀ 42.4° (c 1.0, CHCl3); H NMR (400
MHz, CDCl3): d 8.19–7.17 (m, 60 H, PhH), 5.98 (dd, 1 H, J3,4 =J4,5 = 10.0 Hz, H-4IV),
5.89 (dd, 1 H, J3,4 = J4,5 =10.0 Hz, H-4III), 5.82 (dd, 1 H, J3,4 = J4,5 =10.0 Hz, H-4II),
5.68 (m, 1 H, H-2IV), 5.64 (dd, 1 H, J3,4 =J4,5 =9.9 Hz, H-4I), 5.36 (m, 1 H, CH2
CH CH2 ), 5.29–5.27 (m, 2 H, H-2III, H-1IV), 5.13 (m, 1 H, H-2II), 5.02 (m, 1 H, H-
2I), 4.96 (d, 1 H, J1,2 =1.5 Hz, H-1III), 4.92 (d, 1 H, J1,2 = 1.6 Hz, H-1II), 4.80–4.66 (m,
3 H, CH2 CH CH2 , H-1I), 4.69 (m, 1 H), 4.61–4.55 (m, 2 H), 4.49–4.45 (dd, 1
H), 4.39–4.27 (m, 4 H), 4.21 (dd, 1 H), 3.99–3.94 (m, 4 H), 3.88 (m, 1 H, H-5), 3.79–
3.72 (m, 2 H), 3.67–3.47 (m, 2 H, CH2 CH CH2 ), 3.44 (s, 3 H, CH3O); 13C
NMR (100 MHz, CDCl3): d 166.27, 166.15, 165.93, 165.93, 165.85, 165.70, 165.56,
165.29, 165.08, 164.95, 164.90, 164.82 (12 PhCO), 133.87, 133.75, 133.57, 133.44,
133.17, 133.12, 133.01, 132.94, 132.90, 132.80, 130.00, 129.82, 129.78, 128.95,
128.79, 128.52, 128.48, 128.41, 128.25 (Ph), 117.29 (CH2 CH CH2 ), 99.33,
99.19, 99.00, 98.66 (4 C-1), 76.82, 76.44, 76.10, 73.95, 71.61, 71.33, 71.33, 70.36,
69.78, 69.32, 69.32, 68.76, 68.76, 68.47, 67.49, 67.49, 67.48, 63.05, 62.61, 62.47, 62.45
(C-2,3,4,5,6, CH2 CH CH2 ), 55.55 (CH3O).
Anal. Calcd for C112H96O33: C, 68.29; H, 4.88, Found: C, 68.42; H, 4.96.
!
Methyl 2,4,6-Tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-
!
!
a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-
tri-O-benzoyl-a-D-mannopyranoside (23). To a solution of 22 (1.57 g, 0.8 mmol) in
anhyd CH3OH (50 mL) was added PdCl2 (0.16 g), and the mixture was stirred for 4 h at
40°C, at the end of which time TLC (1.5:1 petroleum ether–EtOAc) indicated that the
reaction was complete. The mixture was filtered, and the filtrate was concentrated. The
residue was purified on a silica-gel column with 1.5:1 petroleum ether–EtOAc as the
1
eluent to give 23 as a syrup (1.23 g, 80%); [a]D ꢀ 32.1° (c 1.0, CHCl3); H NMR (400
MHz, CDCl3): d 8.08–7.17 (m, 60 H, PhH), 5.97 (dd, 1 H, J3,4 =J4,5 =9.9 Hz, H-4IV),
5.87 (dd, 1 H, J3,4 = J4,5 =9.9 Hz, H-4III), 5.81 (dd, 1 H, J3,4 = J4,5 =9.8 Hz, H-4II), 5.66
(m, 1 H, J1,2 = 1.7 Hz, J2,3 =3.3 Hz, H-2IV), 5.47 (dd, 1 H, J3,4 =J4,5 =9.9 Hz, H-4I), 5.28
(d, 1 H, H-1IV), 5.25 (dd, 1 H, H-2III), 5.11 (dd, 1 H, H-2II), 4.94 (d, 1 H, J1,2 =1.4 Hz,
H-1III), 4.89–4.88 (m, 2 H, H-1II, H-2I), 4.84 (d, 1 H, H-1I), 4.68 (dd, 1 H, J5,6 =2.4 Hz,
J
6,6’ =12.1 Hz, H-6IV), 4.57 (dd, 1 H, H-3IV), 4.52 (dd, 1 H, J5,6 = 2.3 Hz, J6,6’ = 12.2 Hz,

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
!
a-(1 3)-LINKED MANNOHEXAOSE AND MANNOOCTAOSE
351
H-6III),4.46 (dd, 1 H, J5,6’ = 4.6 Hz, J6,6’ =12.1 Hz, H-6’IV), 4.36–4.20 (m, 5 H), 4.05–
3.88 (m, 7 H), 3.43 (s, 3 H, CH3O); 13C NMR (100 MHz, CDCl3): d 166.35, 166.27,
166.15, 165.92, 165.85, 165.78, 165.72, 165.48, 165.27, 165.11, 165.08, 164.96 (12
PhCO), 133.74, 133.60, 133.54, 133.39, 133.30, 133.11, 132.94, 132.87, 130.14, 130.07,
129.99, 129.89, 129.85, 129.76, 129.32, 128.94, 128.84, 128.78, 128.55, 128.52, 128.40
(Ph), 99.16, 99.16, 98.95, 98.64 (4 C-1), 76.56, 76.11, 76.01, 72.32, 71.61, 71.47, 71.38,
69.76, 69.57, 69.34, 68.77, 68.76, 68.41, 68.40, 67.46, 67.43, 63.05, 62.28, 62.58,
62.28, 62.28 (C-2,3,4,5,6), 55.55 (CH3O).
Anal. Calcd for C109H92O33: C, 67.84; H, 4.77, Found: C, 67.61; H, 4.79.
!
Methyl 2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-ben-
!
!
zoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-
!
2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopy-
ranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranoside (24). The disaccharide
!
donor 9 (0.30 g, 0.25 mmol) and the tetrasaccharide acceptor 23 (0.48 g, 0.25 mmol)
were dried together under high vacuum for 2 h, then dissolved in anhyd CH2Cl2 (10
mL). TMSOTf (10 mL, 0.2 equiv) was added dropwise at ꢀ 25°C with N2 protection.
The reaction mixture was stirred for 3 h, during which time the temperature was
gradually warmed to ambient temperature. Then the mixture was neutralized with
triethylamine, concentrated and purified by flash chromatography (1.5:1 petroleum
1
ether–EtOAc) to afford 24 (0.56 g, 75%) as a syrup; [a]D ꢀ 86.3° (c 1.1, CHCl3); H
NMR (400 MHz, CDCl3): d 8.17–7.08 (m, 95 H, PhH), 5.96 (dd, 1 H, J3,4 = J4,5 =10.0
Hz, H-4VI), 5.89–5.75 (m, 5 H, H-4V, IV, III, II, I), 5.65 (dd, 1 H, J1,2 =1.8 Hz, J2,3 =3.2
Hz, H-2VI), 5.50 (dd, 1 H, H-3VI), 5.27 (d, 1 H, H-1VI), 5.25 (m, 1 H, H-2V), 5.12 (m, 2
H, H-2IV, III), 5.07 (m, 2 H, H-2II, H-2I), 4.94 (d, 1 H, J1,2 = 1.5 Hz, H-1V), 4.88 (d, 1 H,
J
1,2 = 1.7 Hz, H-1IV), 4.82 (m, 3 H, H-1III, II, I), 4.69 (dd, 1 H, J5,6 = 2.5 Hz, J6,6 =12.1
Hz, H-6VI), 4.59–4.53 (m, 2 H), 4.47–4.43 (dd, 1 H, J5,6’ =4.6 Hz, J6,6’ = 12.1 Hz,
H-6’VI), 4.36–4.17 (m, 8 H), 4.02–3.81 (m, 11 H), 3.43 (s, 3 H, CH3O); 13C NMR
(100 MHz, CDCl3): d 166.28, 166.17, 165.93, 165.87, 165.84, 165.81, 165.74,
165.68, 165.53, 165.34, 165.31, 165.06, 165.06, 164.99, 164.99, 164.94, 164.94,
164.70, 164.59 (19 PhCO), 133.73, 133.56, 133.41, 133.31, 133.25, 133.20, 133.15,
133.10, 133.05, 132.94, 132.84, 130.07, 129.98, 129.89, 129.80, 128.75, 129.72,
129.64, 129.25, 129.21, 129.16, 128.93, 128.80, 128.51, 128.42, 128.39, 128.32,
128.20, 128.12 (Ph), 99.22, 99.22, 98.96, 98.88, 98.85, 98.65 (6 C-1), 76.90, 76.83,
76.66, 76.46, 70.11, 69.76, 69.51, 69.36, 69.29, 69.22, 69.16, 68.75, 68.44, 67.48,
67.07, 66.09, 63.04, 62.60, 62.19 (C-2,3,4,5,6), 55.53 (CH3O).
Anal. Calcd for C170H140O50: C, 68.46; H, 4.70, Found: C, 68.22; H, 4.72.
!
!
Methyl a-D-Mannopyranosyl-(1 3)-a-D-mannopyranosyl-(1 3)-a-D-manno-
!
!
!
pyranosyl-(1 3)-a-D-mannopyranosyl-(1 3)-a-D-mannopyranosyl-(1 3)-a-D-
mannopyranoside (25). Compound 24 (0.45 g, 0.15 mmol) was dissolved in a satd
solution of NH3 in anhyd CH3OH (20 mL). After one week at rt, the reaction mixture
was concentrated, and the residue was purified by chromatography on Sephadex LH-20
1
(MeOH) to afford 25 as a syrup (0.14 g, 90%); [a]D +84.9° (c 1.0, CH3OH); H NMR
(400 MHz, D2O): d 5.14–5.10 (m, 5 H, H-1VI, V, VI, III, II), 4.75 (s, 1 H, H-1I), 4.24 (m,
4 H), 4.08–3.65 (m, 32 H), 3.42 (s, 3 H, CH3O); 13C NMR (100 MHz, D2O): d 104.72,

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
352
CHEN AND KONG
104.62, 104.62, 104.62, 104.62, 103.13 (C-1), 80.68, 80.58, 80.48, 80.30, 80.21, 75.95,
75.86, 75.80, 75.09, 72.75, 72.42, 72.06, 71.97, 69.27, 68.53, 68.46, 68.38, 63.43, 63.22
(C-2,3,4,5,6), 57.15 (CH3O); JC1–H1 =170.0–171.9 Hz; MALDI-TOF MS Calcd for
C37H64O31: [M] 1004.3, Found: [M +Na] 1027.8.
!
Methyl 2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-ben-
!
!
zoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-
!
2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopy-
ranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-
a-D-mannopyranosyl-(1 3)-2,4,6-tri-O-benzoyl-a-D-mannopyranoside (26). The
!
!
!
tetrasaccharide donor 21 (0.54 g, 0.25 mmol) and the tetrasaccharide acceptor 23
(0.48 g, 0.25 mmol) were dried together under high vacuum for 2 h, then dissolved in
anhyd CH2Cl2 (10 mL). TMSOTf (10 mL, 0.2 equiv) was added dropwise at ꢀ 25°C
with N2 protection. The reaction mixture was stirred for 3 h, during which time the
temperature was gradually warmed to ambient temperature. Then the mixture was
neutralized with triethylamine, concentrated and purified by flash chromatography
(1.2:1 petroleum ether–EtOAc) to afford 26 (0.74 g, 75%); [a]D ꢀ 49.4° (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.16–7.05 (m, 125 H, PhH), 5.96–5.74 (m, 8
H, H-4VIII, VII, VI, V, IV, III, II, I), 5.65 (m, 1 H, H-2VIII), 5.49 (dd, 1 H, H-3VIII), 5.26 (d,
1 H, J1,2 = 1.4 Hz, H-1VIII), 5.24 (m, 1 H, H-2VII), 5.11–5.04 (m, 5 H, H-2VI, V, IV, III, II),
4.94 (d, 1 H, J1,2 =1.4 Hz, H-1VII), 4.87 (d, 1 H, J1,2 =1.6 Hz, H-1VI), 4.81–4.78 (m, 4
H, H-1V, IV, III, II), 4.68 (dd, 1 H), 4.59–4.51 (m, 2 H), 4.45 (dd, 1 H), 4.36–4.16 (m,
11 H), 4.01–3.82 (m, 18 H), 3.43 (s, 3 H, CH3O); 13C NMR (100 MHz, CDCl3): d
166.28, 166.16, 165.93, 165.87, 165.83, 165.83, 165.79, 165.77, 165.73, 165.68,
165.52, 165.31, 165.31, 165.31, 165.31, 165.05, 165.05, 164.99, 164.97, 164.94,
164.94, 164.91, 164.91, 164.70, 164.57 (25 PhCO), 133.74, 133.58, 133.57, 133.53,
133.47, 133.42, 133.34, 133.30, 133.26, 133.23, 133.16, 133.13, 133.09, 133.03,
132.93, 132.86, 130.14, 130.11, 130.09, 129.98, 129.90, 129.89, 129.80, 129.76,
129.74, 129.25, 129.21, 129.15, 129.03, 128.92, 128.88, 128.79, 128.55, 128.51,
128.41, 128.39, 128.29, 128.20, 128.12 (Ph), 99.21, 99.21, 98.97, 98.89, 99.87, 99.87,
98.81, 98.65 (8 C-1), 76.46, 71.60, 71.44, 71.26, 70.11, 69.76, 69.51, 69.30, 69.22,
68.75, 68.44, 67.48, 67.11, 66.10, 63.02, 62.55, 62.18 (C-2,3,4,5,6), 55.55 (CH3O).
Anal. Calcd for C224H184O66: C, 68.43; H, 4.68, Found: C, 68.64; H, 4.76.
!
!
Methyl a-D-Mannopyranosyl-(1 3)-a-D-mannopyranosyl-(1 3)-a-D-manno-
!
!
!
pyranosyl-(1 3)-a-D-mannopyranosyl-(1 3)-a-D-mannopyranosyl-(1 3)-a-D-
!
!
mannopyranosyl-(1 3)-a-D-mannopyranosyl-(1 3)-a-D-mannopyranoside (27).
Compound 26 (0.59 g, 0.15 mmol) was dissolved in a satd solution of NH3 in anhyd
CH3OH (30 mL). After a week at rt, the reaction mixture was concentrated, and the
residue was purified by chromatography on Sephadex LH-20 (MeOH) to afford 27 as a
1
syrup (0.18 g, 90%); [a]D +87.7° (c 1.0, CH3OH); H NMR (400 MHz, D2O): d 5.16–
5.14 (m, 8 H, H-1VIII, VII, VI, V, VI, III, II, I), 4.26 (s, 7 H), 4.10–3.69 (m, 41 H), 3.44 (s, 3
H, CH3O); 13C NMR (100 MHz, D2O): d 104.75, 104.75, 104.63, 104.63, 104.63,
104.63, 104.63, 103.19 (8 C-1), 80.72, 80.61, 80.50, 75.97, 75.89, 75.82, 75.12, 72.78,
72.46, 72.09, 71.98, 69.30, 68.62, 68.56, 68.49, 68.41, 63.57, 63.45, 63.25 (C-2,3,4,5,6),
57.18 (CH3O); MALDI-TOF MS Calcd for C49H84O41: [M] 1328.4, Found: [M+ Na]
1352.0.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
!
a-(1 3)-LINKED MANNOHEXAOSE AND MANNOOCTAOSE
353
ACKNOWLEDGMENTS
This work was supported by The Chinese Academy of Sciences (RCEES9904),
The National Natural Science Foundation of China (Projects 30070185 and 39970864),
and The Ministry of Science and Technology.
REFERENCES
1. Ogawa, T.; Yamamoto, H. Synthetic studies on cell surface glycans. Part XXXIII.
Synthesis of a model linear mannohexaose for the backbone structure of fruit body
polysaccharide of Tremella fuciformis and Dictyophora indusiata Fisch. Agric.
Biol. Chem. 1985, 49, 475–482.
2. Cherniak, R.; Reiss, E.; Slodki, M.E.; Plattner, R.D.; Blumer, R.D. Structure and
antigenic activity of the capsular polysaccharide from Cryptococcus neoformans
serotype A. Mol. Immunol. 1980, 17, 1025–1031.
3. Saito, K.; Komae, A.; Kakuta, M.; Van Damme, E.J.M.; Peumans, W.J.; Goldstein,
I.J.; Misaki, A. The a-mannose-binding lectin from leaves of the orchid twayblade
(Listera ovata). Application to separation of a-D-mannans from a-D-glucans. Eur. J.
Biochem. 1994, 223, 1064–1072.
4. Xiong, S.; Kong, F.; Yang, C. Improved synthesis of 1,3-anhydro-2,4-di-O-benzyl-
b-L-rhamnopyranose and 1,3-anhydro-2,4,6-tri-O-benzyl-b-D-mannopyranose.
Youji Huaxue 1994, 14, 280–285.
5. Ogawa, T.; Yamamoto, Y. Synthesis of a model, linear D-mannopentaose for the
nonreducing-end sequence of the cell-surface D-mannan of Escherichia coli, Can-
dida albicans, and Saccharomyces cerevisiae. Carbohydr. Res. 1985, 137, 79–87.
6. Schmidt, R.R. Anomeric-oxygen activation for glycoside synthesis: The trichloro-
acetimidate method. Adv. Carbohydr. Chem. Biochem. 1994, 50, 21–125.
7. Podlasek, C.A.; Wu, J.; Stripe, W.A.; Bondo, P.B.; Serianni, A.S. [13C]-Enriched
methyl aldopyranosides: Structural interpretations of 13C–1H spin coupling
1
constants and H chemical shifts. J. Am. Chem. Soc. 1995, 117, 8635–8644.
8. Mori, M.; Ito, Y.; Ogawa, T. A highly stereoselective and practical synthesis of
cyclomannohexaose, cyclo{ ! 4)-[a-D-Manp-(1 !4)-]5a-D-Manp-(1!}, a manno
isomer of cyclomaltohexaose. Carbohydr. Res. 1989, 192, 131–146.
9. Yang, G.; Kong, F.; Zhou, S. Selective 3-O-allylation and benzylation of methyl
D-manno-, L-rhamno-, and L-fucopyranoside. Carbohydr. Res. 1991, 211, 179–181.
Received January 21, 2002
Accepted May 21, 2002