Synthesis of chacotriose analogues

Article abstract of DOI:10.1016/j.carres.2004.03.020

We report here the synthesis of three chacotriose analogues, namely β-L-fucopyranosyl-(1→2)-[β-L-fucopyranosyl-(1→4)] -D-glucopyranose, β-L-fucopyranosyl-(1→2)-[β-L-fucopyranosyl- (1→4)]-D-galactopyranose, and α-L-rhamnopyranosyl-(1→2)- [α-L-rhamnopyranos

Full text of DOI:10.1016/j.carres.2004.03.020

Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 1511–1516
Synthesis of chacotriose analogues
a
c
a
Vincent Lequart,a,b Gerard Goethals, Alfredo Usubillaga, Pierre Villa,
ꢀ
b
Romeo Cecchelli and Patrick Martin
b,
*
ꢀ
aLaboratoire des Glucides, Universitꢀe de Picardie Jules Verne, 33 rue Saint-Leu, F-80039 Amiens, France
bLaboratoire de la Barriꢁere Hꢀemato-encꢀephalique, Unitꢀe mixte Institut Pasteur de Lille-Universitꢀe d’Artois,
Facultꢀe des Sciences Jean Perrin, rue Jean Souvraz SP 18, F-62307 Lens, France
cInstituto de Investigaciones, Facultad de Farmacia, Universidad de Los Andes, Merida 5101, Venezuela
Received 15 December 2003; accepted 16 March 2004
Abstract—We report here the synthesis of three chacotriose analogues, namely b-
(1 fi 4)]- -glucopyranose, b- -fucopyranosyl-(1 fi 2)-[b- -fucopyranosyl-(1 fi 4)]- -galactopyranose, and a-
(1 fi 2)-[a- -rhamnopyranosyl-(1 fi 4)]-a- -galactopyranose.
Ó 2004 Elsevier Ltd. All rights reserved.
L
-fucopyranosyl-(1 fi 2)-[b-
L-fucopyranosyl-
-rhamnopyranosyl-
D
L
L
D
L
L
D
Keywords: Oligosaccharides; Chacotriose analogues; Trichloroacetimidate method
1. Introduction
The role of the glycon part is often limited to improve
the biological effect of the active form, without any
specificity for any particular organ. Kuo and co-
workers,5 for example, reported that the chacotriosyl
moiety of solamargine plays a crucial role in triggering
cell death by apoptosis. However, some monosaccha-
The large family of saponins has received considerable
attention because of their varied pharmaceutical prop-
erties.1 Since ancient times, plant extract containing
saponins have been used in traditional (indigeneous)
medicine. Among the large number of glycoconjugates,
we have been interested in the steroidal glycoalkaloids2
isolated from Solanum plants. Most Solanum species
contain a major steroidal glycoalkaloid with the agly-
rides, such as
receptors on a given organ and play a important role
in the body.6
-fucose and -galactose are important
recognition component of cell-surface glycans. A num-
ber of -fucose or -galactose-containing glycoconju-
L-fucose or D-galactose, have specific
L
D
cone bound to chacotriose, a-
L
-rhamnopyranosyl-
-glucopyranose.
L
D
(1 fi 2)-[a- -rhamnopyranosyl-(1 fi 4)]-
L
D
gates have been reported to be involved in a variety of
biological functions, such as growth regulation, receptor
function, cell–cell interaction, and antigenicity.7 They
play a role in the inflammation process8 as a component
of sialyl LewisX.9
Chacotriose, in particular, is present in solamargine and
chaconine. In these two cases, it is associated at the
anomeric position by the steroidal alkaloids solasodine
or solanidine. There are also oligosaccharidic counter-
parts to chacotriose, in particular solatriose, a-
rhamnopyranosyl-(1 fi 2)-[b- -glucopyranosyl-(1 fi 3)]-
-galactopyranose. These steroids present many prop-
erties.3 However glycosides-containing chacotriose are
consistently more active than their solatriose-containing
counterparts.4
L
-
The biological effects of the steroids and their low
availability from natural sources, make them an
important synthetic target. Thus much research was
thus directed toward the chemical synthesis of chaco-
triose and analogues.10–14 We have recently published a
paper on the peracetylated chacotriose.14 We report here
strategies to obtain some chacotriose analogues. Spe-
D
D
cifically We have replaced the central
a
D
-glucose unit by
-fucose.
*Corresponding author. Tel.: +33-3-2179173; fax: +33-3-21791736;
e-mail: patrick.martin@univ-artois.fr
D
-galactose unit, or the L-rhamnose units by L
0008-6215/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.03.020

1512
V. Lequart et al. / Carbohydrate Research 339 (2004) 1511–1516
2
OR
2. Results and discussion
HO
O
O
1
3
1
OR
OR
OR
1
2
1
OR
2
Chacotriose, is the glucidic moiety of the saponins sol-
amargine and chaconine. It has a central D-glucose
unit joined at O-2 and O-4 by two L-rhamnose units.
The glycosteroids and difficulty to obtain in quantity.
For the present quest we describe the synthesis of
R
R
O
O
OR
OH
R1
R1
R2
R3
R2
H
Piv
-CMe2-
-CMe2-
H
Bn
Bn
Bn
5
6
7
8
α β, 4:1
/
α
/β, 1:0
Scheme 2.
three chacotriose analogues: b-
(1 fi 2)-[b- -fucopyranosyl-(1 fi 4)]- -galactopyranose,
b- -fucopyranosyl-(1 fi 2)-[b- -fucopyranosyl-(1 fi 4)]-
-galactopyranose, and a- -rhamnopyranosyl-(1 fi 2)-
[a- -rhamnopyranosyl-(1 fi 4)]-a- -galactopyranose.
L-fucopyranosyl-
L
D
mixture 7a=7b (a=b, 4:1) was separated by conventional
work up: acetylation following by deacetylation. Position
6 of 7a was selectively protected with pivaloyl chloride18
in pyridine to give benzyl 3-O-benzyl-6-O-pivaloyl-a-
galactopyranoside (8) in 76% yield (Scheme 2).
The 2-OH and 4-OH groups of the D-glucose or
galactose acceptors 4 or 8 were glycosylated with the
trichloroacetimidate donors 920 or 1021 by using boron
trifluoride etherate (BF3ÆEt2O)22 as promoter to give the
fully protected chacotrioside analogues 11a, 12a, and
13a (Table 1) (Scheme 3).
L
L
D
L
L
D
D
-
The strategy adopted was to protect the glucose unit
partially leaving only the 2-OH and 4-OH groups avail-
able for glycosidic bond formation with two L-rhamno-
pyranose or L-fucopyranose units. For this purpose,
three steps were required, using selective pivaloylation.
Compound 4 was readily prepared in large amount (20-
D
-
g scale) starting from 1,2:5,6-di-O-isopropylidene-a-D-
glucofuranose (1).15 Compound 2 was prepared by con-
densing 1 with benzyl bromide16 in 83% yield. Removing
the isopropylidene protection by 3:2 HOAc–H2O fol-
lowed by selective protection of the anomeric hydroxyl
with benzyl alcohol in the presence of acetyl chloride17
afforded compound 3 (71% yield, a=b, 3:1) (Scheme 1).
The anomeric mixture 3a=3b was separated by crys-
tallization with ether–EtOAc. Position 6 of 3a was then
selectively protected with pivaloyl chloride18 in pyridine
However, if the glycosyl donor is L-fucose (entry 1)
the yield of trisaccharide becomes lower. To overcome
this disadvantage, we used the ‘inverse procedure’ (IP)
described by Schmidt and Kinzy22 in which the hydroxyl
groups of the acceptor (4) are activated with BF3ÆEt2O
before addition of the donor. Under these conditions
(entry 2) the yield was increased to a significant degree
(61% yield). This improved yield was also observed in
entries 3 and 4. The yield is thus increased by 31%.
to give benzyl 3-O-benzyl-6-O-pivaloyl-a-
anoside (4) in 82% yield.
By the same method, we also prepared the galactosy-
D-glucopyr-
However when the donor is L-rhamnose, the glycosyl-
ation yield was best by even the ‘normal procedure’.
Trisaccharides 11a, 12a, and 13a were then peracetyl-
ated by a similar sequence. The protected trisaccharides
were treated with hydrogen in the presence of Pd/C
(10%) to give 11b–13b and, then with NaOH to remove
the pivaloyl and acetyl groups, and were subsequently
acetylated to obtain the desired peracetylated chacotri-
ose analogues 11c, 12c, and 13c.
lated acceptor 8, starting from 1,2:5,6-di-O-isopropyl-
idene-a-D
-galactofuranose (5).19 Removing the iso-
propylidene protection of 6 with 3:2 HOAc–H2O
followed by selective protection of the anomeric hydroxyl
with benzyl alcohol in the presence of acetyl chloride17
afforded compound 7 (65% yield, a=b, 4:1). The anomeric
1
2
2
R
R
O
O
OR
3. Experimental
O
O
1
3
1
OR
OR
OR
1
OR
2
HO
3.1. General methods
OR
OH
R1
Bn
R1
R2
R3
H
Bn
R2
H
Piv
-CMe2-
-CMe2-
1
2
3
4
α/β, 3:1
α/β, 1:0
Melting points were determined on an electrothermal
automatic apparatus, and are uncorrected. Optical
rotations for solutions in CHCl3 were measured at 25 °C
Bn
Scheme 1.
Table 1. Glycosylation of compound 4 and 8
Entries
Conditions
Acceptor
Donor
Product
Yield (%)
1
2
3
4
5
6
NP (4/9 ¼ 1:3)
IP (4/9 ¼ 1:3)
NP (8/9 ¼ 1:3)
IP (8/9 ¼ 1:3)
NP (8/10 ¼ 1:3)
IP (8/10 ¼ 1:3)
4
4
8
8
8
8
9
11a
11a
12a
12a
13a
13a
30
61
35
66
68
74
9
9
9
10
10
NP, normal procedure; IP inverse procedure.

V. Lequart et al. / Carbohydrate Research 339 (2004) 1511–1516
1513
OC(NH)CCl
AcO
OC(NH)CCl
O
3
O
3
CH
CH
3
3
AcO
AcO
OAc
OAc
AcO
9
10
2
2
OR
O
OR
3
CH
R O
O
3
2
O
O
O
OR
3
CH
3
R O
1
3
1
O
O
OR
R O
OR
3
3
1
3
OR
1
OR
3
1
OR
O
OR
OR
3
3
3
CH
OR
3
R
O
1
3
OR
3
R O
O
3
OR
O
O
R
O
O
CH
O
3
R O
O
3
OR
CH
O
CH
3
R
O
R O
3
3
OR
3
3
OR
R O
OR
11a: R1=Bn, R2=Piv, R3=Ac
11b: R1=H, R2=Piv, R3=Ac
11c: R1=R2=R3=Ac
12a: R1=Bn, R2=Piv, R3=Ac
12b: R1=H, R2=Piv, R3=Ac
12c: R1=R2=R3=Ac
13a: R1=Bn, R2=Piv, R3=Ac
13b: R1=H, R2=Piv, R3=Ac
13c: R1=R2=R3=Ac
Scheme 3.
with a Jasco digital polarimeter model DIP-370 using a
sodium lamp. NMR spectra were recorded with a Bru-
ker WB-300 instrument for solutions in CDCl3 (internal
9.2 Hz, H-4), 3.35 (m, 1H, J5;6a 4.7 Hz, J5;6b 3.4 Hz, H-5);
13C NMR (CDCl3, 75.5 MHz): d 138.0–128.0 (Ph), 100.4
(C-1), 82.9 (C-3), 75.7 (C-5), 74.9 (CH2–Ph), 73.3 (C-2),
71.2 (CH2–Ph), 70.8 (C-4), 62.3 (C-6). Anal. Calcd for
C20H24O6: C, 66.65; H, 6.71. Found: C, 66.71; H 6.78.
1
Me4Si). All compounds were characterized by H, 13C,
1
1
DEPT, H–1H COSY, and H–13C experiments. Reac-
tions were monitored by high-performance liquid chro-
matography (HPLC) (Waters 721) using a reverse-phase
column RP-18 (E. Merck). Analytical thin-layer chro-
matography (TLC) was performed on E. Merck alumi-
num-backed silica gel (Silica Gel F254). Column
chromatography was performed on silica gel (60 mesh,
Matrex) by gradient elution with hexane–acetone or
hexane–EtOAc (in each case the ratio of silica gel to
product mixture to be purified was 30:1).
3.3. Benzyl 3-O-benzyl-6-O-pivaloyl-a-D-glucopyranoside
(4)
To a solution of 3a (20 g, 55 mmol) in pyridine (200 mL),
pivaloyl chloride (10.2 mL, 82 mmol) was slowly added
at 0 °C. After being stirred for 2 h, the mixture was
diluted with EtOAc, and washed with 20% aq HCl, satd
aq NaHCO3, and then brine. The organic phase was
dried over anhydrous Na2SO4 and concentrated under
reduced pressure. Chromatography of the residue on a
silica gel column (9:1 hexane–EtOAc) gave 4 as an oil in
3.2. Benzyl 3-O-benzyl-D-glucopyranoside (3)
A suspension of diacetal derivative 216 (60 g, 171 mmol)
in 60% aq HOAc was stirred for 12 h, at 90 °C. The
solvent (aq HOAc) was removed by coevaporation with
toluene (500 mL). The residue was dissolved in benzyl
alcohol (200 mL) and acetyl chloride (27 mL) was added
at 0 °C. After 24 h at rt, the mixture was neutralized with
solid NaHCO3, filtered, and concentrated under reduced
pressure. Chromatography of the residue on a silica gel
column (7:3 hexane–acetone) gave 3 in 71% yield (a=b,
71% yield; ½aŠ )47.1 (c 1.1, CHCl3); 1H NMR (CDCl3,
D
300 MHz): d 7.36–7.28 (Ph), 4.94 (d, 1H, J1;2 3.6 Hz, H-
1), 4.91, 4.73 (2d, 2H, CH2–Ph), 4.82, 4.65 (2d, 2H,
CH2–Ph), 4.43 (dd, 1H, J6a;6b 12.0 Hz, H-6a), 4.38 (dd,
1H, H-6b), 3.71 (dd, 1H, J2;3 9.0 Hz, H-2), 3.55 (m, 1H,
J3;4 8.7 Hz, H-3), 3.48 (m, 2H, J5;6a 4.5 Hz, J5;6b 2.5 Hz,
H-5, H-4), 1.24 (s, 9H, CMe3); 13C NMR (CDCl3,
75.5 MHz): d 169.9 (CO), 138.5–128.1 (Ph), 97.5 (C-1),
82.6 (C-3), 75.0 (CH2–Ph), 73.2 (C-2), 70.6 (C-4), 70.5
(CH2–Ph), 70.2 (C-5), 63.4 (C-6), 39.4 (CMe3), 27.6
(CMe3). Anal. Calcd for C24H32O7: C, 67.57; H, 7.21.
Found: C, 67.63; H 7.25.
3:1); anomer 3a, oil, ½aŠ +75.5 (c 1.0, CHCl3); 1H NMR
D
(CDCl3, 300 MHz): d 7.38–7.28 (Ph), 5.01, 4.74 (2d, 2H,
CH2–Ph), 4.97 (d, 1H, J1;2 3.2 Hz, H-1), 4.76, 4.55 (2d,
2H, CH2–Ph), 3.78 (d, 1H, J5;6 3.8 Hz, H-6a), 3.67 (m,
2H, H-2, H-5), 3.61 (m, 2H, H-3, H-4); 13C NMR
(CDCl3, 75.5 MHz): d 137.3–128.3 (Ph), 98.4 (C-1), 83.3
(C-3), 75.4 (CH2–Ph), 73.2 (C-2), 71.8 (C-4), 70.5 (C-5),
70.3 (CH2–Ph), 62.6 (C-6); anomer 3b, white crystals, mp
102–107 °C; ½aŠD )45.3 (c 1.1, CHCl3); 1H NMR (CDCl3,
300 MHz): d 7.37–7.27 (Ph), 5.03 (dd, 1H, J2;3 9.5 Hz, H-
2), 4.86, 4.62 (2d, 2H, JHa;Hb 12.4 Hz, CH2–Ph), 4.72, 4.69
(2d, 2H, JHa;Hb 11.3 Hz, CH2–Ph), 4.48 (d, 1H, J1;2 8.0 Hz,
H-1), 3.90 (dd, 1H, J6a;6b 11.9 Hz, H-6a), 3.80 (dd, 1H, H-
6b), 3.72 (dd, 1H, J3;4 9.3 Hz, H-3), 3.55 (dd, 1H, J4;5
3.4. Benzyl 3-O-benzyl-a-D-galactopyranoside (7)
A procedure similar to that for the preparation of 3 was
employed. A suspension of diacetal derivative 619 (30 g,
95 mmol) in 60% aq HOAc was stirred at 90 °C for 12 h.
The solvent was removed by coevaporation with toluene
(250 mL). The residue was dissolved in benzyl alcohol
(100 mL) and acetyl chloride (13.5 mL) was added at
0 °C. After 24 h at rt, the mixture was neutralized with
solid NaHCO3, filtered, and concentrated under reduced

1514
V. Lequart et al. / Carbohydrate Research 339 (2004) 1511–1516
pressure. Chromatography of the residue on a silica gel
column (6:4 hexane–acetone) gave 7 as an oil in 65% yield
(a=b, 4:1). A sole anomer (a) was obtained by acetylation;
anomer 7a white crystals, mp 75–78 °C; ½aŠD )29.0 (c 1.0,
CHCl3); 13C NMR (CDCl3, 75.5 MHz): d 139.1–128.6
(Ph), 99.0 (C-1), 77.2 (C-3), 75.4 (C-4), 72.8, 70.6 (CH2–
Ph), 68.4 (C-2), 63.7 (C-5), 62.5 (C-6). Anal. Calcd for
C20H24O6: C, 66.65; H, 6.71. Found: C, 66.68; H 6.74.
CHCl3); 13C NMR (CDCl3, 75.5 MHz): d glucose 169.8
(CO), 137.9–128.26 (Ph), 99.1 (C-1), 83.6 (C-3), 78.6 (C-
2), 75.2 (C-4), 75.8, 70.3 (CH2–Ph), 73.1 (C-5), 63.7 (C-
6), 39.1 (CMe3), 27.7 (CMe3), fucose (1 fi 4) 171.2–170.0
(CH3CO), 100.5 (C-1), 71.7 (C-3), 70.6 (C-4), 69.9–69.6
(C-2, C-5), 21.0–21.2 (CH3CO), 16.2 (C-6), fucose
(1 fi 2) 101.6 (C-1), 71.5 (C-3), 71.0 (C-4), 69.9–69.6 (C-
2, C-5), 16.3 (C-6). Anal. Calcd for C49H64O21: C, 59.51;
H, 6.52. Found: C, 59.48; H, 6.50.
3.5. Benzyl 3-O-benzyl-6-O-pivaloyl-a-D-galactopyrano-
side (8)
3.7. 2,3,4-Tri-O-acetyl-b-
tri-O-acetyl-b- -fucopyranosyl-(1 fi 4)]-1,3,6-tri-O-acet-
yl- -glucopyranose (11c)
L
-fucopyranosyl-(1 fi 2)-[2,3,4-
L
To a solution of 7a (20 g, 55 mmol) in pyridine (250 mL)
was slowly added pivaloyl chloride (10.2 mL, 82 mmol)
at 0 °C. After being stirred for 2 h, the mixture was
diluted with EtOAc, and washed with 20% aq HCl, satd
aq NaHCO3, and then brine. The organic phase was
dried over anhydrous Na2SO4 and concentrated under
reduced pressure. Chromatography of the residue on a
silica gel column (9:1 hexane–EtOAc) gave 8 as an oil in
D
A mixture of prehydrogenated 10% Pd–C catalyst
(50 mg) and 11a (250 mg, 0.25 mmol) dissolved in 1:1
MeOH–dioxane (10 mL) was shaked in a hydrogen
atmosphere (1 atm) during 12 h at 50 °C. The catalyst
was filtered off and concentrated under reduced pressure
to give an oil. A solution of the crude and NaOH
(150 mg, 3.1 mmol) dissolved in 1:1:1 H2O–MeOH–THF
(15 mL) was stirred at 40 °C for 2 h, then neutralized
with Dowex-50 (Hþ form), filtered, and concentrated.
The mixture (11b) was dissolved in pyridine (10 mL) and
added Ac2O (1 mL). After 24 h at 5 °C, the solution was
concentrated, diluted with EtOAc, and washed with 20%
aq HCl, satd aq NaHCO3, and then brine. The organic
phase was dried over anhydrous Na2SO4 and evapo-
rated under reduced pressure. Chromatography of the
residue on a silica gel column (9:1 hexane–EtOAc) gave
76% yield; ½aŠ )69.5 (c 1.0, CHCl3); 1H NMR (CDCl3,
D
300 MHz): d 7.53–7.28 (Ph), 5.20 (d, 1H, J1;2 3.8 Hz, H-
1), 4.78–4.49 (m, 4H, CH2–Ph), 4.25 (dd, 1H, J2;3
10.0 Hz, H-2), 4.22 (dd, 1H, J4;5 3.8 Hz, H-4), 4.20, 3.98
(m, 2H, J6a;6b 9.6 Hz, m, H-6), 3.85 (dd, 1H, J3;4 3.4 Hz,
H-3), 3.65 (m, 1H, J5;6a 1.8 Hz, J5;6b 4.5 Hz, H-5), 1.24 (s,
9H, CMe3); 13C NMR (CDCl3, 75.5 MHz): d 169.9
(CO), 139.1–128.6 (Ph), 98.9 (C-1), 77.1 (C-3), 74.6 (C-
4), 71.9, 70.6 (CH2–Ph), 68.4 (C-2), 63.5 (C-5), 63.1 (C-
6), 37.2 (CMe3), 27.6 (CMe3). Anal. Calcd for C24H32O7:
C, 67.57; H, 7.21. Found: C, 67.61; H 7.24.
11c as a white solid in 46% yield; mp 85–86 °C; ½aŠ
D
+26.1 (c 0.4, CHCl3); 13C NMR (CDCl3, 75.5 MHz): d
glucose 171.5–169.0 (CH3CO), 89.9 (C-1), 77.4 (C-4),
76.9 (C-2), 72.3 (C-3), 70.3 (C-5), 61.9 (C-6), 21.3–21.0
(CH3CO), fucose (1 fi 4) 99.9 (C-1), 71.5 (C-3), 71.3
(C-4), 69.9 (C-2), 69.3 (C-5), 16.5 (C-6), fucose (1 fi 2)
100.3 (C-1), 71.3 (C-3), 71.0 (C-4), 69.9 (C-2), 69.4 (C-5),
16.4 (C-6). Anal. Calcd for C36H50O23: C, 50.82; H, 5.92.
Found: C, 50.77; H, 5.89.
3.6. Benzyl 2,3,4-tri-O-acetyl-b-
[2,3,4-tri-O-acetyl-b- -fucopyranosyl-(1 fi 4)]-3-O-benz-
yl-6-O-pivaloyl-a- -glucopyranoside (11a)
L
-fucopyranosyl-(1 fi 2)-
L
D
Procedure 1: To a suspension of 4 (250 mg, 0.56 mmol),
916 (740 mg, 1.7 mmol) and 4 A MS (500 mg) in dry
ꢂ
CH2Cl2 (5 mL) at )60 °C under N2 was added a solution
of BF3ÆEt2O (3.2 · 10À2 mL, 0.28 mmol) in CH2Cl2.
After being stirred for 2 h at rt, the reaction was quen-
ched with Et3N, filtered, and concentrated. Chroma-
tography of the residue on a silica gel column (3:1
hexane–EtOAc) gave 11a as a white solid in 30% yield;
Procedure 2: To a stirred suspension of 4 (250 mg,
3.8. Benzyl-2,3,4-tri-O-acetyl-b-
[2,3,4-tri-O-acetyl-b- -fucopyranosyl-(1 fi 4)]-3-O-benz-
yl-6-O-pivaloyl-a- -galactopyranoside (12a)
L
-fucopyranosyl-(1 fi 2)-
L
D
A procedure similar to that for the preparation of 11a
was employed. Treatment of 8 (250 mg, 0.56 mmol) and
916 (740 mg, 1.7 mmol) with BF3ÆEt2O (3.2 · 10À2 mL,
0.28 mmol) gave 12a as a white solid in 35% (procedure
1) or 66% yield if we use the ‘inverse procedure’ (proce-
ꢂ
0.56 mmol) and 4 A MS (500 mg) in dry CH2Cl2 (5 mL)
at )60 °C under N2, was added a solution of BF3ÆEt2O
(32 lL in CH2Cl2, 0.28 mmol) followed by a solution of
9 (740 mg, 1.7 mmol) in CH2Cl2 (2 mL). The reaction
was allowed to warm to rt, and stirred for 2 h, and then
quenched by addition of NEt3. The mixture was diluted
with CH2Cl2 (20 mL), filtered, and concentrated under
reduced pressure. Chromatography of the residue on a
silica gel column (3:1 hexane–EtOAc) gave 11a as a
dure 2); mp 88–89 °C; ½aŠ )25.4 (c 0.2, CHCl3); 13C
D
NMR (CDCl3, 75.5 MHz): d galactose 171.1–170.3
(CO), 138.7–128.1 (Ph), 96.6 (C-1), 77.3 (C-3), 75.7
(C-4), 73.2, 68.3 (CH2–Ph), 68.2, 68.0 (C-2, C-5), 63.9
(C-6), 39.2 (CMe3), 27.6 (CMe3), fucose (1 fi 4) 99.3 (C-
1), 71.1 (C-4), 70.6 (C-3), 69.5 (C-2), 69.1 (C-5), 21.3
white solid in 61% yield; mp 55–57 °C; ½aŠ +2.6 (c 0.5,
D

V. Lequart et al. / Carbohydrate Research 339 (2004) 1511–1516
1515
(CH3CO), 16.6 (C-6), fucose (1 fi 2) 99.9 (C-1), 71.4 (C-
3.11. 2,3,4-Tri-O-acetyl-a-
[2,3,4-tri-O-acetyl-a- -rhamnopyranosyl-(1 fi 4)]-1,3,6-
tri-O-acetyl-a- -galactopyranose (13c)
L
-rhamnopyranosyl-(1 fi 2)-
4), 70.1 (C-3), 69.7 (C-2), 69.1 (C-5), 16.6 (C-6). Anal.
Calcd for C49H64O21: C, 59.51; H, 6.52. Found: C, 59.45;
H, 6.48.
L
D
A mixture of prehydrogenated 10% Pd–C catalyst
(50 mg) and 13a (250 mg, 0.25 mmol) dissolved in 1:1
MeOH–dioxane (10 mL) was shaked in a hydrogen
atmosphere (1 atm) during 12 h at 50 °C. The catalyst was
filtered off and concentrated under reduced pressure to
give an oil. A solution of the crude and NaOH (150 mg,
3.1 mmol) dissolved in 1:1:1 H2O–MeOH–THF (15 mL)
was stirred at 40 °C for 2 h, then neutralized with Dowex-
50 (Hþ form), filtered, and concentrated. The mixture
(13b) was dissolved in pyridine (10 mL) and added Ac2O
(1 mL). After 24 h at 5 °C, the solution was concentrated,
diluted with EtOAc, and washed with 20% aq HCl, satd
aq NaHCO3, and then brine. The organic phase was dried
over anhydrous Na2SO4 and evaporated under reduced
pressure. Chromatography of the residue on a silica gel
column (9:1 hexane–EtOAc) gave 13c as a white solid in
3.9. 2,3,4-Tri-O-acetyl-b-
tri-O-acetyl-b- -fucopyranosyl-(1 fi 4)]-1,3,6-tri-O-acetyl-
-galactopyranose (12c)
L
-fucopyranosyl-(1 fi 2)-[2,3,4-
L
D
A mixture of prehydrogenated 10% Pd–C catalyst
(50 mg) and 12a (250 mg, 0.25 mmol) dissolved in 1:1
MeOH–dioxane (10 mL) was shaked in a hydrogen
atmosphere (1 atm) during 12 h at 50 °C. The catalyst
was filtered off and the solution concentrated under
reduced pressure to give an oil. A solution of the crude
and NaOH (150 mg, 3.1 mmol) dissolved in 1:1:1 H2O–
MeOH–THF (15 mL) was stirred at 40 °C for 2 h, then
neutralized with Dowex-50 (Hþ form), filtered, and
concentrated. The mixture (12b) was dissolved in pyr-
idine (10 mL) and added Ac2O (1 mL). After 24 h at
5 °C, the solution was concentrated, diluted with EtOAc,
and washed with a 20% aq HCl, satd aq NaHCO3, and
then brine. The organic phase was dried over anhydrous
Na2SO4 and evaporated under reduced pressure. Chro-
matography of the residue on a silica gel column (9:1
hexane–EtOAc) gave 12c as a white solid in 45% yield;
49% yield; mp 87–88 °C; ½aŠ )35.2 (c 0.1, CHCl3); 13C
D
NMR (CDCl3, 75.5 MHz): d galactose 171.5–169.0
(CH3CO), 89.7 (C-1), 73.4 (C-4), 71.9 (C-2), 70.8 (C-3),
70.5 (C-5), 62.0 (C-6), 21.2–20.6 (CH3CO), rhamnose
(1 fi 4) 99.4 (C-1), 70.6 (C-4, C-2), 68.7 (C-3), 68.1 (C-5),
17.5 (C-6), rhamnose (1 fi 2) 99.0 (C-1), 70.6 (C-4), 70.3
(C-2), 68.7 (C-3), 67.9 (C-5), 17.5 (C-6). Anal. Calcd for
C36H50O23: C, 50.82; H, 5.92. Found: C, 50.78; H, 5.89.
mp 91–95 °C; ½aŠ )21.0 (c 0.1, CHCl3); 13C NMR
D
(CDCl3, 75.5 MHz): d galactose 171.5–169.0 (CH3CO),
89.4 (C-1), 73.4 (C-4), 71.5 (C-2), 71.0 (C-3), 70.5 (C-5),
61.9 (C-6), 21.2–20.8 (CH3CO), fucose (1 fi 4) 100.1
(C-1), 71.5 (C-3), 70.3 (C-4), 69.5 (C-2, C-5), 16.3 (C-6),
fucose (1 fi 2) 100.5 (C-1), 71.7 (C-3), 70.1 (C-2, C-4),
69.7 (C-5), 16.3 (C-6). Anal. Calcd for C36H50O23: C,
50.82; H, 5.92. Found: C, 50.75; H, 5.87.
Acknowledgements
We thank the financial support from the Conseil
ꢀ
Regional de Picardie and J. Banoub for helpful discus-
sions.
3.10. Benzyl-2,3,4-tri-O-acetyl-a-
L-rhamnopyranosyl-
-rhamnopyranosyl-
(1 fi 2)-[2,3,4-tri-O-acetyl-a-
L
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