An efficient route toward 2-amino-β-D-galacto-and -glucopyranosides via stereoselective michael-type addition of 2-nitroglycals

Article abstract of DOI:10.1021/jo900609s

(Chemical Equation Presented) Under the catalysis of DMAP or PPY in CH ₂Cl₂, the Michael-type addition of nucleophiles to 2-nitrogalactal or 2-nitroglucal leads in excellent yields and stereoselectivity to the corresponding β-galacto

Full text of DOI:10.1021/jo900609s

shall preclude this anchimeric involvement of the 2-amino-
function.2b Considering these problems together, an attractive
solution is to employ 2-nitroglycals as key precursors;6 the
2-nitroglucal and galactal derivatives can be prepared readily
from glucose and galactose. Although these 2-nitroglycals were
introduced by Lemieux et al. in 1968,7 the full utility of these
derivatives in the synthesis of 2-amino-2-deoxy-glycosides has
only been explored recently by Schmidt and co-workers.6 In
general, Michael-type addition of nucleophiles to 2-nitroglucals
and 2-nitrogalactals can be high yielding and stereoselective,
leading to the 2-amino-2-deoxy-D-gluco or -galactopyranosides
(but not the manno- or talosides); and the R/ꢀ selectivity is
highly dependent on the addition partners, the base used, and
the reaction conditions. The nitro group can later be reduced
into the amino group with Raney nickel in satisfactory yields.6
Remarkably, addition of O-nucleophiles to 2-nitrogalactals
in the presence of a strong base, such as t-BuOK, mostly
provides the corresponding 2-deoxy-2-nitro-R-D-galactopyra-
nosides in satisfactory yields and high stereoselectivity.6 Thus,
Schmidt and co-workers have been able to synthesize the core
structures of the mucin-type glycoprotein which contain N-
acetylaminogalactose R-linked to the hydroxyl group of L-serine
and L-threonine.8 In the presence of weak bases or with
2-nitroglucals as Michael acceptors, the addition reaction turns
out to be ꢀ selective; however, the yield and R/ꢀ selectivity are
often unsatisfactory.9,10 Thus, the 2-amino-ꢀ-O-glycosides are
synthesized from 2-nitroglycals via conformational stereo-
control9b or via an indirect sequence, i.e., addition with thio-
phenol and subsequent use of the resulting 2-nitro thioglycosides
as glycosylation donors to couple with alcohols.11 Here we
report that highly ꢀ-selective addition of nucleophiles onto
2-nitroglycals can be achieved simply with 4-dimethylaminopy-
ridine (DMAP) or 4-(1-pyrrolidino)pyridine (PPY) as a base
and CH2Cl2 as solvent.
An Efficient Route toward 2-Amino-ꢀ-D-galacto-
and -glucopyranosides via Stereoselective
Michael-Type Addition of 2-Nitroglycals
Weihua Xue, Jiansong Sun,* and Biao Yu*
State Key Laboratory of Bioorganic and Natural Products
Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, China
byu@mail.sioc.ac.cn
ReceiVed March 25, 2009
Under the catalysis of DMAP or PPY in CH2Cl2, the
Michael-type addition of nucleophiles to 2-nitrogalactal or
2-nitroglucal leads in excellent yields and stereoselectivity
to the corresponding ꢀ-galacto- or -glucopyranosides, which
are ready precursors to the biologically significant ꢀ-D-
galactosamine and -glucosamine units.
2-Amino-2-deoxy-glycosides exist as integral structural com-
ponents in polysaccharides and glycoconjugates, such as gly-
colipids, glycoproteins, proteoglycans, and antibiotics, and are
associated with a wide range of biological processes,1 whereas
2-amino-2-deoxy-D-gluco- and -galactopyranosides are the most
common units, which occur in either R- or ꢀ-glycosidic linkage.
Synthesis of these important linkages has become a topic of
special challenge in carbohydrate chemistry since the very early
years.2,3 The synthetic obstacles include the following: (1)
Although 2-amino- and 2-acetamido-2-deoxy-D-glucose are
largely available starting materials, 2-amino-2-deoxy-D-galactose
is not. (2) The use of 2-acetamido-derivatives in the synthesis
is highly problematic, due to the oxazoline formation, O-
glycosylation of the amide moiety,4 and the usually poor
solubility. Thus, a special protecting group or a latent group
has to be employed for the 2-amino-group in the synthesis.3
(3) Construction of the 1,2-trans-ꢀ-D-glycosides can be secured
by the participation of the 2-N-protecting group (or the nitrogen
itself);5 nevertheless, synthesis of the 1,2-cis-R-D-glycosides
Schmidt et al. found that addition of methanol to 3,4,6-tri-
O-benzyl-2-nitro-D-galactal (1a) in the presence of NaOMe in
THF at room temperature gave methyl 3,4,6-tri-O-benzyl-2-
nitro-R-D-galactopyranoside (3r) as the major product in 82%
yield, while the ꢀ-anomer 3ꢀ was isolated in 10% yield (entry
1, Table 1). When Et3N was used as a base, the R/ꢀ selectivity
of the reaction was reversed, leading to the ꢀ-anomer predomi-
nantly in 80% yield, and the R-anomer was isolated in 10%
yield (entry 2).9a We found that DMAP (1.0 equiv), a weaker
base (pKa 9.70) than Et3N (pKa 10.65), was better to promote
the ꢀ selective addition of methanol to galactal 1a. In fact, no
R-anomer was detected (entry 3); and the yield of the ꢀ-galac-
toside 3ꢀ could be raised to 97% when the reaction was
(6) (a) Reddy, B. G.; Schmidt, R. R. Nat. Protoc. 2008, 3, 114. (b) Schmidt,
R. R.; Vankar, Y. D. Acc. Chem. Res. 2008, 41, 1059.
(7) Lemieux, R. U.; Nagabhushan, T. L.; O’Neill, I. K. Can. J. Chem. 1968,
46, 413.
(8) (a) Winterfeld, G. A.; Schmidt, R. R. Angew. Chem., Int. Ed. 2001, 40,
2654. (b) Winterfeld, G. A.; Khodair, A. I.; Schmidt, R. R. Eur. J. Org. Chem.
2003, 1009.
(1) (a) Schauer, R. AdV. Carbohydr. Chem. Biochem. 1982, 40, 131. (b)
Hakomori, S. Annu. ReV. Immunol. 1984, 2, 103. (c) Dwek, R. A. Chem. ReV.
1996, 96, 683. (d) Zachara, N. E.; Hart, G. W. Chem. ReV. 2002, 102, 431.
(2) (a) Ro¨hle, G.; Wulff, G. Angew. Chem., Int. Ed. Engl. 1974, 13, 157. (b)
Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155.
(3) (a) Banoub, J.; Boullanger, P.; Lafont, D. Chem. ReV. 1992, 92, 1167.
(b) Debenham, J.; Rodebaugh, R.; Fraser-Reid, B. Liebigs Ann. 1997, 791. (c)
Bongat, A. F. G.; Demchenko, A. V. Carbohydr. Res. 2007, 342, 374.
(4) Liao, L.; Auzanneau, F.-I. J. Org. Chem. 2005, 70, 6265.
(5) (a) Yang, Y.; Yu, B. Tetrahedron Lett. 2007, 48, 4557. (b) Chen, J.; Yu,
B. Tetrahedron Lett. 2008, 49, 1682.
(9) (a) Das, J.; Schmidt, R. R. Eur. J. Org. Chem. 1998, 1609. (b) Geiger,
J.; Reddy, B. G.; Winterfeld, G. A.; Weber, R.; Przybylski, M.; Schmidt, R. R.
J. Org. Chem. 2007, 72, 4367.
(10) Holzapfel, C. W.; Marais, C. F.; van Dyk, M. S. Synth. Commun. 1988,
18, 97.
(11) Barroca, N.; Schmidt, R. R. Org. Lett. 2004, 6, 1551.
10.1021/jo900609s CCC: $40.75  2009 American Chemical Society
Published on Web 05/19/2009
J. Org. Chem. 2009, 74, 5079–5082 5079

TABLE 1. Michael-Type Addition of Methanol to
3,4,6-Tri-O-benzyl-2-nitro-D-galactal (1a)
TABLE 2. DMAP-Catalyzed Michael-Type Addition of
Nucleophiles to 3,4,6-Tri-O-benzyl-2-nitro-D-galactal (1a)
entry
base (equiv)
solvent
yield,a
%
R/ꢀ
19a
29a
3
4
5
6
7
8
9
NaOMe (0.2)
NEt3 (>10)
THF
THF
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
92
90
91
97
93
90
20
39
78
41
8:1
1:8
0:1b
0:1
0:1
0:1
0:1
1:5b
0:1
0:1
DMAP (1.0)
DMAP (1.0)
DMAP (0.5)
DMAP (0.15)
DMAP (0.03)
DMAP (0.15)
DMAP (0.15)
DMAP (0.15)
toluene
CH3CN
10
a Isolated yield. b Determined by HPLC.
performed in CH2Cl2 (entry 4). The addition proceeded slower
when a catalytic amount of DMAP (down to 0.15 equiv) was
used, while the ꢀ-adduct 3ꢀ was still isolated as the sole product
in 90% yield within 24 h (entries 5 and 6). However, further
reducing the amount of DMAP to 0.03 equiv made the reaction
hardly proceed (entry 7). THF, toluene, and acetonitrile were
then tested as the reaction solvent when 0.15 equiv of DMAP
was used as the base (entries 8-10). The reaction became much
more sluggish than in CH2Cl2 and provided the ꢀ-galactoside
3ꢀ in 39%, 78%, and 41% yield, respectively. Moreover, the
stereoselectivity of the reaction in THF was compromised (R/ꢀ
) 1:5).
With DMAP (0.15 equiv) as base and CH2Cl2 as solvent, we
then examined the generality of this ꢀ-selective addition of
2-nitrogalactal (1a) with nucleophiles (Table 2). A panel of
alcohols (2b-j) were selected as nucleophiles, including the
functionalized primary alcohols 2b and 2c, the primary sugar
alcohols 2d and 2e, the serine and threonine derivatives 2f and
2i, the secondary 2-propanol 2g and steroidal 2h, and the highly
hindered glucose 4-ol 2j. All the addition reactions, except with
2j, provided the corresponding ꢀ-galactosides (4ꢀ-10ꢀ) in high
yields (82-96%) and satisfactory stereoselectivity (R/ꢀ > 6.5:
1; entries 1-8). Among them, the addition with achiral alcohols
2c and 2g and the L-serine and -threonine derivatives 2f and 2i
afforded the ꢀ-galactosides exclusively. Addition with methyl
2,3,6-tri-O-benzyl-R-D-glucopyranoside 2j was an exception,
leading to the R-galactoside 12r as the sole product in 69%
yield (entry 9). The substantially lower yield might be attributed
to the highly steric demanding property of the 4-OH of 2j, and
the “double stereodifferentiation” of the coupling partners (1a
and 2j) preclude formation of the ꢀ-product.12 Diethyl malonate
(2k) and thiophenol (2l) as C- and S-nucleophiles,11,13 respec-
tively, were also examined to react with 2-nitrogalactal (1a)
under the present conditions (entries 10 and 11), and the
corresponding ꢀ-C- and S-galactosides 13ꢀ and 14ꢀ were
isolated as the sole products in excellent yields (88% and 93%,
respectively).
R/ꢀ selectivity. Under the catalysis of DMAP (0.2 equiv) in
CH2Cl2, the addition of methanol to 3,4,6-tri-O-benzyl-2-nitro-
D-glucal (1b)11 proceeded smoothly, providing the expected
methyl ꢀ-glucoside 15ꢀ predominantly in 85% yield, with the
R-anomer being isolated in 9% yield (entry 1, Table 3).
However, under similar conditions, the addition of 2-(trimeth-
ylsilyl)ethanol (2c) with glucal 1b became sluggish; the corre-
sponding ꢀ-glucoside 16ꢀ was isolated as the sole product but
in only 50% yield (entry 2). With the primary sugar alcohols
2d and 2e, respectively, as nucleophiles, the addition reaction
hardly proceeded, providing the ꢀ-glucoside 17ꢀ and 18ꢀ in
only ∼20% yield (entries 4 and 6). Interestingly, replacement
of DMAP with 4-(1-pyrrolidino)pyridine (PPY)14 as the base
improved substantially the above addition reactions; the expected
ꢀ-adducts 16ꢀ, 17ꢀ, and 18ꢀ were furnished in 95%, 71%, and
77% yield, respectively, without detection of the R-anomers
(entries 3, 5, and 7). Under the catalysis of PPY, the addition
of 2-propanol 2g and thiophenol 2l, respectively, with 2-nitro-
Compared to the Michael-type addition with 2-nitrogalactals,
addition with 2-nitroglucals suffers with moderate yield and poor
(12) Spijker, N. M.; van Boeckel, C. A. A. Angew. Chem., Int. Ed. Engl.
1991, 30, 180.
(13) Pachamuthu, K.; Gupta, A.; Das, J.; Schmidt, R. R.; Vankar, Y. D. Eur.
J. Org. Chem. 2002, 1479.
(14) Scriven, E. F. V. Chem. Soc. ReV. 1983, 12, 129.
5080 J. Org. Chem. Vol. 74, No. 14, 2009

Thus, the R-glycosyl pyridinium species A was formed.17 SN2-
type substitution of a nucleophile from the ꢀ side of the
R-pyridinium A and protonation of the axial C2 anion led to
the corresponding ꢀ-galactoside or -glucoside product. Compar-
ing the reaction of galactose and glucose series, the ꢀ orientation
of the 4-O-substitution in the galactose derivatives is more
advantageous than the R orientation in the glucose counterparts
for the formation of the R-pyridinium species A. Thus, the
addition of 2-nitrogalactals is easier than that of the 2-nitro-
glucals. And PPY, which is more nucleophilic than DMAP,14
is better to undergo addition with the 2-nitroglycal to form the
R-pyridinium species A, thus it is a better catalyst for the
reaction.
TABLE 3. DMAP or PPY-Catalyzed Michael-Type Addition of
Nucleophiles to 3,4,6-Tri-O-benzyl-2-nitro-D-glucal (1b)
In summary, under the catalysis of DMAP or PPY in CH2Cl2,
the Michael-type addition of nucleophiles to 2-nitro-galactal or
-glucals leads to the corresponding ꢀ-galacto- or -glucopyra-
nosides in high yields and stereoselectivity. This protocol
provides an efficient and expeditious approach to the synthesis
of 2-amino-2-deoxy-ꢀ-D-galacto- and -glucopyranosides, which
are integral units in many important oligosaccharides, polysac-
charides, and glycoconjugates. Improvement in the addition of
2-nitroglucals with sterically demanding nucleophiles and the
mechanistic study of this addition reaction are currently
underway, and the results will be reported in due course.
Experimental Section
Typical Procedure for the Michael Addition with 3,4,6-Tri-
O-benzyl-2-nitro-D-galactal (1a). N-Boc-L-serine methyl ester 2f
(33 mg, 0.15 mmol) was added to a mixture of 2-nitro-D-galactal
1a (46 mg, 0.1 mmol) and DMAP (2 mg) in CH2Cl2 (1 mL) in the
presence of 4 Å MS. After the mixture was stirred at room
temperature for 24 h, 4 Å MS was removed by filtration. The filtrate
was concentrated at reduced pressure. The residue was purified by
silica gel column chromatography to provide O-(3,4,6-tri-O-benzyl-
2-deoxy-2-nitro-ꢀ-D-galactopyranosyl)-N-Boc-L-serine methyl ester
(8) as a colorless syrup (60 mg, 91%).
SCHEME 1. A Plausible Mechanism for the
DMAP-Catalyzed ꢀ-Selective Michael-Type Addition
Typical Procedure for the Michael Addition with 3,4,6-Tri-
O-benzyl-2-nitro-D-glucal (1b). Methyl 2,3,4-tri-O-benzyl-R-D-
glucopyranoside 2e (93 mg, 0.2 mmol) was added to a mixture of
2-nitro-D-glucal 1b (46 mg, 0.1 mmol) and PPY (3 mg) in CH2Cl2
(1 mL) in the presence of 4 Å MS. After the solution was stirred
at room temperature for 24 h, 4 Å MS was removed by filtration.
The filtrate was concentrated in vacuo. The residue was purified
by silica gel column chromatography to provide methyl 2,3,4-tri-
O-benzyl-6-O-(3,4,6-tri-O-benzyl-2-deoxy-2-nitro-ꢀ-D-glucopyra-
nosyl)-R-D-glucopyranoside (18ꢀ) as a colorless syrup (71 mg,
77%).
[2-(2-Chloroethoxyl)ethoxy]ethyl 3,4,6-tri-O-benzyl-2- deoxy-
2-nitro-ꢀ-D-galactopyranoside (4ꢀ): [R]20D +12.7 (c 0.8, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.38-7.23 (m, 15H), 4.88-4.84
(m, 3H), 4.63-4.45 (m, 5H), 4.08-3.88 (m, 3H), 3.76-3.56
(m,14H); 13C NMR (75 MHz, CDCl3) δ 137.8, 137.5, 136.6, 128.6,
128.5, 128.3, 128.2, 128.0, 127.9, 127.8 (2C), 100.2, 87.5, 79.4,
74.8, 73.7, 73.6, 72.3, 71.4, 71.3, 70.7, 70.5, 70.2, 69.0, 68.0, 42.8,
29.7; HRMS (ESI) calcd for C33H40ClNO9Na [M + Na]+ 652.2347,
found 652.2296.
glucal 1b also led to the ꢀ-glucosides in excellent yields (92%
and 88%) with complete stereoselectivity (entries 8 and 10).
However, addition of more sterically demanding acceptors with
2-nitroglucal 1b hardly took place; for example, no reaction
happened with glucose 4-ol 2j as a nucleophile under the present
conditions (entry 9).
A plausible mechanism, as shown in Scheme 1, was put
forward to explain the present ꢀ-selective addition reaction of
2-nitroglycals. DMAP acted as a nucleophile, in analogy to its
role in the Morita-Baylis-Hillman reaction,15 to attack the
anomeric C1 of the Michael acceptor 2-nitroglycal. Approaching
O-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-ꢀ-D-galactopyranosyl)-
N-Boc-L-serine methyl ester (8ꢀ): [R]20D +116.7 (c 0.5, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.38-7.22 (m, 15H), 5.25 (d, J )
7.8 Hz, 1H,), 4.87 (d, J ) 11.1 Hz, 1H), 4.83 (d, J ) 9.3 Hz, 1H),
4.73 (d, J ) 7.8 Hz, 1H), 4.62 (AB, 2H), 4.50-4.44 (m, 3H),
4.40-4.37 (m, 1H), 4.22 (dd, J ) 2.7, 10.2 Hz, 1H), 4.05-3.99
4
DMAP from the R side of the glycal, which adopts the H5
conformation, was favored, due to stereoelectronic effects.16
(15) (a) Shi, M.; Li, C.; Jiang, J. Chem. Commun. 2001, 833. (b) Porzelle,
A.; Williams, C. M.; Schwartz, B. D.; Gentle, I. R. Synlett 2005, 2923.
(16) Deslongchamps, P. Stereoelectronic Effects in Organic Chemistry;
Pergamon Press: Oxford, UK, 1983; pp 29-40.
(17) (a) Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; James, K. J. Am.
Chem. Soc. 1975, 97, 4056. (b) Zhu, J.; Bennet, A. J. J. Am. Chem. Soc. 1998,
120, 3887.
J. Org. Chem. Vol. 74, No. 14, 2009 5081

(m, 2H), 3.79 (dd, J ) 3.6, 10.5 Hz, 1H), 3.71 (s, 3H), 3.63-3.57
(m, 3H), 1.44 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 170.2, 137.8,
137.5, 136.5, 128.6 (2C), 128.4, 128.3, 128.2, 128.0 (2C), 127.9,
100.4, 86.9, 80.1, 79.3, 77.24, 74.9, 74.0, 73.6, 72.4, 71.4, 69.5,
67.7, 53.7, 52.6, 28.3; HRMS (ESI) calcd for C36H44N2O11Na [M
+ Na]+ 703.2819, found 703.2860.
(m, 5H), 4.19- 4.10 (m, 5H), 4.05 (d, J ) 2.1 Hz, 1H), 3.73 (t, J
) 6.7 Hz, 1H), 3.57-3.55 (m, 3H), 1.24 (t, J ) 7.2 Hz, 3H), 1.13
(t, J ) 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 166.1, 165.3,
138.0, 137.7, 136.7, 128.5 (2C), 128.3, 128.2, 128.0, 127.9, 127.7,
85.6, 80.2, 77.5, 74.9, 74.8, 73.5, 72.5, 72.1, 67.8, 62.0, 61.9, 53.8,
13.9, 13.8; HRMS (ESI) calcd for C34H39NO10Na [M + Na]+
644.2489, found 644.2472.
Diosgenyl 3,4,6-tri-O-benzyl-2-deoxy-2-nitro-r-D-galactopy-
ranoside (10r): [R]25D +34.2 (c 0.3, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 7.35-7.21 (m, 15H), 5.42 (d, J ) 4.3 Hz, 1H), 5.27 (d,
J ) 4.1 Hz, 1H), 4.98 (dd, J ) 4.3, 10.6 Hz, 1H), 4.85 (d, J )
11.2 Hz, 1H), 4.78 (AB, J ) 10.8 Hz, 2H), 4.50-4.38 (m, 5H),
4.12 (t, J ) 6.5 Hz, 1H), 4.01 (d, J ) 2.6 Hz, 1H), 3.57-3.55 (m,
2H), 3.48-3.37 (m, 3H), 2.30 (d, J ) 7.8 Hz, 2H), 2.00-1.95 (m,
2H), 1.88-0.78 (m, 35H); 13C NMR (125 MHz, CDCl3) δ 140.4,
138.1, 137.8, 137.5, 128.5 (2C), 128.3, 128.2, 128.1, 128.0, 127.8,
121.9, 109.3, 95.1, 84.7, 80.8, 78.7, 75.1, 73.6, 73.4, 73.1, 69.7,
68.5, 66.9, 62.1, 56.5, 50.0, 41.6, 40.3, 39.8, 39.7, 36.8, 32.1, 31.9,
31.4, 30.3, 29.7, 28.8, 27.3, 20.8, 19.4, 17.1, 16.3, 14.5; HRMS
(ESI) calcd for C54H70NO9 [M + H]+ 876.5030, found 876.5037.
Diosgenyl 3,4,6-tri-O-benzyl-2-deoxy-2-nitro-ꢀ-D-galactopy-
ranoside (10ꢀ): [R]25D -40.0 (c 1.0, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 7.36-7.23 (m, 15H), 5.30-5.28 (m, 1H), 4.86-4.82 (m,
3H), 4.61 (d, J ) 12.7 Hz, 1H), 4.56 (d, J ) 11.4 Hz, 1H), 4.47
(d, J ) 11.3 Hz, 3H), 4.42 (dd, J ) 7.4, 15.3 Hz, 1H), 4.05 (dd, J
) 2.2, 9.6 Hz, 1H), 3.98 (d, J ) 2.5 Hz, 1H), 3.65-3.58 (m, 3H),
3.50-3.45 (m, 2H), 3.39 (t, J ) 10.9 Hz, 1H), 2.04-0.77 (m, 37H);
13C NMR (125 MHz, CDCl3) δ 140.1, 137.9, 137.7, 136.6, 128.5
(2C), 128.3 (2C), 128.2, 127.9 (2C), 127.8, 121.8, 109.3, 98.7, 87.8,
80.8, 79.6, 79.3, 74.7, 73.8, 73.6, 72.2, 71.4, 68.1, 66.8, 62.1, 56.5,
50.1, 41.6, 40.2, 39.8, 38.0, 37.1, 36.8, 32.1, 31.8, 31.4, 30.3, 29.3,
28.8, 20.8, 19.3, 17.1, 16.2, 14.5; HRMS (ESI) calcd for
C54H69NO9Na [M + Na]+ 898.4861, found 898.4873.
O-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-ꢀ-D-galactopyranosyl)-
N-Boc-L-threonine allyl ester (11ꢀ): [R]25D +19.9 (c 0.5, CDCl3);
1H NMR (300 MHz, CDCl3) δ 7.38-7.22 (m, 15H), 5.85-5.75
(m, 1H), 5.25-5.07 (m, 3H), 4.87 (d, J ) 11.4 Hz, 1H), 4.78-4.69
(m, 2H), 4.63 (d, J ) 11.7 Hz, 1H), 4.54 (d, J ) 7.5 Hz, 3H),
4.46-4.44 (m, 3H), 4.37-4.35 (m, 1H), 4.28 (d, J ) 9.6 Hz, 1H),
4.00 (d, J ) 6.6 Hz, 1H), 3.61-3.50 (m, 3H), 1.46 (s, 9H), 1.13
(d, J ) 6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.9, 156.1,
137.8, 137.5, 136.5, 131.7, 128.5 (2C), 128.3, 128.2, 128.1, 128.0,
127.9, 127.8 (2C), 118.3, 98.3, 87.3, 80.0, 79.2, 75.1, 74.9, 73.6,
72.2, 71.4, 67.4, 65.9, 58.1, 28.3, 16.4; HRMS (ESI) calcd for
C39H48N2O11 [M + Na]+ 743.3167, found 743.3155.
Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-nitro-ꢀ-D-glucopyrano-
1
side (15ꢀ): [R]25 +13.3 (c 1.0, CHCl3); H NMR (300 MHz,
D
CDCl3) δ 7.34-7.16 (m, 15 H), 4.80-4.49 (m, 8H), 4.28 (t, J )
9.3 Hz, 1H), 3.76-3.70 (m, 3H), 3.58 (dt, J ) 3.0, 9.9 Hz, 1H),
3.50 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 137.7, 137.4, 136.9,
128.5, 128.4 (2C), 128.1, 128.0 (2C), 127.8 (3C), 127.6, 100.7,
89.6, 81.3, 77.5, 75.4, 75.2, 75.1, 73.5, 67.9, 57.3; HRMS (ESI)
calcd for C28H31NO7Na [M + Na]+ 516.2013, found 516.1999.
(2-Trimethylsilyl)ethyl 3,4,6-tri-O-benzyl-2-deoxy-2-nitro-ꢀ-
1
D-glucopyranoside (16ꢀ): [R]25 +2.6 (c 1.0, CHCl3); H NMR
D
(300 MHz, CDCl3) δ 7.33-7.17 (m, 15H), 4.81-4.49 (m, 8H),
4.28 (t, J ) 9.6 Hz, 1H), 4.04-3.96 (m, 1H), 3.77-3.69 (m, 3H),
3.59-3.50 (m, 2H), 0.97-0.86 (m, 2H), 0.01 (s, 9H); 13C NMR
(75 MHz, CDCl3) δ 137.7, 137.4, 136.9, 128.5, 128.4 (2C), 128.1
(2C), 128.0, 127.9, 127.8 (2C), 127.7 (2C), 99.4, 89.8, 81.4, 77.6,
75.4, 75.2, 75.1, 73.5, 68.0, 67.8, 17.7, -1.5; HRMS (ESI) calcd
for C32H41NO7SiNa [M + Na]+ 602.2551, found 602.2544.
Methyl 2,3,4-tri-O-benzyl-6-O-(3,4,6-tri-O-benzyl-2-deoxy-2-
nitro-ꢀ-D-glucopyranosyl)-r-D-glucopyranoside (18ꢀ): [R]25
D
1
+10.9 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3) δ 7.34-7.16
(m, 30H), 4.99 (d, J ) 10.8 Hz, 1H), 4.89-4.72 (m, 6 H),
4.66-4.48 (m, 7H), 4.42 (d, J ) 11.1 Hz, 1H), 4.28 (dd, J ) 9.3,
9.9 Hz, 1H), 4.11 (d, J ) 10.5 Hz, 1H), 4.00 (t, J ) 9.0, 1H),
3.76-3.64 (m, 5H), 3.57-3.50 (m, 2H), 3.45 (t, J ) 9.6 Hz, 1H),
3.35 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 138.6, 138.2, 138.1,
137.8, 137.4, 136.8, 128.5, 128.4 (4C), 128.1 (2C), 128.0 (3C),
127.9, 127.8, 127.7 (2C), 127.6 (3C), 100.0, 98.1, 89.4, 82.0, 81.4,
79.6, 77.4 (2C), 75.8, 75.5, 75.4, 75.1, 74.8, 73.4 (2C), 69.4, 68.7,
68.1, 55.2; HRMS (ESI) calcd for C55H59NO12Na [M + Na]+
948.4019, found 948.4024.
Acknowledgment. This work is supported by the National
Natural Science Foundation of China (20621062 and 90713003),
the Chinese Academy of Sciences (KJCX2-YW-H08), and the
Committee of Science and Technology of Shanghai (07DZ22001).
Supporting Information Available: 1H and 13C NMR
spectra for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
Diethyl (3,4,6-tri-O-benzyl-2-deoxy-2-nitro-ꢀ-D-galactopyra-
nosyl)malonate (13ꢀ): [R]25D +26.2 (c 1.0, CHCl3); 1H NMR (500
MHz, CDCl3) δ 7.35-7.23 (m, 15H), 5.24 (t, J ) 10.1 Hz, 1H),
4.84 (d, J ) 11.2 Hz, 1H), 4.65 (d, J ) 11.3 Hz, 1H), 4.52-4.38
JO900609S
5082 J. Org. Chem. Vol. 74, No. 14, 2009