Convergent synthesis of a trisaccharide as its 2-(trimethylsilyl)ethyl glycoside related to the flavonoid triglycoside from Gymnema sylvestre

Article abstract of DOI:10.1016/j.carres.2006.03.019

The glycone part of the flavonoid triglycoside, kaempferol 3-O-β-d-glucopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→6)-β-d-galactopyranoside, has been synthesized in good yield and stereoselectivity using N-iodosuccinimide and HClO₄-silica promoted

Full text of DOI:10.1016/j.carres.2006.03.019

Carbohydrate Research 341 (2006) 1697–1701
Note
Convergent synthesis of a trisaccharide as its 2-(trimethylsilyl)ethyl
glycoside related to the flavonoid triglycoside from
Gymnema sylvestre
Balaram Mukhopadhyay*, and Robert A. Field*
Centre for Carbohydrate Chemistry, School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK
Received 20 February 2006; received in revised form 7 March 2006; accepted 14 March 2006
Available online 5 April 2006
Abstract—The glycone part of the flavonoid triglycoside, kaempferol 3-O-b-D-glucopyranosyl-(1!4)-a-L-rhamnopyranosyl-(1!6)-
b-D-galactopyranoside, has been synthesized in good yield and stereoselectivity using N-iodosuccinimide and HClO4–silica pro-
moted glycosylations of thioglycoside donors.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Flavonoids; Antidiabetic; HClO4–silica
Flavonoid glycosides constitute an important class of
biomolecules and are isolated from fruits, vegetables
and traditional medicinal plants.1 They posses important
biological activities in the growth and development of
plants. Moreover, they are potent drug candidates hav-
ing antimicrobial, anticancer or antioxidant properties.2
The plant, Gymnema sylvestre (Retz.) Schult. (Asclepiad-
aceae), is widespread in India, China and Vietnam. It is
well known for its leaves, called ‘Gur-mar’ in India, for
the sweet taste suppressing activity3 and is used as a folk
medicine for the treatment of diabetes mellitus and in
food additives against obesity.4 Exploring the abundant
resources of G. sylvestre in China, Yu et al.5 recently re-
ported the isolation and structural characterization of a
new flavonol triglycoside, kaempferol 3-O-b-D-glucopyr-
anosyl-(1!4)-a-L-rhamnopyranosyl-(1!6)-b-D-galacto-
pyranoside (Fig. 1), which is an important biomolecule
as a potential antidiabetic drug lead. Herein, we report
a simple and high yielding stereoselective synthesis of
the trisaccharide portion of this natural product as its
2-(trimethylsilyl)ethyl glycoside (1). The 2-(trimethylsil-
yl)ethyl glycoside of the target trisaccharide was parti-
cularly attractive because it can be converted to other
glycosides via coupling to the aglycon moiety.
The synthesis was started from the known6 2-(trimeth-
ylsilyl)ethyl b-D-galactopyranoside (2). Selective protec-
tion of the primary hydroxyl group with tert-
butyldiphenylsilyl group followed by acetylation of the
other hydroxyl groups afforded the completely protected
galactoside 3 in 85% yield over two steps (Scheme 1).
Deprotection of the tert-butyldiphenylsilyl group using
1 M tetrabutylammonium fluoride7 in THF at 60 ꢁC
furnished the required acceptor 4 in 78% yield. For the
L-rhamnose moiety, the known p-tolyl 2,3,4-tri-O-acet-
yl-a-L-rhamnopyranoside (5)8 was de-O-acetylated
using sodium methoxide in methanol and converted to
its 2,3-isopropylidene derivative 6 in 87% yield using
2,2-dimethoxypropane in the presence of HClO4–silica.9
Finally, the rhamnosyl donor 7 was generated by pro-
tecting the 4-hydroxyl group of 6 as a p-methoxybenzyl
ether in 86% yield (Scheme 1).
N-Iodosuccinimide promoted glycosylation of accep-
tor 4 with donor 7 in the presence of HClO4–silica10
afforded the disaccharide 8 in 82% yield (Scheme 1).
No degraded product due to the cleavage of the acid
labile isopropylidene ketal or p-methoxybenzyl ether
*
Corresponding authors. E-mail addresses: sugarnet73@hotmail.com;
r.a.field@uea.ac.uk
Present address: Medicinal and Process Chemistry Division, Central
Drug Research Institute, Chattar Manzil Palace, PO Box 173,
Lucknow 226 001, India.
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.03.019

1698
B. Mukhopadhyay, R. A. Field / Carbohydrate Research 341 (2006) 1697–1701
OH
HO
O
O
OSE
OH
O
O
O
OH
OH
O
HO
OH
O
HO
Me
O
O
O
HO
O
HO
OH
HO
HO
OH
OH
Me
O
HO
O
1
HO
HO
HO
SE = 2(trimethylsilyl)ethyl
OH
OH
Figure 1. Structure of the flavonoid triglycoside from Gymnema sylvestre.
OH
OTBDPS
OH
HO
HO
AcO
AcO
AcO
O
a
b
O
O
OSE
STol
OSE
OSE
AcO
OH
OAc
3
OAc
4
2
STol
STol
Me
MBnO
Me
HO
O
c
d
O
Me
HO
O
O
O
O
HO
O
OH
5
7
6
OAc
O
OAc
O
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
AcO
OSE
AcO
STol
OSE
OSE
AcO
e
OAc
O
OAc
O
O
f
4 + 7
O
10
Me
O
Me
MBnO
O
O
Me
HO
O
AcO
AcO
e
O
O
O
OAc
O
O
O
11
8
9
OAc
O
OH
O
AcO
HO
HO
OSE
OSE
AcO
OAc
O
O
OH
O
g
h
Me
O
Me
O
O
O
AcO
AcO
HO
HO
O
HO
HO
OAc
OH
OH
OH
12
13
Scheme 1. Reagents and conditions: (a) (i) TBDPSCl, pyridine, rt, 6 h; (ii) Ac2O, pyridine, rt, 3 h, 85% over two steps; (b) n-Bu4NFTHF, 60 ꢁC, 1 h,
78%; (c) 2,2-dimethoxypropane, acetone, HClO4–silica, rt, 2 h, 87%; (d) p-methoxybenzyl chloride, NaH, DMF, rt, 2 h, 86%; (e) NIS, HClO4–silica,
CH2Cl2, rt, 45 min, 82%; (f) CAN, CH3CN/H2O (9:1), rt, 30 min, 87%; (g) HClO4–silica, CH3OH, 2 h, 91%; (h) NaOCH3, CH3OH, rt, 2 h, 95%.
was observed during glycosylation, which confirmed the
applicability of the HClO4–silica activation method to
glycosylations with acid labile protecting groups.
nol furnished the target trisaccharide, 2-(trimethyl-
silyl)ethyl b-D-glucopyranosyl-(1!4)-a-L-rhamnopyran-
osyl-(1!6)-b-D-galactopyranoside (13) in 95% yield.
Oxidative deprotection of the p-methoxybenzyl group
using ceric ammonium nitrate11 furnished the disaccha-
ride acceptor 9 in 87% yield. This alcohol was then glycos-
ylated with known donor, p-tolyl 2,3,4,6-tetra-O-acetyl-
1-thio-b-D-glucopyranoside (10)8 in the presence of N-
iodosuccinimide and HClO4–silica to give the blocked tri-
saccharide 11 in 87% yield. Deprotection of the isopropyl-
idene ketal using HClO4–silica in methanol12 afforded
1. Experimental
1.1. General methods
All reagents and solvents were dried prior to use accord-
ing to standard methods.14 Commercial reagents were
used without further purification unless otherwise sta-
ted. Analytical TLC was performed on Silica Gel 60-
´
the trisaccharide 12 in 91% yield. Finally Zemplen de-
O-acetylation by catalytic sodium methoxide13 in metha-

B. Mukhopadhyay, R. A. Field / Carbohydrate Research 341 (2006) 1697–1701
1699
F254 (Merck or Whatman) with detection by fluores-
cence and/or by charring following immersion in a
10% ethanolic solution of sulfuric acid. An orcinol dip,
prepared by the careful addition of concentrated sulfuric
acid (20 mL) to an ice-cold solution of 3,5-dihydroxytol-
uene (360 mg) in EtOH (150 mL) and H2O (10 mL), was
used to detect deprotected compounds by charring.
Flash chromatography was performed with Silica Gel
60 (Fluka). Optical rotations were measured at the
sodium D-line at ambient temperature, with a Perkin
Elmer 141 polarimeter. 1H NMR and 13C NMR
spectra were recorded on either a Varian Unity plus
spectrometer at 300 and 75 MHz or 400 and 100 MHz,
respectively.
Purification of the crude product by column chromato-
graphy (2:1, n-hexane/EtOAc) afforded compound 4
25
(1.5 g, 78%) as a colourless syrup. ½aꢀD +22.0 (c 1.0,
CHCl3); 1H NMR (CDCl3): d 5.36 (d, 1H, J3,4 = 3.0 Hz,
H-4), 5.21 (dd, 1H, J1,2 = 8.1 Hz, J2,3 = 10.2 Hz, H-2),
5.02 (dd, 1H, J2,3 = 10.2 Hz, J3,4 = 3.0 Hz, H-3), 4.43
(d, 1H, J1,2 = 8.1 Hz, H-1), 3.97 (m, 1H, OCH2CH2-
Si(CH3)3), 3.77 (m, 2H, H-6a, H-6b), 3.67 (m, 1H, H-5),
3.51 (m, 1H, OCH2CH2Si(CH3)3), 2.08, 2.04, 1.99 (3s,
9H, 3COCH3), 0.93 (m, 2H, OCH2CH2Si(CH3)3), 0.01
(s, 9H, OCH2CH2Si(CH3)3); 13C NMR (CDCl3): d
171.4, 170.9, 169.9 (3COCH3), 100.8 (C-1), 73.5, 71.6,
69.5, 67.3, 67.1, 60.2 (C-6), 20.7, 20.6, 20.5 (3COCH3),
17.8 (OCH2CH2Si(CH3)3), ꢁ1.6 (OCH2CH2Si(CH3)3);
HRMS calcd for C17H34NO9Si [M+NH4]+: m/z
424.2003. Found: m/z 424.2005.
1.2. 2-(Trimethylsilyl)ethyl 2,3,4-tri-O-acetyl-6-O-(tert-
butyldiphenylsilyl)-b-D-galactopyranoside (3)
1.4. p-Tolyl 2,3-O-isopropylidene-4-O-(4-methoxy-
benzyl)-1-thio-a-L-rhamnopyranoside (7)
To a solution of 2 (2 g, 7.1 mmol) in dry pyridine
(20 mL) was added tert-butyldiphenylsilyl chloride
(2.2 mL, 8.5 mmol) and the mixture was stirred at rt
for 6 h. When TLC (1:1, n-hexane/EtOAc) showed com-
plete conversion of the starting material, Ac2O (15 mL)
was added and stirring was continued for 3 h. After
complete conversion (TLC), the solvent was evaporated
under reduced pressure and co-evaporated with toluene.
The crude product thus obtained was purified by col-
umn chromatography (3:1, n-hexane/EtOAc) to afford
To a mixture of compound 5 (2 g, 7.4 mmol) in dry
acetone (30 mL), 2,2-dimethoxypropane (1.4 mL,
11.1 mmol) was added followed by HClO4–silica15
(50 mg) and the mixture stirred at rt for 2 h. When TLC
(1:1, n-hexane/EtOAc) showed complete conversion of
the starting material, the solution was neutralized with
Et3N and the solvent was evaporated and the residue
was re-dissolved in DMF. NaH (530 mg, 11.1 mmol,
50% in mineral oil) was added followed by p-methoxy-
benzyl chloride (1.3 mL, 9.6 mmol) and stirring continued
at rt for 2 h until the reaction was complete (TLC; 2:1, n-
hexane/EtOAc). The mixture was then diluted with
CH2Cl2 (50 mL), washed with H2O (3 · 50 mL). The or-
ganic phase was collected, dried (Na2SO4) and evapo-
rated. The crude residue was purified by flash
chromatography (2:1, n-hexane/EtOAc) to give com-
25
compound 3 (3.8 g, 85%) as a glass. ½aꢀD +16.0 (c 1.0,
CHCl3); 1H NMR (CDCl3): d 7.63–7.34 (m, 10H,
ArH), 5.56 (d, 1H, J3,4 = 3.0 Hz, H-4), 5.17 (dd, 1H,
J1,2 = 7.8 Hz, J2,3 = 10.5 Hz, H-2), 5.03 (dd, 1H,
J2,3 = 10.5 Hz, J3,4 = 3.0 Hz, H-3), 4.44 (d, 1H,
J1,2 = 7.8 Hz, H-1), 3.97 (m, 1H, OCH2CH2Si(CH3)3),
3.77 (m, 2H, H-6a, H-6b), 3.67 (m, 1H, H-5), 3.51 (m,
1H, OCH2CH2Si(CH3)3), 2.08, 2.04, 2.00 (3s, 9H,
3COCH3), 1.06 (s, 9H, t-BuC(Ph)2Si(CH3)3), 1.02 (m,
2H, OCH2CH2Si(CH3)3), 0.01 (s, 9H, OCH2CH2-
Si(CH3)3); 13C NMR (CDCl3) d: 170.4, 170.3, 169.6
(3COCH3), 135.7, 135.6, 133.0, 132.9, 129.9, 129.8,
129.1, 128.3, 127.8 (ArC), 100.7 (C-1), 73.3, 71.4, 69.3,
67.4, 67.1, 61.2 (C-6), 26.6, 20.7, 20.5, 18.9, 17.8, ꢁ1.6
(OCH2CH2Si(CH3)3); HRMS calcd for C34H52NO9Si
[M+NH4]+: m/z 646.3411. Found: m/z 646.3414.
25
pound 7 (2.7 g, 86%) as colourless syrup. ½aꢀD ꢁ133.1 (c
1
1.0, CHCl3); H NMR (CDCl3): d 7.38–6.86 (m, 8H,
ArH), 5.68 (s, 1H, H-1), 4.84, 4.60 (2d, AB system,
J = 11.2 Hz, CH2C6H4OCH3), 4.35 (m, 2H, H-2, H-3),
4.16 (m, 1H, H-5), 3.81 (s, 3H, CH2C6H4OCH3), 3.29
(dd, 1H, J3,4 = 7.2 Hz, J4,5 = 9.9 Hz, H-4), 2.33 (s, 3H,
SC6H4CH3), 1.53, 1.39 (2s, isopropylidene CH3), 1.23
(d, 3H, J5,6 = 6.2 Hz, H-6); 13C NMR (CDCl3): d 159.3,
137.8, 132.5, 130.5, 129.8, 129.6, 113.7 (ArC), 109.4,
84.1 (C-1), 81.1 (C-4), 78.4 (CH2–C6H4–OCH3), 76.6
(C-2), 72.6 (C-3), 66.1 (C-5), 55.2 (CH2–C6H4–OCH3),
27.9, 26.3 (isopropylidene CH3), 20.9 (SC6H4CH3), 17.8
(CCH3); HRMS calcd for C24H34NO5S [M+NH4]+:
m/z 448.2158. Found: m/z 448.2156.
1.3. 2-(Trimethylsilyl)ethyl 2,3,4-tri-O-acetyl-b-D-galacto-
pyranoside (4)
To a solution of compound 3 (3 g, 4.8 mmol) in dry THF
(20 mL) was added 1 M n-Bu4NF in THF (5 mL) and the
solution was stirred at 60 ꢁC for 1 h. When TLC (3:1, n-
hexane/EtOAc) showed complete conversion of the start-
ing material, the solvent was evaporated under reduced
pressure. The residue was dissolved in CH2Cl2 (30 mL)
and washed with H2O (2 · 30 mL); the organic layer
was collected, dried (Na2SO4) and evaporated to a syrup.
1.5. 2-(Trimethylsilyl)ethyl 2,3-di-O-isopropylidene-4-O-
(4-methoxybenzyl)-a-L-rhamnopyranosyl-(1!6)-2,3,4-
tri-O-acetyl-b-D-galactopyranoside (8)
A solution of compound 4 (1.2 g, 2.95 mmol), compound
˚
7 (1.65 g, 3.8 mmol) and activated 4 A molecular sieves

1700
B. Mukhopadhyay, R. A. Field / Carbohydrate Research 341 (2006) 1697–1701
(2.0 g) in dry CH2Cl2 (25 mL) was stirred at rt under a
nitrogen atmosphere for 3 h. Then NIS (1.1 g, 4.9 mmol)
was added followed by HClO4–silica (50 mg) and the
mixture was allowed to stir at rt for 45 min, until TLC
(3:1, n-hexane/EtOAc) showed complete disappearance
of acceptor. The mixture was diluted with CH2Cl2
(25 mL) and filtered through Celite. The filtrate was suc-
cessively washed with Na2S2O3 (3 · 50 mL), NaHCO3
(2 · 50 mL) and brine (50 mL). The organic layer was
collected, dried (Na2SO4) and evaporated. The residue
was purified by flash chromatography (3:1, n-hexane/
3.82 (m, 1H, H-5), 3.67–3.37 (m, 4H, H-50, H-6a, H-
6b, O–CH2CH2Si(CH3)3), 3.31 (m, 1H, H-40), 2.10,
2.00, 1.92 (3s, 9H, 3 · COCH3), 1.45, 1.28 (2s, 6H, iso-
0
0
propylidene CH3), 1.20 (d, 3H, J5 ;6 ¼ 6:2 Hz, CCH3),
0.89 (m, 2H, O–CH2CH2Si(CH3)3), ꢁ0.03 (s, 9H,
Si(CH3)3); 13C NMR (CDCl3): d 170.4, 170.3, 169.4
(3 · COCH3), 109.4, 100.7 (C-1), 97.5 (C-10), 78.2,
75.5, 74.2, 71.5, 71.2, 69.0, 67.4, 65.9 (OCH2CH2-
Si(CH3)3), 64.9 (C-6), 27.8, 26.0 (isopropylidene CH3),
20.6, 20.5, 20.3 (3 · COCH3), 17.7 (O–CH2CH2-
Si(CH3)3), 17.1 (C–CH3), ꢁ1.7 (Si(CH3)3); HRMS calcd
for C26H48NO13Si [M+NH4]+: m/z 610.2895. Found:
m/z 610.2897.
25
EtOAc) to give 8 (1.7 g, 82%) as a white foam. ½aꢀD
1
+16.0 (c 1.0, CHCl3); H NMR (CDCl3): d 7.25, 6.83
(2d, 4H, CH2C6H4OCH3), 5.37 (d, 1H, J3,4 = 3.3 Hz,
H-4), 5.15 (dd, 1H, J1,2 = 7.8 Hz, J2,3 = 10.8 Hz, H-2),
4.96 (dd, 1H, J2,3 = 10.8 Hz, J3,4 = 3.3 Hz, H-3), 4.91
(s, 1H, H-10), 4.74, 4.51 (2d, AB system, CH2C6H4-
1.7. 2-(Trimethylsilyl)ethyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl-(1!4)-2,3-di-O-isopropylidene-a-L-
rhamnopyranosyl-(1!6)-2,3,4-tri-O-acetyl-b-D-galacto-
pyranoside (11)
OCH3), 4.43 (d, 1H, J1,2 = 7.8 Hz, H-1), 4.15 (dd, 1H,
0
0
0
0
0
0
0
J2 ;3 ¼ 5:7 Hz, J3 ;4 ¼ 6:9 Hz, H-3 ), 4.05 (d, 1H, J2 ;3
¼
5:7 Hz, H-20), 3.98 (m, 1H, O–CH2CH2Si(CH3)3), 3.79
To a solution of disaccharide acceptor 9 (1.0 g,
1.7 mmol) and ethyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
glucopyranoside 10 (1.0 g, 2.2 mmol) in dry CH2Cl2
(m, 1H, H-5), 3.74 (s, 3H, CH2C6H4OCH3), 3.62–3.43
(m, 4H, H-50, H-6a, H-6b, O–CH2CH2Si(CH3)3), 3.11
0
˚
0
0
0
0
(dd, 1H, J3 ;4 ¼ 7:5 Hz, J4 ;5 ¼ 9:9 Hz, H-4 ), 2.08, 2.00,
1.92 (3s, 9H, 3 · COCH3), 1.44, 1.30 (2s, 6H, isopropyl-
idene CH3), 1.17 (d, 3H, J5,6 = 6.2 Hz, CCH3), 0.89 (m,
2H, O–CH2CH2Si(CH3)3), ꢁ0.03 (s, 9H, Si(CH3)3); 13C
NMR (CDCl3): d 170.2 (2), 169.3 (3 · COCH3), 159.1,
130.5, 129.5, 113.5 (ArC), 109.0, 100.6 (C-1), 97.4 (C-
10), 80.1, 78.3, 75.6, 72.2, 71.6, 71.1, 68.9, 67.3, 65.0
(OCH2CH2Si(CH3)3), 64.7 (C-6), 55.0 (CH2C6H4-
OCH3), 27.7, 26.0 (isopropylidene CH3), 20.5, 20.4,
20.3 (3 · COCH3), 17.7 (O–CH2CH2Si(CH3)3), 17.6
(C–CH3), ꢁ1.7 (Si(CH3)3); HRMS calcd for C34H56-
NO14Si [M+NH4]+: m/z 730.3470. Found: m/z 730.3472.
(20 mL) was added activated powdered 4 A molecular
sieves (2.0 g) and the mixture was stirred under nitrogen
for 2 h. NIS (640 mg, 2.9 mmol) was added, followed by
HClO4–silica (50 mg) and stirring was continued for
30 min until TLC (1:1, n-hexane/EtOAc) showed com-
plete disappearance of the acceptor. The mixture was di-
luted with CH2Cl2 (20 mL) and filtered through a Celite
pad. The filtrate was washed successively with aq
Na2S2O3 (2 · 50 mL), satd aq NaHCO3 (2 · 50 mL)
and brine (50 mL). The organic layer was separated,
dried (Na2SO4) and evaporated to a syrup. The crude
product was purified by column chromatography (1:1,
n-hexane/EtOAc) to afford pure 11 (1.4 g, 89%) as a
25
1.6. 2-(Trimethylsilyl)ethyl 2,3-di-O-isopropylidene-a-L-
rhamnopyranosyl-(1!6)-2,3,4-tri-O-acetyl-b-D-galacto-
pyranoside (9)
white foam. ½aꢀD +21.0 (c 1.0, CHCl3); 1H NMR
(CDCl3): d 5.36 (d, 1H, J3,4 = 3.6 Hz, H-4), 5.15 (t,
1H, J2 ;3 ¼ J3 ;4 ¼ 9:3 Hz, H-300), 5.12 (dd, 1H, J1,2
=
¼
¼
=
00 00
00 00
00 00
8.1 Hz, J2,3 = 10.5 Hz, H-2), 4.96 (dd, 1H, J1 ;2
7:8 Hz, J2 ;3 ¼ 9:3 Hz, H-200), 4.93 (d, 1H, J1 ;2
00 00
00 00
To a solution of compound 8 (1.5 g, 2.1 mmol) in
CH3CN and H2O (9:1, 30 mL), was added CAN
(2.3 g, 4.2 mmol) and the mixture was stirred at rt for
30 min. When TLC (2:1, n-hexane/EtOAc) showed com-
plete conversion of the starting material to a slower run-
ning component, the mixture was diluted with CH2Cl2
(50 mL) and washed with satd aq NaHCO3 (2 ·
50 mL) and brine (2 · 50 mL). The organic layer was
collected, dried (Na2SO4) and evaporated. The syrupy
residue was purified by flash chromatography (2:1,
n-hexane/EtOAc) to afford pure compound 9 (1.1 g,
7:8 Hz, H-100), 4.92 (dd, 1H, J2,3 = 10.5 Hz, J3,4
3.6 Hz, H-3), 4.91 (s, 1H, H-10), 4.85 (dd, 1H,
00
00 00
00 00
J3 ;4 ¼J4 ;5 ¼9:3 Hz, H-4 ), 4.42 (d, 1H, J1,2 = 8.1 Hz,
00
00
H-1), 4.12 (dd, 1H, J5 ;6a00 ¼5:4 Hz, J6a00;6b ¼12:3 Hz,
H-6a00), 4.05 (dd, 1H, J5 ;6b ¼2:4 Hz, J6a00;6b ¼12:3 Hz,
H-6b00), 3.98–3.87 (m, 3H, H-20, H-30, O–CH2CH2-
Si(CH3)3), 3.80 (m, 1H, H-5), 3.63–3.43 (m, 5H, H-50,
H-500, H-6a, H-6b, O–CH2CH2Si(CH3)3), 3.31 (m, 1H,
H-40), 2.04, 2.03, 2.02, 2.01, 2.00, 1.98, 1.96 (7s, 21H,
7 · COCH3), 1.43, 1.25 (2s, 6H, isopropylidene CH3),
00
00
00
25
0
0
87%) as a colourless glass. ½aꢀD +13.0 (c 1.1, CHCl3);
1.14 (d, 3H, J5 ;6 ¼6:2 Hz, CCH3), 0.86 (m, 2H, O–
CH2CH2Si(CH3)3), ꢁ0.06 (s, 9H, Si(CH3)3); 13C NMR
(CDCl3): 170.5, 170.2 (2), 169.6, 169.4 (2), 169.3
(7COCH3), 109.3, 100.6 (C-1), 98.9 (C-100), 96.9 (C-10),
78.6, 77.6, 75.5, 72.8, 71.6, 71.1, 68.9, 68.7, 67.3, 66.9,
64.2, 63.9 (C-6), 62.1 (C-600), 27.7, 26.1 (isopropylidene
1H NMR (CDCl3): d 5.38 (d, 1H, J3,4 = 3.3 Hz, H-4),
5.14 (dd, 1H, J1,2 = 7.8 Hz, J2,3 = 10.8 Hz, H-2), 4.98
(dd, 1H, J2,3 = 10.8 Hz, J3,4 = 3.3 Hz, H-3), 4.94 (s,
1H, H-10), 4.45 (d, 1H, J1,2 = 7.8 Hz, H-1), 4.04 (d,
1H, H-20), 3.98 (m, 2H, H-30, O–CH2CH2Si(CH3)3),

B. Mukhopadhyay, R. A. Field / Carbohydrate Research 341 (2006) 1697–1701
1701
CH3), 20.4 (2), 20.3 (2), 20.2, 20.1, 20.0 (7COCH3), 17.7
(O–CH2CH2Si(CH3)3), 17.1 (C–CH3), ꢁ1.7 (Si(CH3)3);
HRMS calcd for C40H66NO22Si [M+NH4]+: m/z
940.3846. Found: m/z 940.3845.
H-6b, H-6a0, H-6b00, O–CH2CH2Si(CH3)3), 1.33 (d,
0
0
3H, J5 ;6 ¼ 6:2 Hz, CCH3), 0.96 (m, 2H, O–CH2CH2-
Si(CH3)3), 0.02 (s, 9H, Si(CH3)3); 13C NMR (CD3OD):
d 105.8 (C-1), 104.4 (C-100), 102.1 (C-10), 83.7, 78.2,
78.0, 76.1, 75.0, 74.9, 72.5, 72.4, 72.1, 71.6, 70.4, 68.5,
68.0, 67.9, 62.8, 19.1 (O–CH2CH2Si(CH3)3), 18.2 (C–
CH3), ꢁ1.4 (Si(CH3)3); HRMS calcd for C23H48NO15Si
[M+NH4]+: m/z 606.2793. Found: m/z 606.2794.
1.8. 2-(Trimethylsilyl)ethyl 2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl-(1!4)-a-L-rhamnopyranosyl-(1!6)-
2,3,4-tri-O-acetyl-b-D-galactopyranoside (12)
Compound 11 (1.1 g, 1.2 mmol) was dissolved in
CH3OH (20 mL), HClO4–silica (200 mg) was added
and the mixture was stirred at rt for 2 h until TLC
(1:1, n-hexane/EtOAc) showed complete conversion of
the starting material to a slower running component.
The mixture was filtered through Celite and the solvent
was evaporated to give compound 12 (950 mg, 91%) as a
Acknowledgements
We thank Dr. Alan Haines for valuable discussions dur-
ing the course of this work. We gratefully acknowledge
the EPSRC Mass Spectrometry Service Centre, Univer-
sity of Wales, Swansea, for invaluable support.
25
white foam. ½aꢀD +27.0 (c 1.1, CHCl3); 1H NMR
(CDCl3): d 5.46 (d, 1H, J3,4 = 2.4 Hz, H-4), 5.32 (t,
Supplementary data
1H, J2 ;3 ¼ J3 ;4 ¼ 9:2 Hz, H-300), 5.19 (dd, 1H, J1,2
=
¼
00 00
00 00
00 00
8.0 Hz, J2,3 = 10.4 Hz, H-2), 5.07 (dd, 1H, J1 ;2
1H and 13C NMR spectra of compounds 1, 3, 4, 6, 7, 8,
9, 11 and 12. Supplementary data associated with this
article can be found, in the online version, at
doi:10.1016/j.carres.2006.03.019.
J2 ;3 ¼ 9:2 Hz, H-200), 4.97 (dd, 1H, J2,3 = 10.4 Hz,
00 00
J3,4 = 2.4 Hz, H-3), 4.95 (d, 1H, J1 ;2 ¼ 9:2 Hz, H-100),
00 00
4.90 (dd, 1H, J3 ;4 ¼ J4 ;5 ¼ 9:2 Hz, H-400), 4.76 (s,
00 00
00 00
1H, H-10), 4.48 (d, 1H, J1,2 = 8.0 Hz, H-1), 4.25 (dd,
1H, J5 ;6a00 ¼ 2:4 Hz, J6a00;6b ¼ 12:3 Hz, H-6a00), 4.15
00
00
(dd, 1H, J5 ;6b ¼ 5:4 Hz, J6a00;6b ¼ 12:3 Hz, H-6b00),
4.01–3.79 (m, 5H, H-20, H-30, H-6a, H-6b, O–CH2CH2-
Si(CH3)3), 3.70 (m, 1H, H-5), 3.61–3.51 (m, 3H, H-50,
H-500, O–CH2CH2Si(CH3)3), 3.43 (m, 1H, H-40), 3.17
(br d, 1H, OH), 2.76 (br s, 1H, OH), 2.16, 2.08, 2.06,
2.05, 2.02, 1.98, 1.96 (7s, 21H, 7 · COCH3), 1.23 (d,
00
00
00
References
1. Bohm, B. A. Introduction to Flavonoids; Harwood Aca-
demic Press: Amsterdam, 1998.
2. Harborne, J. B.; Baxter, H. In The Handbook of Natural
Flavonoids; John Wiley & Sons: Chichester, 1999; Vol. 1.
3. Kapoor, L. D. CRC Handbook of Ayurvedic Medicinal
Plants; CRC: Boca Raton, FL, 1990; pp 200–201.
4. Porchezhian, E.; Dobriyal, R. M. Pharmazie 2003, 58, 5–9.
5. Liu, X.; Ye, W.; Yu, B.; Zhao, S.; Wu, H.; Che, C.
Carbohydr. Res. 2004, 339, 891–895.
6. Jansson, K.; Ahlfors, S.; Frejd, T.; Kihlberg, J.; Magnus-
son, G. J. Org. Chem. 1988, 53, 5629–5647.
7. Limberg, G.; Thiem, J. Carbohydr. Res. 1995, 275, 107–
115.
8. Mukhopadhyay, B.; Kartha, K. P. R.; Russell, D. A.;
Field, R. A. J. Org. Chem. 2004, 69, 7758–7760.
9. Mukhopadhyay, B.; Russell, D. A.; Field, R. A. Carbo-
hydr. Res. 2005, 340, 1075–1080.
10. Mukhopadhyay, B.; Collet, B.; Field, R. A. Tetrahedron
Lett. 2005, 46, 5923–5925.
0
0
3H, J5 ;6 ¼ 6:2 Hz, CCH3), 0.93 (m, 2H, O–CH2CH2-
Si(CH3)3), ꢁ0.02 (s, 9H, Si(CH3)3); 13C NMR (CDCl3):
d 170.9, 170.8 (2), 170.5, 170.3, 169.5, 169.4 (7COCH3),
100.9 (C-1), 99.4 (C-100), 98.4 (C-10), 80.4, 72.8, 71.6,
71.5, 71.4, 70.9, 69.4, 68.9, 68.5, 67.5, 67.0, 65.6, 64.2
(C-6), 61.8 (C-600), 20.4 (2), 20.3 (2), 20.2, 20.1, 20.0
(7COCH3), 17.8 (O–CH2CH2Si(CH3)3), 17.1 (C–CH3),
ꢁ1.6 (Si(CH3)3); HRMS calcd for C37H62NO22Si
[M+NH4]+: m/z 900.3533. Found: m/z 900.3535.
1.9. 2-(Trimethylsilyl)ethyl b-D-glucopyranosyl-(1!4)-a-
L-rhamnopyranosyl-(1!6)-b-D-galactopyranoside (1)
11. (a) Johansson, R.; Samuelson, B. J. Chem. Soc., Perkin
Trans. 1 1984, 2371; (b) Classon, B.; Garegg, P. J.;
Samuelsson, B. Acta. Chem. Scand., Ser. B 1984, 38, 419.
12. Agarwal, A.; Vankar, Y. D. Carbohydr. Res. 2005, 340,
1661–1667.
To a methanolic solution of 12 (900 mg, 1.0 mmol),
methanolic NaOCH3 (0.5M, 0.5 mL) was added and
the solution was stirred at rt for 2 h. The solution was
neutralized with DOWEX 50W H+ resin and filtered
through cotton. The solvent was evaporated under
reduced pressure to afford the target trisaccharide 1
´
13. Zemplen, G. Ber. Dtsch. Chem. Ges. 1926, 59, 1254–1259.
14. Perrin, D. D.; Amarego, W. L.; Perrin, D. R. Purification
of Laboratory Chemicals; Pergamon: London, 1996.
15. Preparation of HClO4–silica: Immobilized perchloric acid
on silica was prepared by adding commercially available
HClO4 (0.3 mmol, as a 70% aqueous solution) to a slurry
of silica gel (5 g, 200 mesh) in Et2O (15 mL) and the
solvents were removed under reduced pressure. The
resulting free flowing powder was kept at 110 ꢁC for 2 h
and used directly in reactions.
25
(570 mg, 95%) as a white amorphous powder. ½aꢀD
1
+12.0 (c 1.0, CH3OH); H NMR (CD3OD): d 4.73 (s,
1H, H-10), 4.56 (d, 1H, J1,2 = 7.8 Hz, H-1), 4.22 (d,
1H, J1 ;2 ¼ 6:3 Hz, H-100), 3.96 (m, 1H, O–CH2CH2-
00 00
Si(CH3)3), 3.86–3.17 (m, 17H, H-2, H-20, H-200, H-3,
H-30, H-300, H-4, H-40, H-400, H-5, H-50, H-500, H-6a,