FeCl3-catalyzed α-glycosidation of glycosamine pentaacetates

Article abstract of DOI:10.1016/j.carres.2008.09.003

An efficient method for the large-scale preparation of α-N-acetylglycosaminides, such as fluorogenic T_N-antigen probes and an α-GalNAc-Ser derivative, has been achieved using FeCl₃-catalyzed one-step condensation between commercially

Full text of DOI:10.1016/j.carres.2008.09.003

Carbohydrate Research 343 (2008) 3096–3099
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
FeCl -catalyzed
a-glycosidation of glycosamine pentaacetates
3
Guohua Wei , Xun Lv a,b, Yuguo Du a,b,
a
*
a
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Scienece, Chinese Academy of Sciences, Beijing 100085, China
College of Chemistry and Chemical Engineering, Graduate University of Chinese Academy of Sciences, Beijing 100049, China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 August 2008
Received in revised form 28 August 2008
Accepted 3 September 2008
Available online 9 September 2008
An efficient method for the large-scale preparation of
a
-N-acetylglycosaminides, such as fluorogenic
-catalyzed one-step
-glycosamine pentaacetates and fluorogenic acceptors
or serine acceptor) in refluxing 1,2-dichloroethane. Experimental simplicity, high -stereoselectivity,
T
N
-antigen probes and an
a-GalNAc-Ser derivative, has been achieved using FeCl
3
condensation between commercially available
D
(
a
low cost, satisfactory yield, and the environmentally benign nature are major advantages of our approach.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Glycopeptide
Mucin
Ferric chloride
a-Glycoside
T
N
-Antigen
7
1
,2-cis-2-Amino-2-deoxy glycosides are essential residues incorpo-
acetals, and anomeric deacylation. In particular, Kiso and co-
8
rated in a variety of oligosaccharides and glycoconjugates with bio-
logically important roles. However, stereoselective preparation of
workers applied anhyd ferric chloride and 2-acylamino-1-O-acet-
1
yl-2-deoxy-b-
room temperature, while Nuhn reported an
reaction of peracetylated sugar moieties with several acceptors in
the presence of FeCl in CH Cl
at 5 oC. Our model study started
from the reaction of cheap 2-acetamido-1,3,4,6-tetra-O-acetyl-2-
deoxy-b- -glucopyranose and n-nonyl alcohol in CH Cl . We first
D
-glucopyranoses to make b-glycosides in CH
2
Cl
2
at
9
1
,2-cis glycosidic bond for 2-amino-2-deoxy sugar remains a major
a-glycosidation by
2
challenge in complex oligosaccharide synthesis. Much work has
been done on this -glycosidation in order to improve the yield,
stereoselectivity, and operational simplicity. Among them, the cor-
responding 2-azido, 2,3-trans-oxazolidinone, 4,6-O-benzylide-
nyl, and 4,6-O-di-tert-butylsilylene6 glycosamine derivatives are
frequently used as key building blocks. Although great advances
have been achieved applying these modified donors, the synthetic
efficacy is always hampered because of laborious protecting group
manipulations when converting the intermediates to the desired
a
3
2
2
3
4
D
2
2
5
applied Nuhn’s method to our substrates, and obtained only the
corresponding bicyclic oxazoline derivative. When the reaction
was carried out in refluxing dichloromethane, a mixture of N-acet-
ylglucosaminides (
to 1,2-dichloroethane (DCE), and repeating the reaction under re-
flux conditions gave plausible product 1a with a 72% isolated
yield (Table 1, entry 1). Further investigation suggested that the
reaction was equally effective for either -, b-, or ,b-mixture of
N-acetyl- -glucosamine 1-acetate. On searching in the literature
it was found that ferric chloride might cause alkyl b-
glycopyranoside anomerization, forming the corresponding -iso-
mer. However, the same report has also clearly revealed that this
anomerization is not suitable for the N-acetyl- -glucosamine sub-
strate. Interestingly, when we treated pure nonyl 2-acetamido-
3,4,6-tri-O-acetyl-2-deoxy-b- -glucopyranose, prepared according
to Kiso’s procedure, with anhyd FeCl in refluxing DCE, a mixture
in favor of product ( :b = 5:1) was observed. Careful monitoring
of the process of our model reaction on TLC indicated a concomi-
tance of oxazoline intermediate, b isomer, and isomer in the early
a:b = 1:1) was observed. Changing the solvent
a
-N-acetylglycosaminides. In a collaborative project, we were re-
quired to provide hundred-gram scale products of fluorogenic T
antigen probes. Many published -glycosidation strategies were
a
N
-
a
a
a
thus tried, but no encouraging results were obtained that were
cost-effective. We would like to disclose here a practical method,
which encompasses the condensation of 2-acetamido-1,3,4,6-tet-
ra-O-acetyl-2-deoxy-D-glucopyranose (or galactopyranose) and an
aglycon acceptor in refluxing 1,2-dichloroethane in the presence
of anhyd ferric chloride.
D
D-
a
1
0
D
Ferric chloride has been applied in O-isopropylidenation, acety-
lation, anomerization, detritylation, debenzylation, deprotection of
D
8
3
a
a
*
a
Corresponding author. Fax: +86 10 62923563.
E-mail address: duyuguo@mail.rcees.ac.en (Y. Du).
0
008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.09.003

G. Wei et al. / Carbohydrate Research 343 (2008) 3096–3099
3097
Table 1
Ferric chloride-catalyzed formation of a-N-acetylglycosaminides
R1 OAc
O
R1
OAc
O
FeCl3
R2
AcO
R2
AcO
+
ROH
OAc
ClCH CH Cl
NHAc
2
2
AcHN
OR
1
2
reflux
1
2
R = H, R = AcO
1
2
R = AcO, R = H
Entry
1
Donor
Acceptor
Product
Isolated yield (%)
Stereoselectivityb
OAc
O
AcO
AcO
1
HO
72
a
AcHN
1
a
O
O
3
OAc
O
AcO
AcO
2
1
75
a
a
OH
AcHN
1
b
OAc
O
AcO
AcO
3
1
82
MeO
HO
OH
AcO
AcHN
O
OMe
1
c
OAc OAc
O
4
2
70
a
AcHN
O
2
a
OAc OAc
O
5
2
54
a
O N
OH
2
AcO
AcO
AcHN
b
2
O
O
NO
2
OAc OAc
O
HO
HO
O
O
6
2
AcHN
75
a
O
O
2
c
OAc OAc
O
O
AcO
O
71a
7
2
a/b = 4:1
OMe
AcHN
2
d
O
OMe
NHFmoc
NHFmoc
a
Overall yield.
Pure b isomers were not obtained, except for 2d.
b

3
098
G. Wei et al. / Carbohydrate Research 343 (2008) 3096–3099
stage of the reaction. The desired
a
anomer increased, and was the
For a large-scale preparation, compound 2a is taken as an
example: To a pre-heated (40 °C) 1,2-dichloroethane (500 mL) in
three-necked flask, equipped with mechanical stirrer, were
major product after 16 h in refluxing DCE. This phenomenon sug-
gested that the acid-catalyzed anomerization might have been oc-
1
1
curred in situ. To verify the reliability of this reaction, phenol and
-methoxyphenol (Table 1, entries 2–3) were also subjected to the
same reaction conditions. As we expected, products 1b and 1c
successively added anhyd CaSO
2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-
(150 g, 0.385 mol), and 2-naphanol (84 g, 0.58 mol) under an N
4
3
(50 g), anhyd FeCl (100 g),
4
D
-galactopyranose
a
2
were obtained in a yield of 75% and 82%, respectively.
atmosphere. The mixture was vigorously stirred under reflux for
16 h. When the reaction was completed (monitored by TLC), 1,2-
Encouraged by this finding, we next turned our attention to the
FeCl
O-acetyl-2-deoxy-
2-naphthol, 4-nitrophenol, and 4-methylumbelliferone) in reflux-
ing DCE. The reactions proceeded smoothly under the above reac-
tion conditions, and the products 2a, 2b, and 2c were obtained in
moderate to good yields (Table 1, entries 4–6), respectively. We
have successfully prepared compounds 2a (70% isolated yield)
and 2c (75% isolated yield) at 100-g scale with reproducible yields.
The efficient large-scale synthesis of these substrates would facili-
3
-catalyzed condensation between 2-acetamido-1,3,4,6-tetra-
3
dichloroethane and satd aq NaHCO were added with stirring until
D
-galactopyranose and fluorogenic acceptors
the reaction mixture became slightly basic. Centrifuging the reac-
tion mixture and concentrating the supernatant under diminished
pressure furnished a residue, which was then subjected to silica gel
column chromatography, to obtain 2a (128 g, 70%) as a yellowish
syrup.
(
1
.2.1. Nonyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-
glucopyranoside (1a)
+35 (c 1.1, CHCl
J 6.8 Hz, CH CH ), 1.17–1.24 (m, 12H), 1.53–1.55 (m, 2H), 1.88,
.95, 1.98, 2.03 (4s, 12H, Ac), 3.56–3.38 (m, 1H, OCH ), 3.60–
.63 (m, 1H, OCH ), 3.86–3.90 (m, 1H, H-5), 4.03 (dd, 1H, J 2.2,
a-D-
tate the substrate specificity testing of
dase, or new species screening from other living organisms. More
impressively, the -O-linked T -serine (Table 1, entry 7), which
a
-N-acetylgalactosamine-
1
[a]
D
3 3
); H NMR (400 MHz, CDCl ): d 0.82 (t, 3H,
2
3
a
N
1
3
1
1
5
a b
H
accumulates on the surface of tumor cells due to incomplete glycan
a b
H
formation in malignant cells,12 could also be prepared in 71% yield
2.3 Hz, H-6b), 4.18 (dd, 1H, J 4.6, 12.3 Hz, H-6a), 4.25–4.30 (m,
H, H-2), 4.77 (d, 1H, J 3.6 Hz, H-1), 5.06 (t, 1H, J 9.6 Hz, H-4),
.16 (t, 1H, J 9.6 Hz, H-3), 5.69 (d, 1H, J 9.6 Hz, NH); C NMR
under the above reaction conditions as a separable
a,b-mixture
(
4:1) in favor of isomer. This fast and efficient synthesis may pro-
a
13
vide an easily adaptable way toward commercial production of
mucin type glycopeptides that are currently under investigation
as vaccines against cancers.13
(
3
100 MHz, CDCl ): d 13.9, 20.4, 20.5, 20.6, 22.5, 23.0, 26.0, 29.0,
2
1
4
9.1, 29.2, 29.4, 31.7, 51.7, 61.9, 67.5, 68.1, 68.3, 71.2, 97.0 (C-1),
69.1, 169.7, 170.4, 171.1; MALDI-TOFMS: calcd for C23
H
39NO
9
:
In summary, we have developed an efficient method for the
+
73.26; found: 496.17 (M+Na) .
large-scale preparation of
rogenic T -antigen probes and an
drous FeCl was successfully applied to one-step condensation of
commercially available -galactosamine pentaacetates and fluoro-
genic acceptors (or serine acceptor), generating expected prod-
ucts in moderate to good yields in refluxing 1,2-dichloroethane.
Experimental simplicity, high -stereoselectivity, low cost, accept-
a-N-acetylglycosaminides, such as fluo-
N
a
-GalNAc–Ser derivative. Anhy-
1
.2.2. Phenyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-a-D-
3
glucopyranoside (1b)
D
), [lit.14 mp 119–120 °C;
)]; H NMR (400 MHz, CDCl ): d 1.97, 2.02,
Mp 118–120 °C; [a] +139 (c 1.8, CHCl
D 3
a
23
D
1
½aꢀ
+150 (c 0.7, CHCl
3
3
2
1
9
6
2
6
1
.04, 2.06 (4s, 12H, Ac), 4.03–4.12 (m, 2H, H-5, H-6b), 4.23 (dd,
H, J 4.6, 12.3 Hz, H-6a), 4.52-4.58 (m, 1H, H-2), 5.22 (t, 1H, J
.8 Hz, H-4), 5.48 (t, 1H, J 9.8 Hz, H-3), 5.58 (d, 1H, J 3.6 Hz, H-1),
.40 (d, 1H, J 9.3 Hz, NH), 7.05-7.10 (m, 3H, Ph), 7.30–7.33 (m,
H, Ph); C NMR (100 MHz, CDCl
1.6, 68.0, 68.3, 70.9, 95.7 (C-1), 116.4, 123.0, 129.6, 155.8, 169.2,
70.2, 170.4, 171.2; MALDI-TOFMS: calcd for C20 : 423.15;
a
able yield, and its environmentally benign nature are major advan-
tages of our approach.
1
3
3
): d 20.4, 20.5, 20.6, 22.9, 51.7,
1
1
. Experimental
H25NO
9
+
found: 446.13 (M+Na) .
.1. General methods
1
.2.3. p-Methoxyphenyl 2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy- -glucopyranoside (1c)
Mp 108–110 °C; [ ]D +139 (c 1.6, CHCl ), [lit. mp 111 °C; ½ ꢀ
The reactions were carried out in dry solvents under an N
2
a
-D
atmosphere. Optical rotations were determined at 25 °C with a
1
5
20
D
Perkin–Elmer Model 241-Mc automatic polarimeter. 1H and
NMR spectra were recorded with ARX 400 spectrometers for solu-
tions in CDCl . Chemical shifts are given in ppm downfield from
internal Me Si. Mass spectra were measured using MALDI-TOFMS
13
a
a
3
C
1
+
144 (c 1.5, CHCl
3
)]; H NMR (400 MHz, CDCl
3
): d 1.97, 2.05, 2.07,
2
4
1
3
.09 (4s, 12H, Ac), 3.78 (s, 3H, OCH
3
), 4.04–4.10 (m, 2H, H-5, H-6b),
3
.23 (dd, 1H, J 4.8, 12.3 Hz, H-6a), 4.50–4.51 (m, 1H, H-2), 5.22 (t,
H, J 10.5 Hz, H-4), 5.44 (t, 1H, J 10.5 Hz, H-3), 5.46 (d, 1H, J
.5 Hz, H-1), 5.86 (d, 1H, J 9.6 Hz, NH), 6.84–7.02 (2d, 4H, Ph);
4
with dihydroxybenzoic acid (DHB) as the matrix. Thin layer chro-
matography (TLC) was performed on silica gel HF254 with detection
1
3
3
C NMR (100 MHz, CDCl ): d 20.5, 20.6, 20.7, 23.1, 51.9, 55.6,
2 4
by charring with 30% (v/v) H SO in MeOH or in some cases by a
6
1
4
1.7, 67.9, 68.3, 71.0, 96.4 (C-1), 114.7, 117.6, 149.7, 155.4, 169.3,
UV lamp.
70.0, 170.5, 171.4; MALDI-TOFMS: calcd for
21
C H27NO10:
+
53.16; found: 476.13 (M+Na) .
1
3
.2. Typical procedure for FeCl -promoted a-O-glycosidation
For a small-scale reaction: To a solution of 2-acetamido-1,3,4,6-
tetra-O-acetyl-2-deoxy- -glucopyranose (1.2 g, 3.1 mmol) in dry
,2-dichloroethane (30 mL) were added anhyd CaSO (1.0 g), anhyd
(750 mg), and the acceptor (2 equiv). The suspension was
stirred vigorously under reflux for 16 h, at the end of which time
TLC indicated that the reaction was complete. Filtration, concentra-
tion of the filtrate, and purification of the residue on a silica gel col-
umn, using 1:1 or 2:3 EtOAc–petroleum ether as eluent, gave the
1.2.4. 2-Naphthnyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-a-D-
D
galactopyranoside (2a)
1
1
FeCl
4
[a]
D
+33 (c 0.8, CHCl
3
); H NMR (400 MHz, CDCl
3
): d 1.80, 1.96,
3
2.06, 2.20 (4s, 12H, Ac), 4.06 (dd, 1H, J 7.3, 11.3 Hz, H-6b), 4.12
(dd, 1H, J 6.6, 11.3 Hz, H-6a), 4.31–4.35 (m, 1H, H-5), 4.79–4.85
(m, 1H, H-2), 5.44–5.46 (m, 2H, J1,2 2.8, J3,4 3.5 Hz, H-1, H-3), 5.76
(d, 1H, J 3.6 Hz, H-4), 5.85 (d, 1H, J 9.3 Hz, NH), 7.21–7.24 (m, 1H,
Ph), 7.40–7.47 (m, 3H, Ph), 7.74–7.81 (m, 3H, Ph); 13C NMR
desired
a
product. The yield is shown in Table 1.
3
(100 MHz, CDCl ): d 20.4, 20.6, 20.7, 23.3, 47.9, 61.7, 67.2, 67.6,
6
8.2, 96.4 (C-1), 118.2, 124.7, 126.7, 127.1, 127.6, 129.7, 129.9,

G. Wei et al. / Carbohydrate Research 343 (2008) 3096–3099
3099
1
C
C
3
34.1, 153.5, 170.1, 170.2, 170.3, 171.0; MALDI-TOFMS: calcd for
for C33
5.62; N, 4.25.
38 2
H N O13: C, 59.10; H, 5.71; N, 4.18. Found: C, 59.36; H,
+
24
H
H
27NO
27NO
9
:
473.17; found: 496.13 (M+Na) ; Anal. Calcd for
24
9
: C, 60.88; H, 5.75; N, 2.96. Found: C, 60.54; H, 5.64; N,
.12.
Acknowledgment
1
.2.5. p-Nitrophenyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-
a
-
This work was supported by the NNSF of China (Projects
30701043, 20572128, 20621703, and 20732001).
D
-galactopyranoside (2b)
+81 (c 1.4, CHCl
), [lit.16
400 MHz, CDCl ): d 1.83, 1.97, 2.09, 2.20 (4s, 12H, Ac), 4.08 (dd,
H, J 7.3, 11.3 Hz, H-6b), 4.15 (dd, 1 H, J 6.6, 11.3 Hz, H-6a),
.33–4.36 (m, 1H, H-5), 4.83–4.86 (m, 1H, H-2), 5.54–5.56 (m,
H, J1,2 2.8, J3,4 3.5 Hz, H-1, H-3), 5.84 (d, 1H, J 3.6 Hz, H-4), 5.92
D 3
[a] +80 (c 0.4, CHCl
)]; 1H NMR
[
a]
D
3
(
3
Supplementary data
1
4
2
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2008.09.003.
1
3
(
(
6
1
4
d, 1H, J 9.3 Hz, NH), 7.17, 8.20 (2d, 4H, J 9.0 Hz, Ph); C NMR
100 MHz, CDCl ): d 20.5, 20.7, 20.72, 23.2, 48.0, 61.7, 67.3, 67.8,
8.4, 96.6 (C-1), 117.7, 125.4, 145.7, 162.4, 169.7, 170.1, 170.2,
71.1; MALDI-TOFMS: calcd for C20
91.11 (M + Na) ; Anal. Calcd for C20
3
References
H
24
N
2
O
11: 468.14; found:
1.
(a) Dwek, R. A. Chem. Rev. 1996, 96, 683–720; (b) Davis, B. G. Chem. Rev. 2002,
02, 579–602.
+
H
24
N
2
O
11: C, 51.28; H, 5.16;
1
N, 5.98. Found: C, 51.49; H, 5.02; N, 6.10.
2. (a) Demchenko, A. V. Curr. Org. Chem. 2003, 7, 35–49; (b) Demchenko, A. V.
Synlett 2003, 1225–1240.
3
.
(a) Paulsen, H.; Kolar, C.; Stenzel, W. Chem. Ber. 1978, 111, 2358–2369; (b)
Lemieux, R. U.; Ratcliffe, R. M. Can. J. Chem. 1979, 57, 1244–1251; (c)
Kärkkäinen, T. S.; Kartha, K. P.; MacMillan, D.; Field, R. A. Carbohydr. Res.
2008, 343, 1830–1834; (d) Park, J.; kawatkar, S.; Kim, J-H.; Boons, G.-J. Org. Lett.
1
.2.6. 4-Methylumbelliferyl 2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy-a-D-galactopyranoside (2c)
), [lit.16
1
[
a]
D
+179 (c 1, CHCl
400 MHz, CDCl
H, J 1.1 Hz), 4.02–4.13 (m, 2H, H-6b, H-6a), 4.21–4.25 (m, 1H,
H-5), 4.75–4.81 (m, 1H, H-2), 5.40 (dd, 1H, J 3.5, 11.5 Hz, H-3),
.45 (d, 1 H, J 3.2 Hz, H-1), 5.68 (d, 1H, J 3.5 Hz, H-4), 5.85 (d, 1H,
J 9.5 Hz, NH), 6.20 (d, 1H, J 1.0 Hz), 6.95 (dd, 1H, Ph), 7.07 (d, 1H,
Ph), 7.69–7.72 (m, 1H, Ph); 13C NMR (100 MHz, CDCl
): d 18.6,
0.5, 20.7, 20.8, 23.2, 47.8, 61.4, 66.9, 67.8, 67.9, 96.5 (C-1),
04.7, 113.0, 113.2, 115.5, 125.8, 152.0, 154.8, 158.6, 160.7,
67.7, 170.1, 170.2, 170.2; MALDI-TOFMS: calcd for C24
3
[a] +180 (c 1.5, CHCl )]; H NMR
D 3
2007, 9, 1959–1962; (e) Campo, V. L.; Carvalho, I.; Allman, S.; Davis, B. G.; Field,
(
3
3
): d 1.93, 1.98, 2.06, 2.19 (4s, 12H, Ac), 2.41 (d,
R. A. Org. Biomol. Chem. 2007, 5, 2645–2657.
4. (a) Benakli, K.; Zha, C.; Kerns, R. J. J. Am. Chem. Soc. 2001, 123, 9461–9462; (b)
Wei, P.; Kers, R. J. J. Org. Chem. 2005, 70, 4195–4198; (c) Kerns, J.; Zha, C.;
Benakli, K.; Liang, Y.-Z. Tetrahedron Lett. 2003, 44, 8069–8072; (d) Manabe, S.;
Ishii, K.; Ito, Y. J. Am. Chem. Soc. 2006, 128, 10666–10667; (e) Geng, Y.; Zhang, L.
H.; Ye, X. S. Chem. Commun. (Cambridge) 2008, 597–599; (f) Geng, Y.; Zhang, L.
H.; Ye, X. S. Tetrahedron 2008, 64, 4949–4958.
5
3
5
.
Yule, J. E.; Wong, T. C.; Ganghi, S. S.; Qiu, D. X.; Riopel, M. A.; Koganty, R. R.
Tetrahedron Lett. 1995, 36, 6839–6842.
Imamura, A.; Ando, H.; Ishida, H.; Kiso, M. Org. Lett. 2005, 7, 4415–
4418.
2
1
1
5
5
6
.
H
27NO11
:
+
7. (a) Rodebaugh, R.; Debenham, J. S.; Fraser-Reid, B. Tetrahedron Lett. 1996, 37,
477–5478; (b) Singh, P. P.; Gharia, M. M.; Dasgupta, F.; Srivastava, H. C.
05.16; found: 528.13 (M+Na) . Anal. Calcd for C24
H27NO11: C,
5
7.03; H, 5.38; N, 2.77. Found: C, 56.84; H, 5.25; N, 2.89.
Tetrahedron Lett. 1977, 18, 439–440; (c) Ding, X.; Wang, W.; Kong, F. Carbohydr.
Res. 1997, 303, 445–448; (d) Dasgupta, F.; Singh, P. P.; Srivastava, H. C.
Carbohydr. Res. 1980, 80, 346–349; (e) Sen, S. E.; Roach, S. L.; Boggs, J. K.; Ewing,
G. J.; Magrath, J. J. Org. Chem. 1997, 62, 6684–6686; (f) Prasad, K. R.; Anbarasan,
P. Tetrahedron: Asymmetry 2006, 17, 1146–1151.
1
3
.2.7. N-(Fluoren-9-yl-methoxycarbonyl)-O-(2-acetamido-
,4,6-tri-O-acetyl-2-deoxy-a-D-galactopyranosyl)-L-serine
methyl ester (2d)
+58 (c 1.6, CHCl
.05, 2.17 (4s, 12H, Ac), 3.80 (s, 3H, OCH
.13 (m, 3H, H-5, H-6b, H-6a), 4.25 (t, 1H, J 6.8 Hz), 4.46–4.60 (m,
H), 4.52–4.60 (m, 1H, H-2), 4.84 (d, 1H, J 3.4 Hz, H-1), 5.10 (dd, 1H,
8. (a) Kiso, M.; Anderson, L. Carbohydr. Res. 1979, 72, C12–C17; (b) Kiso, M.;
Anderson, L. Carbohydr. Res. 1985, 136, 309–323.
9. Chatterjee, S. K.; Nuhn, P. Chem. Commun. (Cambridge) 1998, 1729–1730.
1
[
a]
D
3
); H NMR (400 MHz, CDCl
3
): d 1.94, 1.99,
2
4
3
3
), 3.94–3.97 (m, 2H), 4.04–
10. Ikemoto, N.; Kim, O. K.; Lo, L. C.; Satyanarayana, V.; Chang, M.; Nakanishi, K.
Tetrahedron Lett. 1992, 33, 4295–4298.
11. (a) Boysen, M.; Gemma, E.; Lahmann, M.; Oscarson, S. Chem. Commun.
(
1
Cambridge) 2005, 3044–3045; (b) Hodosi, G.; Krepinsky, J. J. Synlett 1996,
59–162.
J 3.5, 11.5 Hz, H-3), 5.38 (d, 1H, J 3.5 Hz, H-4), 5.65 (d, 1H, J 9.5 Hz,
NH of serine), 5.79 (d, 1H, J 9.5 Hz, NH), 7.31–7.36 (t, 2H, Ph), 7.40–
12. Brocke, C.; Kunz, H. Bioorg. Med. Chem. 2002, 10, 3085–3112.
13. Kuduk, S. D.; Schwarz, J. B.; Chen, X.-T.; Glunz, P. W.; Sames, D.; Ragupathi, G.;
Livingston, P. O.; Danishefsky, S. J. J. Am. Chem. Soc. 1998, 120, 12474–
1
3
7
.44 (t, 2H, Ph), 7.60–7.63 (m, 2H, Ph), 7.75–7.80 (d, 2H, Ph);
C
3
NMR (100 MHz, CDCl ): d 20.7, 20.8, 20.9, 23.3, 47.2, 51.1, 52.8,
1
2486.
4. Weissmann, B. J. Org. Chem. 1966, 31, 2505–2509.
15. Tanaka, M.; Kyosaka, S.; Ito, Y. Chem. Pharm. Bull. 1973, 21, 1971–1977.
6. Voznyi, Y. V.; Afanasyeva, S. V.; Kalicheva, I. S.; Galotan, A. A. Bioorg. Khim.
991, 17, 510–516.
5
1
1
4.2, 61.4, 66.6, 66.8, 69.0, 69.9, 70.9, 96.5 (C-1), 120.0, 120.1,
25.1, 125.2, 127.1, 127.2, 127.8, 128.8, 141.3, 141.4, 143.7,
43.8, 156.1, 170.2, 170.3, 170.4, 170.6, 170.8; MALDI-TOFMS:
1
1
1
+
calcd for C33
38
H N
2
O
13: 670.24; found: 693.27 (M+Na) . Anal. Calcd