Bromonium ion-promoted glycosidic bond formation and simultaneous bromination of an activated aryl aglycon

Article abstract of DOI:10.1016/S0008-6215(01)00276-2

N-Bromosuccinimide (NBS) together with a catalytic amount of Me₃SiOTf was found to be effective for the activation of thioglycosides. Concurrently with formation of the glycosidic bond, bromination took place on the activated aromatic ring of a 4-methoxyphenyl aglycon.

Full text of DOI:10.1016/S0008-6215(01)00276-2

Carbohydrate Research 337 (2002) 31–36
www.elsevier.com/locate/carres
Bromonium ion-promoted glycosidic bond formation and
simultaneous bromination of an activated aryl aglycon
Zhi-Hui Qin, Hui Li, Meng-Shen Cai, Zhong-Jun Li*
Department of Bioorganic Chemistry, School of Pharmaceutical Sciences, Beijing Medical Uni6ersity, Beijing 100083, PR China
Received 3 May 2001; accepted 5 October 2001
Abstract
N-Bromosuccinimide (NBS) together with a catalytic amount of Me3SiOTf was found to be effective for the activation of
thioglycosides. Concurrently with formation of the glycosidic bond, bromination took place on the activated aromatic ring of a
4-methoxyphenyl aglycon. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: N-Bromosuccinimide; Thioglycoside; Bromination
1. Introduction
2. Results and discussion
2-Bromoethyl6 and 2-azidoethyl7 glycosides are use-
ful intermediates for the preparation of neoglyco conju-
gates. As shown in Table 1, in entries I–III, we utilized
NBS–Me3SiOTf as a promoter to introduce a C2 spacer
arm to glycosyl donors in good yields. For the phenyl
thioglycoside 1, the reactivity of its 3-OH group is
dramatically decreased by the neighboring tetra-
chlorophthalimido (TCP)8 group, and therefore, it
could directly couple with 2-bromo- or 2-azido-ethanol
(entries I–II) without further protection of the free
hydroxy group. Entry III shows that ethyl thiogly-
cosides can also be activated by the NBS–Me3SiOTf
method.
Thioglycosides are very frequently used as glycosyl
donors in the synthesis of oligosaccharides with a vari-
ety of promoters, such as iodonium dicollidine perchlo-
rate
(IDCP),1
N-iodosuccinimide–triflic
acid
(NIS–TfOH)2a,2b and methyl triflate.3 In addition,
Nicolaou et al.4 and Sasaki et al.5 used N-bromosuccin-
imide (NBS) alone, or NBS–TfOH, to activate phenyl
thioglycosides. As compared with NIS, NBS is more
stable and is more practical in large-scale synthesis
because of its much lower price. However, in contrast
with other activation reagents, NBS has seldom been
reported as a promoter for thioglycosides.
In our program for synthesizing glycoconjugates, we
have employed NBS–Me3SiOTf to activate phenyl and
ethyl thioglycosides to introduce spacer arms with good
yields. However, in the course of synthesis of two
disaccharides under the same conditions, using a 4-
methoxyphenyl glycoside as the glycosyl acceptor,
bromination on the aromatic ring of the
methoxyphenyl group was observed. The positions of
bromination were determined by NMR spectroscopy.
In contrast, no iodination occurred when formation of
the same disaccharides was promoted by the NIS–
TfOH method.
Entry IV, attempting to synthesize disaccharide 12
under the conditions used in entries I–III, two main
products (8 and 9) were separated in approximately 2:1
proportion. In the 13C NMR spectra of compounds 8
and 9, resonances for C-1% were observed at 97.99 and
1
98.40 ppm, respectively. In their H NMR spectra, the
coupling between H-1% and H-2% was ꢀ8.5 Hz in both
cases, clearly indicative of the b-D configuration for the
newly introduced glucosamine moiety. The most signifi-
1
cant differences in their H NMR spectra were in the
aromatic proton range of 6.8–7.0 ppm. For compound
8, there was a one-proton doublet at 6.82 ppm (Jo 9.00
Hz) and a one-proton doubled doublet at 6.96 ppm (Jo
9.00, Jm 2.90 Hz), whereas for compound 9, only a
* Corresponding author. Fax: +86-10-62367134.
E-mail address: zjli@mail.bjmu.edu.cn (Z.-J. Li).
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00276-2

32
Z.-H. Qin et al. / Carbohydrate Research 337 (2002) 31–36
one-proton singlet was observed at 7.03 ppm. These
data suggested that substitution had occurred in the
4-methoxyphenyl group. The mass spectra indicated
that compound 8 was a monobrominated product and
compound 9 was a dibrominated one. Obviously, the
brominations were caused by the bromonium ion gener-
ated from NBS and Me3SiOTf in a pattern very similar
to that described by Van Boom et al.2a
In order to simplify the 13C NMR spectra, the TCP
groups of compounds 8 and 9 were removed to yield
compounds 10 and 11, whose positions of bromination
were determined by NMR data (Scheme 1).
Table 1
Bromonium ion-promoted glycosidic bond formation and its simultaneous bromination effect

Z.-H. Qin et al. / Carbohydrate Research 337 (2002) 31–36
33
Scheme 1.
performed using Silica Gel H60. All solvents were dried
and/or distilled before use. Optical rotations were mea-
sured at rt with an AA-10R (Optical Activity Co. Ltd)
polarimeter. NMR spectra were recorded (internal stan-
dard Me4Si) with a Bruker ARX-400 or JEOL-300 type
spectrometer using CDCl3 as the solvent. Elemental
analyses were performed on a Perkin–Elmer 240C in-
strument. MALDI-TOF were taken on a LDI 1700
instrument. Melting points were determined on a X4
melting-point apparatus and are uncorrected.
For compound 10, the DEPT 135 spectrum further
confirmed it was a monobrominated product because of
the disappearance of the resonance at 111.7 ppm. Its
structure was finally determined from the NOE between
the aromatic proton (6.82 ppm, 1 H, d, Jo 9.00 Hz) and
the methoxy proton (Scheme 2), indicating that bromi-
nation occurred ortho to the methoxy group.
Similarly, the DEPT 135 spectrum of compound 11
showed it to be a dibrominated product because of
disappearance of the resonances at 110.3 and 111.8
ppm. The HMQC spectrum of this compound dis-
played one-proton singlet at l 7.09 correlated with the
13C resonance at 116.69 ppm, through which we could
assign the proton at 7.09 ppm to one of aromatic
protons of the brominated OMp ring. Among the four
possible structures (A–D) for dibrominated products,
only structure B was consistent with the NMR data for
compound 11 (Fig. 1).
In entry V, the coupling reaction between the donor
13 and the acceptor 7 was also mediated by NBS–
Me3SiOTf, and monobrominated 14 was separated as
the only main product. In entry VI, the same donor 6
and acceptor 7 were coupled in the presence of NIS–
TfOH to afford disaccharide 12 in a yield similar to
that in entry IV, but no iodination occurred. As ex-
pected, iodination was not observed in entry VII either.
In summary, NBS–Me3SiOTf can activate phenyl
and ethyl thioglycosides for the synthesis of O-gly-
cosides and disaccharides in high yields. However, con-
currently with introduction of the glycosidic bond,
bromination occurred on an activated aromatic ring in
the acceptor. Therefore, if there are no activated aro-
matic structures in either glycosyl donor and acceptor,
NBS–(cat.) Me3SiOTf is an effective and practical pro-
moter for thioglycosides. NBS, together with a catalytic
amount of Me3SiOTf is also useful as a very mild and
convenient brominating reagent in organic synthesis.
General procedure for glycosylation reactions—(a)
NBS–Me3SiOTf-mediated glycosylation reaction.—
Thioglycoside donor (1 equiv) and glycosyl acceptor
(1.5–2 equiv) were dissolved in dry CH2Cl2 under
,
argon, and pulverized activated molecular sieves (4 A)
were added. The mixture was stirred for at least 1 h at
rt and then cooled to about −50 °C. NBS (2–2.5
equiv) and Me3SiOTf (0.2 equiv) were added, stirring
was continued for 45 min at this temperature. The
solution was then diluted with CH2Cl2, filtered, and
washed successively with aq NaHCO3, NaHSO3 and
water. The organic layer was dried (MgSO4), concen-
trated, and purified by column chromatography.
(b) NIS–TfOH-mediated glycosylation. Operation
was as just described; for work up, the solution was
washed successively with aq NaHCO3, Na2S2O3, and
water. The organic layer was dried (MgSO4), concen-
trated, and purified by column chromatography.
2 - Bromoethyl 4,6 - O - benzylidene - 2 - deoxy - 2 - tetra-
chlorophthalimido-i- -glucopyranoside (2).—2-Bromo-
D
ethanol (1 mL ) reacted with the thioglycoside donor 1
(1.50 g, 2.38 mmol) following the general procedure (a).
The crude product was purified by column chromatog-
raphy, eluting with 1:4 acetone–petroleum ether to
afford the title compound as a white foam (1.10 g,
70%): mp 180–182 °C, [h]D −30.8° (c 1.7, CHCl3); Rf
3. Experimental
General methods.—All reactions were monitored by
TLC on Silica Gel GF254. Column chromatography was
Scheme 2.

34
Z.-H. Qin et al. / Carbohydrate Research 337 (2002) 31–36
Fig. 1. Four possible structures of dibrominated products.
0.40 (1:3 acetone–petroleum ether); IR (cm−1): 1710,
1770 (CꢀO); H NMR (400 MHz, CDCl3): 7.26–7.47
4.55–4.61 (m, 1 H), 4.33–4.39 (m, 1 H), 4.16–4.21 (m,
1 H), 3.99–4.06 (m, 1 H), 3.91 (br, 2 H), 3.66–3.73 (m,
1 H), 3.38–3.44 (m, 1 H), 3.26–3.31 (m, 1 H), 2.20 (s,
3 H, OAc); 13C NMR (75 MHz, CDCl3): 170.3 (CꢀO),
166.6 (CꢀO), 165.8 (CꢀO), 164.9 (CꢀO), 133.3, 129.6,
129.6, 129.1, 129.0, 128.4, 128.3 (ArꢁC), 101.2 (C-1),
72.5, 70.7, 68.9, 68.3, 66.9, 61.4 (C-2, 3, 4, 5, 6 and
OCH2CH2N3), 50.4 (OCH2CH2N3), 40.2 (ClCH2CO),
20.5 (COCH3). Anal. Calcd for C26H26ClN3O10: C,
54.22; H, 4.55; N, 7.29. Found: C, 54.30; H, 4.76; N,
7.09.
1
(m, 5 H, ArH), 5.55 (s, 1 H, PhCH), 5.27 (d, 1 H, J
8.48 Hz, H-1), 4.63 (dd, 1 H, J 10.56, 8.56 Hz, H-3),
4.36–4.40 (m, 1 H, H-2), 4.25 (dd, 1 H, J 10.50, 8.50
Hz, H-4), 4.11–4.15 (m, 1 H, H-6a), 3.73–3.82 (m, 2 H,
H-5, H-6b), 3.60–3.64 (m, 2 H, ꢁOCH2CH2Br), 3.34–
3.38 (m, 2 H, ꢁOCH2CH2Br), 2.04 (br, 1 H, OH); 13C
NMR (75 MHz, CDCl3): 140.2 (ArꢁC, TCP), 136.7,
129.4, 128.3, 128.3, 127.2, 126.1 (ArꢁC), 101.8 (PhCH),
98.8 (C-1), 81.9 (C-4), 69.6 (ꢁOCH2CH2Br), 68.5 (C-6),
68.1 (C-3), 66.3 (C-5), 56.8 (C-2), 30.4 (OCH2CH2Br).
Anal. Calcd for C23H18BrCl4NO7: C, 43.01; H, 2.82; N,
2.18. Found: C, 43.38; H, 2.92; N, 2.37.
3-Bromo-4-methoxyphenyl 3-O-acetyl-4,6-O-benzyli-
dene-2-deoxy-2-tetrachlorophthalimido-i-D-glucopyran-
osyl-(1“6)-2,3,4-tri-O-benzyl-i- -galactopyranoside (8)
D
2 - Azidoethyl 4,6 - O - benzylidene - 2 - deoxy - 2 - tetra-
and 3,6-di bromo-4-methoxyphenyl 3-O-acetyl-4,6-O-
benzylidene-2-deoxy-2-tetrachlorophthalimido-i-gluco-
chlorophthalimido-i- -glucopyranoside (3).—2-Azido-
D
ethanol (220 mL) reacted with the thioglycoside donor 1
(630 mg, 1 mmol) following the general procedure (a).
The crude product was purified by column chromatog-
raphy, eluting with 1:4 acetone–petroleum ether to
afford the title compound as a white foam (480 mg,
78%): mp 114–116 °C, [h]D −13.9° (c 1.44, CHCl3); Rf
0.34 (1:3 acetone–petroleum ether); IR (cm−1): 2102
pyranosyl - (1“6) - 2,3,4 - tri - O - benzyl - i -
D - galacto-
pyranoside (9).—The 4-methoxyphenylgalactoside ac-
ceptor 7 (1.24 g, 2.23 mmol) was glycosylated with the
thioglycoside donor 6 (1.80 g, 2.69 mmol) following the
general procedure (a). The crude product was purified
and separated by column chromatography, eluting with
1:5 EtOAc–cyclohexane to afford the title compounds
in 59% yield (compound 8, 540 mg, and 9, 1.10 g), their
ratio (8:9) being ꢀ2:1.
1
(ꢁN3), 1775, 1715 (CꢀO); H NMR (300 MHz, CDCl3):
7.36–7.47 (m, 5 H, ArH), 5.56 (s, 1 H, PhCH), 5.32 (d,
1 H, J 8.40 Hz, H-1), 4.60 (dd, 1 H, J 10.30, 8.50 Hz,
H-3), 4.36–4.41 (m, 1 H, H-2), 4.26 (dd, 1 H, J 10.80,
8.40 Hz, H-4), 3.99–4.06 (m, 1 H, H-6a), 3.80–3.86 (m,
1 H, H-6b), 3.57–3.69 (m, 3 H, OCH2CH2N3 and H-5),
3.12–3.47 (m, 2 H, OCH2CH2N3), 2.16 (br, 1 H, OH);
13C NMR (75 MHz, CDCl3): 163.8 (CꢀO, TCP), 162.8
(CꢀO, TCP), 140.2 (ArꢁC, TCP), 136.7, 129.4, 128.3,
127.2, 126.1 (ArꢁC), 101.8 (PhCH), 98.6 (C-1), 81.9
(C-4), 68.8 (OCH2CH2N3), 68.5 (C-6), 68.0 (C-3), 66.2
(C-5), 56.8 (C-2), 50.3 (OCH2CH2N3). Anal. Calcd for
C23H18Cl4N4O7: C, 45.71; H, 3.00; N, 9.27. Found: C,
45.59; H, 2.90; N, 9.07.
Compound 8 was a foam: mp 114–116 °C, [h]D
−26.3° (c 0.76, CHCl3); Rf 0.51 (3:1 cyclohexane–
1
EtOAc); H NMR (400 MHz, CDCl3): 7.22–7.44 (m,
21 H, ArH), 6.97 (dd, 1 H, Jo 8.95, Jm 2.86 Hz, OMp),
6.82 (d, 1 H, Jo 9.03 Hz, OMp), 5.71 (t, 1 H, J 9.70 Hz,
H-3%), 5.49 (s, 1 H, PhCH), 5.46 (d, 1 H, J 8.40 Hz,
H-1%), 4.97, 4.95, 4.64, 4.62 (ABq, 2 H, J 11.40 Hz,
OBn), 4.89, 4.86, 4.81, 4.78 (ABq, 2 H, J 10.90 Hz,
OBn), 4.67–4.75 (m, 3 H, OBn, H-1), 4.23–4.28 (m, 2
H, H-2%, H-6a), 4.00 (dd, 1 H, J 9.60, 7.8 Hz, H-2),
3.84–3.8 (m, 1 H, H-6a%), 3.82 (s, 3 H, OCH3), 3.68–
3.79 (m, 4 H, H-4, H-6b, H-4%, H-6b%), 3.50–3.57 (m, 3
H, H-3, H-5, H-5%), 1.91 (s, 3 H, H3CCꢀO); 13C NMR
(100 MHz, CDCl3): 170.7 (CH3CO), 163.5, 162.8 (CꢀO,
TCP), 151.9, 151.4 (C-1, C-4, OMp), 140.7 (TCP),
140.5 (TCP), 138.4, 138.3, 138.2, 136.8, 130.1, 129.8,
129.3, 128.4, 128.4, 128.3, 128.2, 128.0, 127.7, 127.5,
127.1, 126.9, 126.3 (ArꢁC), 122.9, 117.2, 112.5, 111.6
(C-2, C-3, C-5, C-6, OMp), 102.9 (C-1), 101.8 (PhCH),
97.9 (C-1%), 81.9 (C-3), 78.9 (C-2), 78.8 (C-4%), 75.4
(OCH2Ph), 74.6 (OCH2Ph), 73.5 (C-5), 73.4 (C-4), 73.1
(OCH2Ph), 70.1 (C-3%), 68.5 (C-6), 68.2 (C-6%), 66.2
2 - Azidoethyl 4 - O - acetyl - 2,6 - di - O - benzoyl - 3 -
O-chloroacetyl-i- -galactopyranoside (5).—2-Azido-
D
ethanol (300 mL) reacted with the thioglycoside donor 4
(400 mg, 0.72 mmol) following the general procedure
(a). The crude product was purified by column chro-
matography, eluting with 1:4 acetone–petroleum ether
to afford the title compound as a colorless syrup (300
mg, 73%), [h]D −10.0° (c 0.8, CHCl3); IR (cm−1): 2104
(ꢁN3), 1721 (CꢀO); 1H NMR (300 MHz, CDCl3): 7.41–
8.01 (m, 10 H, ArH), 5.54–5.59 (m, 2 H), 5.36 (dd, 1 H,
J 10.50, 2.70 Hz, H-3), 4.79 (d, 1 H, J 7.20 Hz, H-1),

Z.-H. Qin et al. / Carbohydrate Research 337 (2002) 31–36
35
(C-5%), 56.7 (OCH3), 56.2 (C-2%), 20.6 (CH3CO); FAB-
MS: 1195 [M+]. Anal. Calcd for C57H50BrCl4NO14·
H2O: C, 56.44; H, 4.29; N, 1.15. Found: C, 56.45; H,
4.22; N, 1.42.
4.54–5.00 (m, 8 H, 3×OBn, H-1, H-1%), 4.25 (dd, 1 H,
J 10.30, 5.00 Hz, H-6a%), 4.05 (dd, 1 H, J 9.60, 7.70 Hz,
H-2), 3.97 (t, 1 H, J 9.30 Hz, H-3%), 3.83 (s, 3 H,
OCH3), 3.63–3.79 (m, 5 H, H-4, H-5, H-6a, H-6b,
H-6b%), 3.59 (dd, 1 H, J 9.70, 2.80 Hz, H-3), 3.52 (t, 1
H, J 9.20 Hz, H-4%), 3.38–3.48 (m, 2 H, H-5%, H-2%),
1.69 (s, 3 H, NHCOCH3); 13C NMR (100 MHz,
CDCl3): 171.9 (ꢁNHCOꢁ), 152.0, 151.5 (C-1, C-4,
OMp), 138.3, 138.1, 138.1, 137.0, 129.2, 128.5, 128.4,
128.4, 128.4, 128.3, 128.2, 127.9, 127.9, 127.8, 127.7,
126.4 (ArꢁC), 122.6, 117.6, 112.6, 111.7 (C-2, C-3, C-5,
C-6, OMp), 103.0 (C-1), 101.9 (PhCH), 101.0 (C-1%),
81.8 (C-3), 81.5 (C-4%), 78.9 (C-2), 75.5 (OCH2Ph), 74.5
(OCH2Ph), 74.4 (C-5), 73.6 (C-4), 73.5 (OCH2Ph), 71.5
(C-3%), 69.3 (C-6), 68.5 (C-6%), 66.2 (C-5%), 59.0 (C-2%),
56.7 (OCH3); MALDI-TOF: 949.0 [M+Na]+, 964.6
[M+K]+. Anal. Calcd for C49H52BrNO12: C, 63.49; H,
5.65; Br, 8.62; N, 1.51. Found: C, 63.41; H, 5.70; Br,
8.27; N, 1.32.
Compound 9 was a foam: mp 116–118 °C, [h]D
−23.7° (c 1.18, CHCl3); Rf 0.57 (3:1 cyclohexane–
1
EtOAc); H NMR (400 MHz, CDCl3): 7.24–7.44 (m,
21 H, ArH), 7.03 (s, 1 H, OMp), 5.71 (dd, 1 H, J 9.96,
9.41 Hz, H-3%), 5.50 (s, 1 H, PhCH), 5.49 (d, 1 H, J 8.50
Hz, H-1%), 4.62–5.10 (m, 7 H, 3×OBn, H-1), 4.23–4.31
(m, 2 H, H-2%, H-6a), 4.08 (dd, 1 H, J 9.70, J 7.68 Hz,
H-2), 3.89–3.91 (m, 1 H, H-6a%), 3.82 (s, 3 H, OCH3),
3.69–3.79 (m, 4 H, H-4, H-6b, H-4%, H-6b%), 3.53–3.64
(m, 3 H, H-3, H-5, H-5%), 1.91 (s, 3 H, CH3CO); 13C
NMR (100 MHz, CDCl3): 170.8 (CH3CO), 163.5, 162.8
(CꢀO, TCP), 151.8, 148.2 (C-1, C-4, OMp), 140.7
(TCP), 140.4 (TCP), 138.4, 138.4, 138.2, 136.8, 130.1,
129.8, 129.3, 128.4, 128.3, 127.9, 127.7, 127.5, 127.1,
126.9, 126.3 (ArꢁC), 121.7, 116.5, 111.7, 110.5 (C-2,
C-3, C-5, C-6, OMp), 102.5 (C-1), 101.8 (PhCH), 98.4
(C-1%), 81.9 (C-3%), 78.8 (C-2), 78.6 (C-4%), 75.5
(OCH2Ph), 74.7 (OCH2Ph), 73.4 (C-5), 73.3 (C-4), 73.2
(OCH2Ph), 70.2 (C-3%), 68.5 (C-6), 68.2 (C-6%), 66.3
(C-5%), 56.9 (OCH3), 56.2 (C-2%), 20.6 (CH3CO);
MALDI-TOF: 1296.1 [M+Na]+, 1312.2 [M+K]+.
Anal. Calcd for C57H49Br2Cl4NO14: C, 53.75; H, 3.88;
N, 1.10. Found: C, 53.70; H, 3.84; N, 0.76.
3,6-Di-bromo-4-methoxyphenyl 2-acetamido-4,6-O-
benzylidene-2-deoxy-i-
D
-glucopyranosyl-(1“6)-2,3,4-
tri-O-benzyl-i- -galactopyranoside (11).—Compound
D
9 (210 mg, 0.16 mmol) was converted to compound 11
(a white solid, 90 mg, 55.0%) as described for com-
pound 10; [h]D −75.0° (c 0.32, CHCl3); Rf 0.33 (1:1
1
CHCl3–EtOAc); H NMR (400 MHz, CDCl3): 7.25–
7.49 (m, 21 H, ArH), 7.09 (s, 1 H, OMp), 5.67 (d, 1 H,
J 5.80 Hz, ꢁNHꢁ), 5.52 (s, 1 H, PhCH), 4.62–5.17 (m,
8 H, 3×OBn, H-1, H-1%), 4.27 (dd, 1 H, J 10.30, 4.80
Hz, H-6a%), 4.10–4.16 (m, 2 H, H-2, H-3%), 3.83 (s, 3 H,
OCH3), 3.67–3.79 (m, 5 H, H-4, H-5, H-6a, H-6b,
H-6b%), 3.35–3.44 (m, 2 H, H-5%, H-2%), 1.69 (s, 3 H,
NHCOCH3); 13C NMR (100 MHz, CDCl3): 171.8
(NHCOCH3), 151.9, 148.3 (C-1, C-4, OMp), 138.3,
138.1, 138.0, 137.0, 129.2, 128.5, 128.4, 128.4, 128.4,
128.3, 128.3, 127.9, 127.9, 127.8, 127.7, 126.4 (ArꢁC),
121.5, 116.7, 111.8, 110.3 (C-2, C-3, C-5, C-6, OMp),
102.5 (C-1), 101.9 (PhCH), 100.9 (C-1%), 81.7 (C-3), 81.6
(C-4%), 78.6 (C-2), 75.6 (OCH2Ph), 74.6 (OCH2Ph), 74.6
(C-5), 73.6 (C-4), 73.6 (OCH2Ph), 70.9 (C-3%), 69.4
(C-6), 68.5 (C-6%), 66.2 (C-5%), 59.6 (C-2%), 56.9 (OCH3),
23.2 (NHCOCH3); MALDI-TOF: 1028.6 [M+Na]+,
1044.9 [M+K]+. Anal. Calcd for C49H51Br2NO12: C,
58.51; H, 5.11; Br, 15.89; N, 1.39. Found: C, 58.47; H,
5.17; Br, 15.29; N, 1.29.
3-Bromo-4-methoxyphenyl 2-acetamido-4,6-O-ben-
zylidene-2-deoxy-i-
D
-glucopyranosyl-(1“6)-2,3,4- tri-
O-benzyl-i- -galactopyranoside (10).—Compound
D
8
(190 mg, 0.17 mmol) was dissolved in the mixture of 2
mL dry THF and 10 mL dry EtOH, and 1,2-di-
aminoethane (70 mL, 1.05 mmol) was added. The mix-
ture was heated at 60 °C for 5 h and concentrated. The
residue was filtered through a short column, and the
eluate (20:1 CHCl3–MeOH) was concentrated. The
residue was dissolved in 6 mL of pyridine, and Ac2O (4
mL) was added. The mixture was stirred at rt overnight
and then cooled in an ice bath. A few drops of water
and 5 mL of MeOH were added, and the mixture was
concentrated. The residue was dissolved in 30 mL of
CHCl3, and washed successively with water and brine.
The organic layer was dried and concentrated. The
residue was dissolved in 2 mL of CH2Cl2 and 2.5 mL of
dry MeOH. To the solution was added 0.15 mL of 1 M
NaOMe–MeOH and the mixture was stirred for 3 h.
After neutralization with H+ cation-exchange resin, the
solution was filtered and concentrated. The crude
product was purified by column chromatography, elut-
ing with 1:3 EtOAc–CHCl3 to afford the title com-
pound as a white solid mass, yield 85 mg (52%), mp
240–242 °C (dec), [h]D −63.2° (c 0.57, CHCl3); Rf 0.22
(1:1 CHCl3–EtOAc); 1H NMR (400 MHz, CDCl3):
7.25–7.49 (m, 21 H, ArH), 6.99 (dd, 1 H, Jo 9.00, Jm
2.90 Hz, OMp), 6.82 (d, 1 H, Jo 9.00 Hz, OMp), 5.65
(d, 1 H, J 5.60 Hz, ꢁNHꢁ), 5.52 (s, 1 H, PhCH),
4-Methoxyphenyl 3-acetyl-4,6-O-benzylidene-2-de-
oxy-2-tetrachlorophthalimido-i-
D
-glucopyranosyl-(1“
6)-2,3,4-tri-O-benzyl-i- -galactopyranoside (12).—The
D
4-methoxyphenylgalactoside acceptor 7 (110 mg, 0.19
mmol) was glycosylated with the thioglycoside donor 6
(170 mg, 0.25 mmol) following the general procedure
(b). The crude product was purified by column chro-
matography eluting with 5:1 cyclohexane–EtOAc to
afford title the compound as a syrup (120 mg, 54%),
[h]D −32.7° (c 0.49, CHCl3); Rf 0.53 (3:1 cyclohexane–
1
EtOAc); H NMR (400 MHz, CDCl3): 7.25–7.43 (m,

36
Z.-H. Qin et al. / Carbohydrate Research 337 (2002) 31–36
20 H, ArH), 6.77–6.96 (AA%BB, 4 H, OPMP), 5.70 (t,
1 H, J 9.70 Hz, H-3%), 5.50 (s, 1 H, PhCH), 5.45 (d, 1
H, J 8.40 Hz, H-1%), 4.61–4.97 (m, 7 H, 3×OCH2Ph
and H-1), 4.22–4.27 (m, 2 H, H-2%, H-6a), 4.00 (dd, 1
H, J 9.70, 7.40 Hz, H-2), 3.80–3.84 (m, 1 H, H-6a%),
3.74 (s, 3 H, OCH3), 3.68–3.77 (m, 4 H, H-4, H-6b,
H-4%, H-6b%), 3.50–3.55 (m, 3 H, H-3, H-5, H-5%), 1.92
(s, 3 H, OAc); 13C NMR (100 MHz, CDCl3): 170.7
(CH3CO), 163.5 (CꢀO, TCP), 162.8 (CꢀO, TCP), 155.2,
151.4 (ArꢁC, C-1, C-4, OMp), 140.6 (ArꢁC, TCP),
138.5, 138.4, 138.3, 136.8, 132.4, 129.7, 129.3, 129.0,
128.5, 128.4, 128.4, 128.3, 128.3, 128.2, 128.2, 128.1,
127.9, 127.6, 127.5, 126.3 (ArꢁC), 118.5 (2 C, OMp),
114.5 (2 C, OMp), 103.0 (C-1), 101.8 (PhCH), 97.9
(C-1%), 81.9 (C-3), 78.9 (C-2), 78.8 (C-4%), 75.3
(OCH2Ph), 74.5 (OCH2Ph), 73.6 (C-5), 73.41 (C-4),
73.2 (OCH2Ph), 70.1 (C-3%), 68.5 (C-6), 68.3 (C-6%), 68.1
(C-5%), 56.2 (OCH3), 55.6 (C-2%), 20.6 (COCH3);
MALDI-TOF: 1138.5 [M+Na]+, 1153.8 [M+K]+.
Anal. Calcd for C57H51Cl4NO14: C, 61.35; H, 4.61; N,
1.25. Found: C, 61.27; H, 4.60; N, 1.61.
tri-O-benzyl-i-
D
-galactopyranoside
(15).—The
4-
methoxyphenylgalactoside acceptor 7 (100 mg, 0.18
mmol) was glycosylated with the thioglycoside donor
13 (160 mg, 0.24 mmol) following the general procedure
(b). The crude product was purified by column chro-
matography, eluting with 4:1 cyclohexane–EtOAc to
afford the title compound as a foam (170 mg, 76%),
[h]D +6.5° (c 1.86, CHCl3); Rf 0.26 (3:1 cyclohexane–
EtOAc); 1H NHR (400 MHz, CDCl3): 7.25–7.34 (m, 15
H, ArH), 6.77–6.97 (AA%BB%, 4 H, OPMP), 5.59 (dd, 1
H, J 10.50, 9.10 Hz, H-3%), 5.41 (d, 1 H, J 8.48 Hz,
H-1%), 5.16 (t, 1 H, J 9.60 Hz, H-4%), 4.64–4.96 (m, 7 H,
3×OCH2Ph and H-1), 4.22–4.29 (m, 2 H, H-2%, H-
6a%), 3.99–4.05 (m, 2 H, H-2, H-6b%), 3.77–3.83 (m, 3
H, H-4, H-6a, H-6b), 3.76 (s, 3 H, OCH3), 3.50–3.56
(m, 3 H, H-3, H-5, H-5%), 2.04 (s, 3 H, OAc), 2.03 (s, 3
H, OAc), 1.88 (s, 3 H, OAc); 13C NMR (100 MHz,
CDCl3): 170.5 (CꢀO, OAc), 170.5 (CꢀO, OAc), 169.3
(CꢀO, OAc), 163.3 (CꢀO, TCP), 162.5 (CꢀO, TCP),
155.1, 151.2 (ArꢁC, C-1, C-4, OMp), 140.5 (ArꢁC,
TCP), 138.4, 138.3, 138.2, 132.3, 129.9, 129.3, 128.3,
128.2, 128.2, 128.1, 127.6, 127.4, 126.7 (ArꢁC), 118.2 (2
C, OMp), 114.4 (2 C, OMp), 102.5 (C-1), 97.2 (C-1%),
81.9 (C-3), 78.8 (C-2), 75.2 (OCH2Ph), 74.4 (OCH2Ph),
73.6 (C-5), 73.5 (C-4), 73.1 (OCH2Ph), 71.9 (C-5%), 70.9
(C-3%), 68.4 (C-4%), 68.2 (C-6), 61.6 (C-6%), 55.5 (OCH3),
55.4 (C-2%), 20.6 (OAc), 20.5 (OAc), 20.4 (OAc);
MALDI-TOF: 1135.3 [M+Na]+, 1151.4 [M+K]+.
Anal. Calcd for C54H51Cl4NO16·2 H2O: C, 56.50; H,
4.79; N, 1.22. Found: C, 56.36; H, 4.50; N, 1.49.
3-Bromo-4-methoxyphenyl 3,4,6-tri-O-acetyl-2-de-
oxy-2-tetrachlorophthalimido-i-
D
-glucopyranosyl-(1“
6)-2,3,4-tri-O-benzyl-i- -galactopyranoside (14).—The
D
4-methoxyphenylgalactoside acceptor 7 (550 mg, 1
mmol) was glycosylated with the thioglycoside donor
13 (870 mg, 1.30 mmol) following the general procedure
(a). The crude product was purified by column chro-
matography, eluting with 4:1 cyclohexane–EtOAc to
afford the title compound as a syrup (120 mg, 71%),
[h]D +5.5° (c 0.73, CHCl3); Rf 0.25 (3:1 cyclohexane–
1
EtOAc); H NMR (400 MHz, CDCl3): 7.24–7.34 (m,
Acknowledgements
15 H, ArH), 7.239 (d, 1 H, Jm 2.88 Hz, OMp), 7.02 (dd,
1 H, Jo 8.90, Jm 2.82 Hz, OMp), 6.85 (d, 1 H, Jo 9.06
Hz, OMp), 5.57 (dd, 1 H, J 10.50, 9.0 Hz, H-3%), 5.41
(d, 1 H, J 8.47 Hz, H-1%), 5.16 (dd, 1 H, J 10.10, 9.10
Hz, H-4%), 4.64–4.95 (m, 7 H, 3×OBn, H-1), 4.23–4.29
(m, 2 H, H-2%, H-6a%), 3.98–4.05 (m, 2 H, H-2, H-6b%),
3.85 (s, 3 H, OCH3), 3.76–3.83 (m, 3 H, H-4, H-6a,
H-6b), 3.51–3.54 (m, 3 H, H-3, H-5, H-5%), 2.03
(CH3CO), 2.02 (CH3CO), 1.88 (CH3CO); 13C NMR
(100 MHz, CDCl3): 170.6 (CH3CO), 170.5 (CH3CO),
169.4 (CH3CO), 151.8, 151.3 (C-1, C-4, OMp), 140.6
(TCP), 138.3, 138.3, 138.2, 129.9, 128.4, 128.3, 128.3,
128.3, 128.2, 128.2, 128.0, 127.7, 127.7, 127.5, 126.9
(ArꢁC), 123.0, 116.8, 112.5, 111.6 (C-2, C-3, C-5, C-6,
OMp), 102.4 (C-1), 97.2 (C-1%), 81.9 (C-3), 78.8 (C-2),
75.4 (OCH2Ph), 74.5 (OCH2Ph), 73.9 (C-5), 73.4 (C-4),
73.2 (OCH2Ph), 72.0 (C-5%), 71.0 (C-3%), 68.4 (C-4%), 68.1
(C-6), 61.7 (C-6%), 56.0 (OCH3), 55.4 (C-2%), 20.7
(CH3CO), 20.6 (CH3CO), 20.5 (CH3CO); MALDI-
TOF: 1214.1 [M+Na]+, 1229.7 [M+K]+. Anal.
Calcd for C54H50BrCl4NO16: C, 54.46; H, 4.23; N, 1.18.
Found: C, 54.01; H, 4.30; N: 0.82.
This project was supported by the National Sciences
Foundation of China and a grant from the Ministry of
Science and Technology of PR China.
References
1. Veeneman, G. H.; Van Boom, J. H. Tetrahedron Lett.
1990, 31, 275–278.
2. (a) Veeneman, G. H.; Van Leeuwen, S. H.; Van Boom, J.
H. Tetrahedron Lett. 1990, 31, 1331–1334;
(b) Konradsson, P.; Udodong, U. E.; Fraser-Reid, B.
Tetrahedron Lett. 1990, 31, 4313–4316.
3. Lonn, H. Carbohydr. Res. 1985, 139, 115–121.
4. Nicolaou, K. C.; Seitz, S. P.; Papahatjis, D. P. J. Am.
Chem. Soc. 1983, 105, 2430–2434.
5. Sasaki, M.; Tachibana, K. Tetrahedron Lett. 1991, 32,
6873–6876.
6. Dahmen, J.; Frejd, T.; Gronberg, G.; Lave, T.; Magnus-
son, G.; Noori, G. Carbohydr. Res. 1983, 116, 303–307.
7. Chernyak, A. Y.; Sharma, G. V. M.; Kononov, L. O.;
Krishna, P. R.; Levinsky, A. B.; Kochetkov, N. K. Carbo-
hydr. Res. 1992, 223, 303–309.
8. (a) Debenham, J. S.; Madsen, R.; Fraser-Reid, B. J. Am.
Chem. Soc. 1995, 117, 3302–3303;
4-Methoxyphenyl 3,4,6-tri-O-acetyl-2-deoxy-2-tetra-
(b) Castro-Palomino, J. C.; Schmidt, R. R. Tetrahedron
Lett. 1995, 36, 5343–5346.
chlorophthalimido - i -
D
- glucopyranosyl - (1“6) - 2,3,4-