An efficient and stereoselective synthesis of β-D-Arap-(1 → 2)-β-D-Galp-(1 → 3)-β-D-Galp-(1 → 4)-α-D-Manp, a tetrasaccharide fragment of Leishmania major lipophosphoglycan

Article abstract of DOI:10.1016/S0008-6215(01)00274-9

A tetrasaccharide fragment of Leishmania major lipophosphoglycan (which seems to be involved in a biological mechanism for the parasite transmission) has been synthesised using the thioglycoside, trichloroacetimidate and halide-exchange glycosylation procedures and step-wise chain elongation strategy.

Full text of DOI:10.1016/S0008-6215(01)00274-9

Carbohydrate Research 336 (2001) 243–248
www.elsevier.com/locate/carres
Rapid Communication
An efficient and stereoselective synthesis of
-Galp-(1“4)-
-Manp, a tetrasaccharide fragment of Leishmania
b-
D
-Arap-(1“2)-b-
D
-Galp-(1“3)-b-
D
a-
D
major lipophosphoglycan
Dmitry V. Yashunsky, Adrian P. Higson, Andrew J. Ross, Andrei V. Nikolaev*
School of Life Sciences, Di6ision of Biological Chemistry and Molecular Microbiology, Carnelley Building,
Uni6ersity of Dundee, Dundee DD1 4HN, UK
Received 29 August 2001; received in revised form 15 October 2001; accepted 17 October 2001
Abstract
A tetrasaccharide fragment of Leishmania major lipophosphoglycan (which seems to be involved in a biological
mechanism for the parasite transmission) has been synthesised using the thioglycoside, trichloroacetimidate and
halide-exchange glycosylation procedures and step-wise chain elongation strategy. © 2001 Elsevier Science Ltd. All
rights reserved.
Keywords: Carbohydrates; Oligomers; Glycosylation; Parasites
The surface lipophosphoglycan (LPG) pro-
duced by the insect dwelling infectious pro-
mastigote stage of all species of the
Leishmania parasite contains a polymeric sec-
chains (from 9 to 45%) seems to be a biologi-
cal mechanism for the detachment of the
infectious metacyclic promastigotes from the
mid-gut epithelial cells of the sand-fly vector3
prior to their transmission to a mammalian
host.
Recent reports from this laboratory dis-
closed the synthesis and biological evaluation
of phosphosaccharide fragments of the LPG
of L. dono6ani,4 L. mexicana5 and L. major6
tion consisting of b-
phosphate repeat units. In LPG of Leishmania
major,1 the
-galactose units are, in the main,
randomly substituted at O-3 with b- -Galp,
b- -Galp-(1“3)-b- -Galp and b- -Arap-
(1“2)-b- -Galp. The composition of the side-
D
-Galp-(1“4)-a-
D
-Manp
D
D
D
D
D
D
chains changes during the differentiation of
the parasite, presenting various biological
properties on the LPG.2 The increase of the
(the latter contained b-
only). Here we report the synthesis of a tetra-
saccharide b- -Arap-(1“2)-b- -Galp-(1“3)-
b- -Galp-(1“4)-a- -Manp (1), which is due
D
-Galp side-chains
D
D
proportion of b- -Arap-terminating side-
D
D
D
to be incorporated further in the preparation
of the phosphosaccharides 2 and 3 (Scheme 1)
using the tetrasaccharide H-phosphonate
derivative 4 and H-phosphonate methodol-
* Corresponding author. Tel.: +44-1382-344325; fax:
+44-1382-345517.
E-mail address: avnikolaev@bad.dundee.ac.uk (A.V. Niko-
laev).
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00274-9

244
D.V. Yashunsky et al. / Carbohydrate Research 336 (2001) 243–248
porary protections at O-3 and -6; Scheme 2)
was prepared starting from the diol 6.8 The
key step of the transformation was reductive
benzylidene ring cleavage in the diacetate
derivative 79 with NaBH3CN–MeSO3H sys-
tem (it was the only one from a big variety of
synthetic procedures of this kind,10 which did
work efficiently to produce compound 89).
Successive deacetylation (“9;9 77% from 6)
and 2,4-protection via 3,4-O-orthobenzoate
formation, 2-O-benzoylation and regioselec-
tive acidic cleavage of the orthobenzoate11
gave the 3-OH derivative 109 (77%). Standard
chloroacetylation resulted in selectively pro-
Scheme 1.
ogy.4–6 The phosphosaccharides 2 and 3 will
be used for the preparation of artificial
antigens.
tected compound 11. Glycosylation of the
D
-
mannose derivative 194a (unit A) with the
thioglycoside 11 in the presence of MeOTf
The synthetic plan leading to compound 5
(a direct precursor of the H-phosphonate 4)
was designed regarding that (1) the b-gly-
coside linkage between units C and B could be
prepared with participating group at C-2 in
the unit C and (2) the preparation of the A–B
block should precede the rest of the synthe-
sis.7a Thus, linear step-wise sequence A+B“
A–B+C“A–B–C+D was chosen to ensure
selective and efficient synthesis of the target
tetrasaccharide molecule.7b
,
and MS 4A provided stereoselectively the b-
linked disaccharide 129 (J1%,2% 7.8 Hz) in 80%
yield. It was further dechloroacetylated5 with
thiourea (“13,9 95%; the A–B block) fol-
lowed by the reaction with the
D
-galactosyl
trichloroacetimidate 20 (unit C) in the pres-
ence of TMSOTf12 to produce the b,b-linked
trisaccharide 149 (69%; J1%%,2%% 7.8 Hz). A rou-
tine sequence of protecting group manipula-
tion including deacetylation13 (“15) with HCl
in MeOH, acetalisation14 (“16) with 2,2-
The required unit B (in a form of the
ethylthio b- -galactoside 11 containing tem-
D
Scheme 2. Reagents and conditions: (a) Ac2O, pyridine; (b) NaBH3CN, MeSO3H, THF; (c) MeOH, MeONa ca.; (d) (1)
PhC(OEt)3, TsOH·H2O, DCM; (2) BzCl, pyridine; (3) 1:0.1:1000 TFA–H2O–DCM; (e) ClCH2COCl, pyridine, DCM; (f) 19,
,
MeOTf, MS 4A, DCM; (g) (NH2)2CS, 2,4,6-collidine, MeOH, DCM, D; (h) 20, TMSOTf ca., DCM; (i) HCl, MeOH, DCM; (j)
Me2C(OMe)2, TsOH·H2O; (k) 3:3:1000 TFA–H2O–DCM; (l) BzCN, Et3N, MeCN.

D.V. Yashunsky et al. / Carbohydrate Research 336 (2001) 243–248
245
,
Scheme 3. Reagents and conditions: (a) n-Bu4NBr, MS 4A, DCE, D; (b) (1) 100:1:1000 TFA–H2O–DCM; (2) H2, Pd(OH)2–C,
MeOH; (c) TBSCl, DMAP, DCE; (d) (1) BzCl, pyridine; (2) HBF4, MeCN; (e) DMTCl, DMAP, pyridine; (f) MeOH, MeONa
ca.
dimethoxypropane–TsOH, mild-acid pro-
moted cleavage of the mixed acetal (“17) and
selective 6-O-benzoylation15 with benzoyl cya-
nide afforded the monohydroxyl trisaccharide
derivative 189 (79% from 14) ready to be used
as the A–B–C glycosyl acceptor block.
Acknowledgements
The Wellcome Trust Project Grant sup-
ported this work and A.P.H. The research of
A.V.N. was supported by an International
Research Scholar’s award from the Howard
Hughes Medical Institute.
Glycosylation of the trisaccharide 18 with
the
D
-arabinopyranosyl chloride 2116 (unit D)
,
in the presence of n-Bu4NBr and MS 4A (the
halide-exchange procedure17) provided the
b,b,b-linked tetrasaccharide 229 (Scheme 3;
76%; J1%%%,2%%% 3.4 Hz) as a single product of the
reaction. Successive removal of isopropylidene
and benzyl groups produced the hexaol 23 in
97% yield. Unexpectedly, direct 6%-O-trityla-
tion of this polyol with DMTCl–DMAP–pyr-
idine system failed due to, probably, partial
migration of the 6%%-O-benzoyl group to the
4%%-O-position followed by bis-tritylation. Al-
ternatively, selective silylation of the hexaol 23
with TBSCl–DMAP in 1,2-dichloroethane led
smoothly to the 6%-O-TBS derivative 24, which
was then perbenzoylated followed by desilyla-
tion with HBF4 (“25) and tritylation with
DMTCl–DMAP to give the desired tetra-
saccharide derivative 59 in 70% overall yield.
Debenzoylation of compound 25 with cata-
lytic MeONa in MeOH produced the unpro-
tected tetrasaccharide 19 in 92% yield.
Appendix A. Analytical and spectroscopic
data
Ethyl 2,3-di-O-acetyl-4,6-O-benzylidene-1-
thio-i- -galactopyranoside (7).—Solid; mp
D
112–113 °C (EtOH); [h]2D0 +35° (c 1, CHCl3);
Rf 0.88 (solvent A, 1:9 MeOH–CH2Cl2);
(Anal. Found: C, 57.76; H, 6.12. C19H24O7S
requires C, 57.56; H, 6.10); lH (300 MHz; the
1
same for the all H NMR data) 1.32 (3 H, t, J
7.4, SCH2CH3), 2.09 and 2.10 (2×3 H, 2×s,
Ac), 2.70–3.00 (2 H, m, SCH2CH3), 3.59 (1 H,
br s, 5-H), 4.04 (1 H, dd, J5,6a 1.6, J6a,6b 12.5,
6-Ha), 4.37 (1 H, dd, J5,6b 1.4, 6-Hb), 4.44 (1
H, d, J3,4 3.5, 4-H), 4.48 (1 H, d, J1,2 10.0,
1-H), 5.01 (1 H, dd, J2,3 10.0, 3-H), 5.50 (1 H,
t, 2-H), 5.52 (1 H, s, PhCH) and 7.40–7.60 (5
H, m, Ph).
Ethyl 2,3-di-O-acetyl-6-O-benzyl-1-thio-i-
To summarise, we have successfully pre-
pared a unique tetrasaccharide related to b-
D
-galactopyranoside (8).—Amorphous solid;
D
-
[h]2D0 0° (c 1, CHCl3); Rf 0.28 (solvent B, 3:7
EtOAc–PhCH3); (Anal. Found: C, 57.64; H,
Arap enriched LPGs from L. major.

246
D.V. Yashunsky et al. / Carbohydrate Research 336 (2001) 243–248
ClCH2), 3.91 and 4.08 (AB-system, Jgem 12.1,
PhCH2), 4.14 (1 H, br d, J4,5 9.8, 5-H), 4.39 (1
H, dd, J5,6a 2.4, J6a,6b 12.4, 6-Ha), 4.54 (1 H, br
d, 6-Hb), 4.57 (1 H, t, J3,4 9.8, 4-H), 4.83 (1 H,
d, J1%,2% 7.8, 1%-H), 5.18 (1 H, dd, J3%,4% 3.3, J2%,3%
10.4, 3%-H), 5.45 (1 H, dd, 2%-H), 5.54 (1 H, d,
4%-H), 5.76 (1 H, dd, J1,2 1.9, J2,3 3.3, 2-H),
5.87 (1 H, dd, 3-H), 6.39 (1 H, d, 1-H) and
6.90–8.20 (35 H, 7×Ph).
6.79. C19H26O7S requires C, 57.27; H, 6.58);
lH 1.19 (3 H, t, J 7.5, SCH2CH3), 1.98 and
2.62 (2×3 H, 2×s, Ac), 2.58–2.77 (2 H, m,
SCH2CH3), 2.87 (1 H, br s, OH), 3.60–3.75 (3
H, m, 5-H, 6-Ha and 6-Hb), 4.13 (1 H, br d,
J3,4 3.0, 4-H), 4.37 (1 H, d, J1,2 9.9, 1-H), 4.46
and 4.51 (AB-system, Jgem 11.9, PhCH2), 4.89
(1 H, dd, J2,3 9.8, 3-H), 5.28 (1 H, t, 2-H) and
7.23 (5 H, m, Ph).
Ethyl 6-O-benzyl-1-thio-i-
D
-galactopyran-
2,4-Di-O-benzoyl-6-O-benzyl-i-
pyranosyl-(1“4)-1,2,3,6-tetra-O-benzoyl-h-
-mannopyranose (13).—Amorphous solid;
D
-galacto-
oside (9).—Amorphous solid; [h]2D0 +21° (c 1,
CHCl3); Rf 0.44 (solvent A); (Anal. Found: C,
57.04; H, 6.92. C15H22O5S requires C, 57.30;
H, 7.05).
D
[h]2D0 +10° (c 1, CHCl3); Rf 0.38 (solvent D,
1:4 EtOAc–PhCH3); (Anal. Found: C, 69.37;
H, 5.07. C61H52O17 requires C, 69.31; H, 4.96);
lH 2.53 (1 H, br s, OH), 2.92 (2 H, d, J5%6% 6.9,
H%-6a,b), 3.51 (1 H, br t, H%-5), 3.91 (1 H, dd,
J3%,4% 3.3, J2%,3% 10.0, 3%-H), 3.97 and 4.06 (AB-
system, Jgem 12.0, PhCH2), 4.16 (1 H, br d, J4,5
9.7, 5-H), 4.54 (2 H, br s, 6-Ha,b), 4.57 (1 H, t,
J3,4 9.7, 4-H), 4.75 (1 H, d, J1%,2% 7.8, 1%-H), 5.24
(1 H, dd, 2%-H), 5.46 (1 H, d, 4%-H), 5.75 (1 H,
dd, J1,2 1.8, J2,3 3.2, 2-H), 5.87 (1 H, dd, 3-H),
6.41 (1 H, d, 1-H) and 6.95–8.20 (35 H, m,
7×Ph).
Ethyl 2,4-di-O-benzoyl-6-O-benzyl-1-thio-
i- -galactopyranoside (10).—Solid; mp 107–
D
108 °C (4:1 hexane–EtOAc); [h]2D0 +9° (c 1,
CHCl3); Rf 0.56 (solvent B); (Anal. Found: C,
66.69; H, 5.79. C29H30O7S requires C, 66.65;
H, 5.79); lH 1.33 (3 H, t, J 7.4, SCH2CH3),
2.72–2.92 (3 H, m, SCH2CH3 and OH), 3.67
(2 H, m, 6-Ha and 6-Hb), 4.01 (1 H, br t,
J
5,6a=J5,6b 6.1, 5-H), 4.15 (1 H, m, 3-H), 4.45
and 4.55 (AB-system, Jgem 11.7, PhCH2), 4.72
(1 H, d, J1,2 9.9, 1-H), 5.42 (1 H, t, J2,3 9.9,
2-H), 5.78 (1 H, d, J3,4 2.8, 4-H) and 7.20–
8.30 (15 H, m, 3×Ph).
2,3,4,6-Tetra-O-acetyl-i-
osyl-(1“3)-2,4-di-O-benzoyl-6-O-benzyl-i-
- galactopyranosyl - (1“4) - 1,2,3,6 - tetra - O-
benzoyl-h- -mannopyranose (14).—Amor-
D
-galactopyran-
Ethyl
2,4-di-O-benzoyl-6-O-benzyl-3-O-
- galactopyranoside
D
chloroacetyl - 1 - thio - i -
D
D
(11).—Solid; mp 105–106 °C; [h]2D0 +60° (c 1,
CHCl3); Rf 0.59 (solvent C, 1:9 EtOAc–
PhCH3); (Anal. Found: C, 62.23; H, 5.21.
C31H31ClO8S requires C, 62.15; H, 5.22); lH
1.32 (3 H, t, J 7.4, SCH2CH3), 2.82 (2 H, m,
SCH2CH3), 3.60 (1 H, dd, J5,6a 7.3, J6a,6b 9.4,
6-Ha), 3.71 (1 H, dd, J5,6b 5.9, 6-Hb), 3.88 and
3.95 (AB-system, Jgem 15.2, ClCH2), 4.12 (1 H,
br t, 5-H), 4.42 and 4.54 (AB-system, Jgem
11.8, PhCH2), 4.75 (1 H, d, J1,2 9.9, 1-H), 5.45
(1 H, dd, J3,4 3.4, J2,3 9.9, 3-H), 5.63 (1 H, t,
2-H), 5.87 (1 H, d, 4-H) and 7.20–8.30 (15 H,
m, 3×Ph).
phous solid; [h]2D0 +23° (c 1, CHCl3); Rf 0.16
(solvent D); (Anal. Found: C, 64.71; H, 5.55.
C75H70O26 requires C, 64.93; H, 5.09); lH 1.36,
1.73, 1.88 and 1.90 (12 H, 4×s, 4×Ac), 2.95
(2 H, d, J5%,6% 6.3, 6%-Ha,b), 3.46 (1 H, br t,
5%-H), 3.64 (1 H, br t, J5%%,6%%a=J5%%,6%%b 6.6, 5%%-H),
3.85 (1 H, dd, J6%%a,6%%b 11.2, 6%%-Ha), 3.91 (1 H,
dd, J3%,4% 3.3, J2%,3% 10.0, 3%-H), 4.04 (1 H, dd,
6%%-Hb), 4.06 (2 H, m, PhCH2), 4.10 (1 H, m,
5-H), 4.41 (1 H, J5,6a 2.8, J6a,6b 11.2, 6-Ha),
4.41 (1 H, d, J1%%,2%% 7.8, 1%%-H), 4.51 (1 H, br d,
6-Hb), 4.54 (1 H, dd, J3%%,4%% 3.4, J2%%,3%% 10.4,
3%%-H), 4.60 (1 H, t, J3,4=J4,5=9.7, 4-H), 4.73
(1 H, d, J1%,2% 7.9, 1%-H), 4.82 (1 H, dd, 2%%-H),
5.10 (1 H, d, 4%%-H), 5.51 (1 H, br s, 4%-H), 5.51
(1 H, dd, 2%-H), 5.75 (1 H, dd, J1,2 1.7, J2,3 3.3,
2-H), 5.84 (1 H, dd, 3-H), 6.39 (1 H, d, 1-H)
and 6.85–8.10 (35 H, 7×Ph); lC (75 MHz ;
the same for the all 13C NMR data) 19.6, 20.3,
20.4 and 20.5 (4×Ac), 60.7 (C-6%%), 61.9 (C-6),
66.3 (C-4%%), 67.4 (C-6%), 68.2 (C-2%%), 69.4 (C-
2), 69.6 (C-4%), 71.8 (C-2%), 70.0 (C-3), 70.3
2,4-Di-O-benzoyl-6-O-benzyl-3-O-chloro-
acetyl-i-
D
-galactopyranosyl-(1“4)-1,2,3,6-
tetra-O-benzoyl-h-
D
-mannopyranose (12).—
Amorphous solid; [h]2D0 +37° (c 1, CHCl3); Rf
0.44 (solvent C); (Anal. Found: C, 66.98; H,
4.77. C63H53ClO18 requires C, 66.75; H, 4.71);
lH 2.91 (1 H, dd, J5%,6%a 5.4, J6%a,6%b 8.2, H%-6a),
3.00 (1 H, t, J5%,6%b 8.9, 6%-Hb), 3.55 (1 H, br dd,
H%-5), 3.68 and 3.77 (AB-system, Jgem 15.3,

D.V. Yashunsky et al. / Carbohydrate Research 336 (2001) 243–248
247
4.45–4.65 (7 H, m, 6-Hb, 6%%-Hab and 2×
PhCH2), 4.60 (1 H, t, J3,4=J4,5 9.6, 4-H), 4.70
(1 H, d, J1%,2% 7.9, 1%-H), 5.22 (1 H, d, 1%%%-H),
5.46 (1 H, dd, J2%,3% 9.9, 2%-H), 5.67 (1 H, d, J3%,4%
2.8, 4%-H), 5.77 (1 H, dd, J1,2 1.9, J2,3 3.2, 2-H),
5.81 (1 H, dd, 3-H), 6.36 (1 H, d, 1-H) and
6.80–8.00 (55 H, 11×Ph); lC 26.5 and 27.7
(Me2C), 59.6 (C-5%%%), 61.9 (C-6), 63.3 (C-6%%),
67.5 (C-6%), 69.4 (C-2), 70.1 (C-3), 70.5 (C-4%),
70.9 (C-5%%), 71.1 (CH2Ph), 71.8 (C-5), 72.2
(C-2%), 72.3(3) (C-4 and 2×CH2Ph), 73.1 (C-
5%), 73.2 (CH2Ph), 73.3 (C-4%%), 74.5 (C-4%%%),
74.8 (C-3%), 74.9 (C-2%%), 76.0 (C-2%%%), 77.2 (C-
3%%%), 79.7 (C-3%%), 91.1 (C-1), 96.1 (C-1%%%), 100.8
(C-1%%), 101.2 (C-1%), 110.3 (Me2C), 127.1–
138.8 (Ph) and 164.0–166.1 (CꢀO).
(C-5%%), 70.7 (C-3%%), 71.6 (C-5), 72.3 (C-4), 72.9
(C-5%),73.2 (CH2Ph), 77.0 (C-3%), 91.0 (C-1),
101.0 (C-1%and C-1%%), 127.6–(Ph) and 164.7–
170.2 (CꢀO).
6 - O - Benzoyl - 3,4 - O - isopropylidene - i -
galactopyranosyl-(1“3)-2,4-di-O-benzoyl-6-
O - benzyl - i - - galactopyranosyl - (1“4)-
1,2,3,6-tetra-O-benzoyl-h- -mannopyranose
D
-
D
D
(18).—Amorphous solid; [h]2D0 +33° (c 1,
CHCl3); Rf 0.41 (solvent B); (Anal. Found: C,
68.13; H, 5.46. C77H70O23 requires C, 67.83; H,
5.18); lH 1.14 and 1.27 (6 H, 2×s, Me2C),
2.36 (1 H, br s, OH), 2.92 (2 H, d, J5%,6% 5.6,
6%-Ha,b), 3.21 (1 H, t, J1%%,2%%=J2%%,3%% 7.5, 2%%-H),
3.49 (1 H, br t, 5%-H), 3.65 (1 H, dd, J3%%,4%% 5.6,
3%%-H), 3.84 (1 H, m, 5%%-H), 3.88 (1 H, dd, J3%.4%
3.2, J2%,3% 10.0, 3%-H), 3.95 (1 H, dd, J4%%,5%% 1.9,
4%%-H), 4.01 (1 H, d, 1%%-H), 4.02 (2 H, m,
PhCH2), 4.15 (1 H, br d, J4,5 9.6, 5-H), 4.41 (2
H, m, 6%%-Ha,b), 4.47 (1 H, dd, J5,6a 2.3, J6a,6b
12.1, 6-Ha), 4.58 (1 H, br d, 6-Hb), 4.63 (1 H,
t, J3,4=J4,5 =9.8, 4-H), 4.78 (1 H, d, J1%,2% 7.9,
1%-H), 5.48 (1 H, dd, 2%-H), 5.58 (1 H, d, 4%-H),
5.78 (1 H, dd, J1,2 1.5, J2,3 3.3, 2-H), 5.85 (1 H,
dd, 3-H), 6.40 (1 H, d, 1-H) and 6.80–8.10 (40
H, 8×Ph); lC 26.1 and 27.8 (Me2C), 61.9
(C-6), 63.1 (C-6%%), 67.4 (C-6%), 69.5 (C-2), 69.9
(C-3), 70.0 (C-4%), (C-70.9 (C-5%%), 71.8 (C-5),
72.1 (C-2%), 72.3 (C-4), 72.5 (C-2%%), 72.8 (C-
4%%), 73.0 (C-5%), 73.2 (CH2Ph), 77.8 (C-3%),
78.0 (C-3%%), 91.1 (C-1), 100.8 (C-1%), 103.2
(C-1%%), 110.1 (Me2C) 125.0–137.4 (Ph) and
163.9–166.0 (CꢀO).
2,3,4-Tri-O-benzoyl-i-
(1“2)-3,4,6-tri-O-benzoyl-i-
osyl - (1“3)-2,4-di-O-benzoyl-6-O-(p,p%-dime-
thoxytrityl) - i - - galactopyranosyl - (1“4)-
1,2,3,6-tetra-O-benzoyl-h- -mannopyranose
D
-arabinopyranosyl-
D
-galactopyran-
D
D
(5).—Amorphous solid; [h]2D0 +22° (c 1,
CHCl3); Rf 0.66 (solvent D); (Anal. Found: C,
69.96; H, 4.92. C128H106O34 requires C, 70.26;
H, 4.88); lH 2.50 (1 H, br d, J5%%%a,5%%%b 12.2,
5%%%-Ha),3.17 (1 H, br t, J5%,6%=J6%a,6%b 8.9, 6%-Ha),
3.28 (1 H, dd, J5%,6%b 5.4, 6%-Hb), 3.51 and 3.57
(2×3 H, 2×s, 2×OMe), 3.81 (1 H, dd,
5%-H), 4.14–4.23 (3 H, m, 2%%-H, 5-H, 5%%-H),
4.36 (1 H, br d, 5%%%-Hb), 4.38 (1 H m, 6-Ha),
4.39 (1 H, dd, J2%,3% 9.8, J3%,4% 3.4, 3%-H), 4.64 (2
H, m, 6%%-Ha,b), 4.68 (1 H, t, J3,4=J4,5 10.0,
4-H), 4.75 (1 H, d, J1%%,2%% 7.4, 1%%-H), 4.84 (1 H,
dd, J5,6 5.7, J6a,6b 10.9, 6-Hb), 4.89 (1 H, d,
J1%,2% 7.9, 1%-H), 5.05 (1 H, dd, J3%%,4%% 2.9, J2%%,3%%
10.4, 3%%-H), 5.26 (1 H, d, J1%%%,2%%% 4.0, 1%%%-H),
5.42 (1 H, dd, J2%%%,3%%% 10.6, 2%%%-H), 5.57–5.65 (2
H, m, 2%-H, 4%%%-H), 5.70 (1 H, dd, J3%%%,4%%% 3.5,
3%%%-H), 5.78 (1 H, d, 4%%-H), 5.82–5.87 (2 H, m,
2-H, 3-H), 6.18 (1 H, d, 4%-H), 6.50 (1 H, d,
J1,2 1.6, 1-H) and 6.52–8.40 (73 H, 12×Bz
and DMT); lC 54.9 and 55.0 (2×Me), 59.3
(C-6%), 60.6 (C-5%%%), 61.1 (C-6), 62.2 (C-6%%),
67.4 (C-4%%), 67.7 (C-3%%%), 68.1 (C-2%%%), 69.7
(C-2), 69.9(2) (C-3 and C-4%), 70.2 (C-4%%%), 70.7
(C-5%%), 71.9 (C-2%), 72.1(2) (C-4 and C-5), 72.6
(C-5%), 73.0 (C-2%%), 74.2 (C-3%%), 74.7 (C-3%),
2,3,4-Tri-O-benzyl-i-
“2)-6-O-benzoyl-3,4-O-isopropylidene-i-
galactopyranosyl-(1“3)-2,4-di-O-benzoyl-6-
O - benzyl - i - - galactopyranosyl - (1“4)-
1,2,3,6-tetra-O-benzoyl-h- -mannopyranose
D
-arabinopyranosyl-(1
D
-
D
D
(22).—Amorphous solid; [h]2D0 −5° (c 1,
CHCl3); Rf 0.59 (solvent D); (Anal. Found: C,
69.97; H, 5.54. C103H96O27 requires C, 70.06;
H, 5.48); lH 1.18 and 1.32 (6 H, 2×s, Me2C),
2.60 (1 H, br d, J5%%%,5%%%b 11.5, 5%%%-Ha), 3.04 (2 H,
br d, J5%,6% 6.1, 6%-Ha,b), 3.43–3.58 (4 H, m,
4%%%-H, 5%-H, 2%%-H, 5%%%-Hb), 3.64 (1 H, dd, J2%%%,3%%%
10.2, J3%%%,4%%% 2.8, 3%%%-H), 3.73 (1 H, dd, J1%%%,2%%%
3.4, 2%%%-H), 3.80–3.90 (2 H, m, 3%%-H and
5%%-H), 3.96 (1 H, dd, J3%%,4%% 5.4, J4%%,5%% 1.9, 4%%-H),
3.97–4.12 (4 H, m, 3%-H, 5-H and PhCH2),
4.23–4.37 (4 H, m, 1%%-H, 6-Ha and PhCH2),
86.1 (Ph*C), 91.0 (C-1), 97.3 (C-1%%%), 100.8
3
(C-1%%), 101.3 (C-1%), 112.9–136.0 (Ph) and
164.0–166.0 (CꢀO).

248
D.V. Yashunsky et al. / Carbohydrate Research 336 (2001) 243–248
6. (a) Nikolaev, A. V.; Watt, G. M.; Ferguson, M. A. J.;
Brimacombe, J. S. J. Chem. Soc., Perkin Trans. 1 1997,
969–979;
(b) Higson, A. P.; Tsvetkov, Y. E.; Ferguson, M. A. J.;
Nikolaev, A. V. Tetrahedron Lett. 1999, 40, 9281–9284.
7. (a) Preliminary experiments (Watt, G. M. Ph.D. Thesis,
University of Dundee, 1996, p. 63–67) indicated that the
glycosylation reaction between 2,4,6-tri-O-benzoyl-3-O-
i-
topyranosyl-(1“3)-i-
“4)-h- -mannopyranose (1).—Amorphous
D
-Arabinopyranosyl-(1“2)-i-
D
-galac-
D
-galactopyranosyl-(1
D
solid; [h]2D0 −26° (c 1, water); lH (D2O) (inter
alia) 3.52 (1 H, br d, J5%%%a,5%%%b 12.7, 5%%%-Ha), 4.09
(1 H, d, J3%,4% 3.0, 4%-H), 4.28 (1 H, br d,
5%%%-Hb), 4.38 (1 H, d, J1%,2% 7.7, 1%-H), 4.65 (1 H,
d, J1%,2% 7.7, 1%%-H), 5.09 (1 H, s, 1-H), 5.26 (1
H, d, J1%%%,2%%% 3.2, 1%%%-H); lC (D2O) 61.41 (C-6),
61.96 (C-6%%), 62.17 (C-6%), 64.38 (C-5%%), 69.67,
69.76, 69.88, 69.94 and 70.02 (C-2%%%, C-3, C-
3%%%, C-4%and C-4%%), 70.02 (C-4%%%), 71.25 (C-2%),
71.45 (C-2), 72.13 (C-5), 74.52 (C-3%%), 75.96
(C-5%%), 76.07 (C-5%), 77.14 (C-4), 77.91 (C-2%%),
81.94 (C-3%), 94.86 (C-1), 100.76 (C-1%%%),
103.79 (C-1%%) and 103.90 (C-1%); b anomer
components: 71.70 (C-2), 72.82 (C-3), 76.74
(C-5) and 94.68 (C-1); ES-MS(+): m/z 242.62
(100%, [M+4Na−H]3+ (expected m/z,
242.40. C23H40O20 requires M, 636.21).
benzyl-b-
O-chloroacetyl-a-
date (analogue of B–C block) and methyl 2,3,6-tri-O-
D
-galactopyranosyl-(1“3)-2,4-di-O-benzoyl-6-
D
-galactopyranosyl trichloroacetimi-
benzoyl-a-D-mannopyranoside (analogue of the A unit)
was inefficient;
(b) All attempts to realise the (2+2) (i.e., C–D+A–B)
synthetic scheme using the condensation of 2,3,4-tri-O-
benzoyl-b-
D-arabinopyranosyl-(1“2)-3,4,6-tri-O-ben-
zoyl-a- -galactopyranosyl trichloroacetimidate (as the
D
C–D unit) and 2-O-benzoyl-4,6-O-benzylidene-b-
galactopyranosyl-(1“4)-1,2,3,6-tetra-O-benzoyl-a-
D
-
-
D
mannopyranose (as the A–B unit) in propionitrile in the
presence of TMSOTf failed providing stereospecifically
the corresponding b,a,b-linked tetrasaccharide (64%;
J1%%,2%% 3.4 Hz).
8. Sato, S.; Ito, Y.; Ogawa, T. Carbohydr. Res. 1986, 155,
C1–C5.
9. Novel compounds 1, 5, 7, 8–14, 18 and 22 showed
satisfactory spectral and analytical (or ES–MS, for com-
pound 1) data (see Appendix A).
10. (a) Qiao, L.; Vederas, J. C. Org. Chem. 1993, 58, 3480–
3482;
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