Synthesis of amino-bridged oligosaccharide mimetics

Article abstract of DOI:10.1002/ejoc.200901106

Synthesis of amino-bridged oligosaccharides using reductive animation opens rapid access to novel glycomimetic target structures as potential ligands for the receptor protein NKR P1 of natural killer cells. Emphasis was laid on fast and facile synthetic routes. The carbonyl building blocks were easily obtained by oxidation with Dess-Martin periodinane or iodoxybenzoic acid (IBX). For the required amino-function-alized units, reduction of azide precursors was advantageous, and generation of the novel oligosaccharides was achieved by subsequent reductive amination. The target saccharide structures feature a bridging nitrogen atom inserted between two non-anomeric positions as well as including one anomeric position.

Full text of DOI:10.1002/ejoc.200901106

FULL PAPER
DOI: 10.1002/ejoc.200901106
Synthesis of Amino-Bridged Oligosaccharide Mimetics
Janna Neumann[a] and Joachim Thiem*[a]
Keywords: Carbohydrate mimetics / Reductive amination / Oxidation / Oligosaccharides / Bridging ligands / Natural killer
cell
Synthesis of amino-bridged oligosaccharides using reductive
amination opens rapid access to novel glycomimetic target
structures as potential ligands for the receptor protein NKR
P1 of natural killer cells. Emphasis was laid on fast and facile
synthetic routes. The carbonyl building blocks were easily
obtained by oxidation with Dess–Martin periodinane or
iodoxybenzoic acid (IBX). For the required amino-function-
alized units, reduction of azide precursors was advantageous,
and generation of the novel oligosaccharides was achieved
by subsequent reductive amination. The target saccharide
structures feature a bridging nitrogen atom inserted between
two non-anomeric positions as well as including one anom-
eric position.
Introduction
The importance of carbohydrates in biological recogni-
tion processes increased in the last few decades. In particu-
lar, research focused on carbohydrate cell-cell communica-
tion, in which complex glycoconjugates are of great inter-
est.[1] Initial biological studies require mainly simple mi-
metics of complex natural carbohydrate structures for po-
tential drug design as well as for the investigation of glyco-
conjugate-structure relationship in biochemical processes.[2]
The role of carbohydrates as ligands for the receptor pro-
tein of the natural killer cell has been intensely studied.[3–5]
As the natural killer cell is able to kill specific tumor cell
lines,[6] the investigation of the ligand-receptor relationship
is of utmost importance. The receptor protein NKR P1 of
the natural killer cell was demonstrated to belong to the
family of C-type lectin-like proteins which have a carbo-
hydrate recognition domain.[7,8] For investigation of NK
cell resistant tumor cells potential carbohydrate ligands
were tested for their affinity to NKR P1.[9,10] Whereas com-
plex carbohydrate synthesis often requires multiple-step
pathways, rather facile accesses to glycomimetics are of
interest for investigation of carbohydrate–protein interac-
tions. These glycomimetics are mostly non-natural carbo-
hydrate-derived structures that imitate the function of the
natural derivative.[11]
Figure 1. General synthetic scheme.
Emphasis was laid on classical chemical synthesis, how-
ever, mostly avoiding complex protective group chemistry.
By using selective chemical synthesis the unnatural pseudo-
oligosaccharides could be provided in a few facile and high
yielding steps.
Unnatural linkages could be established in different
ways.[12,13] In this contribution formation of the linkage was
realized by using reductive amination[14,15] that selectively
connects aldehydes or ketones with primary or secondary
amines. For reduction of the imine sodium cyanoborohyd-
ride was applied[16] that easily forms the amino-linked di-
saccharide mimetics under very mild conditions.
Results and Discussion
Oxidation
Aim of this work was the synthesis of non-natural oligo-
saccharides using N-acetylhexosamine derivatives as build-
ing blocks. The structures were linked either through glyco-
sidic or non-glycosidic amino bridges and expected to
mimic natural O-glycosidic bonds as well as to provide new
and unnatural pseudo-oligosaccharides. (Figure 1).
As previously described[17] Dess–Martin oxidation is a
mild and selective method to obtain 6-carbaldehydes from
unprotected glycosides, however, the yields could not be en-
hanced to more than 50% (Scheme 1).
Therefore, as another oxidation reagent IBX (iodoxy-
benzoic acid), the precursor of the Dess–Martin
periodinane, was employed. As reported IBX in DMSO
shows about the same oxidative properties as
periodinane.[18,19] Thus preparation of aldehydes 9 and 10
[a] University of Hamburg, Faculty of Science, Department of
Chemistry,
Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
900
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Synthesis of Amino-Bridged Oligosaccharide Mimetics
benzylation of 15 and 16 followed by ring opening using
sodium cyanoborohydride. The partially protected saccha-
rides 19[25] and 20[26] obtained could be easily oxidized with
periodinane and gave the desired products in 74% and 40%
yield, respectively. These 3- and 4-keto sugars can now be
employed as carbonyl building blocks for reductive amin-
ation to link sugar units by amino bridges.
Scheme 1. Oxidation of glycosides with DMP or IBX: a) 1.2 equiv.
DMP, DCM, MeCN, room temp., 2 h; b) 1.5 equiv. IBX, DMSO,
room temp., 2 h.
Amino-Functionalized Building Blocks
The easiest method for preparation of glycosylamines
was reported by Kochetkov et al.[27,28] N-Acetylglucosamine
23 was transformed into glycosylamine 24 by reaction with
saturated ammonium hydrogen carbonate solution, how-
ever, this glycosylamine is rather labile in aqueous media.
Therefore, an alternative route was chosen using the acety-
lated glycosyl azide 25[29] as precursor, which could be hy-
drogenated with palladium on charcoal in 94% yield to give
the corresponding acetylated glycosylamine 26 (Scheme 3).
with IBX provided 33 and 77% yield, which shows IBX to
be as selective as the periodinane but more effective. The
reaction of 10 was monitored using RP-HPLC. According
to these data Dess–Martin oxidation took 35 min and was
much faster, than oxidation with IBX (2 h). In case of the 3-
and 4-keto sugars preparation was achieved by using Dess–
Martin periodinane exclusively (Scheme 2).
Scheme 3. Synthesis of glycosylamines: a) satd. NH4HCO3 solu-
tion, 37 °C, 80 h; b) 1. AcCl, room temp., 16 h, 2. NaN3, DMF,
80 °C, 2 h; c) H2, Pd/C, EtOAc, room temp., 72 h.
These building blocks can be used for preparation of
novel oligosaccharide derivatives comprising the anomeric
center.
For preparation of non-natural oligosaccharides 2-ami-
no- and 6-amino-functionalized saccharides were synthe-
sized as well as 2,6-diamino- and 2,4-diamino-saccharides
(Scheme 4).
Scheme 2. Synthesis of keto sugars: a) 1. PivCl, DCM, pyridine,
0 °C, 2 h, 2. Dess–Martin periodinane, DCM, room temp., 24 h; b)
benzaldehyde dimethyl acetal, THF, pTsA, 80 °C, 20 h; c) Dess–
Martin periodinane, DCM, room temp., 24 h; d) 1. BnBr, NaOH/
DMSO (1:10), room temp., 16 h, 2. NaCNBH3, HCl, THF, room
temp., 30 min.
The partially protected saccharides could be oxidized in
good to very good yields. Treatment of glycosides 5[20] and
11[21] with pivaloyl chloride gave the partially protected gly-
cosides[22,23] which could be oxidized with Dess–Martin
periodinane in dichloromethane to give 4-keto sugars 13
and 14 in 87 and 85% yield, respectively. En route to the 3-
keto sugars 17 and 18, AllGlcNAc 5 and 1,5-anhydro-gluci-
tol 12[24] were transformed into the corresponding benzyl-
idene-protected sugars which were oxidized with Dess–
Scheme 4. Synthesis of diamino sugars: a) 2  NaOH, 100 °C, 16 h;
b) TfN3, DCM, MeOH, DMAP, room temp., 16 h; c) 1. CCl4,
Ph3P, pyridine, 0 °C, 2. 50 °C, 20 min, 3. MeOH, 50 °C, 20 min; d)
NaN3, DMF, 120 °C, 24 h; e) Ba(OH)2·8H2O, H2O, 120 °C, 3 h; f)
H2, Pd/C, MeOH, room temp., 72 h; g) 1. Tf2O, DCM, pyridine,
–35 °C Ǟ 0 °C, 4 h, 2. NaN3, DMF, 80 °C, 3.5 h; h) 1. Ba(OH)2·
8H2O, H2O, 110 °C, 16 h, 2. H2, Pd/C, MeOH, room temp., 72 h.
Employing the diazo transfer with triflyl azide to the 2-
Martin periodinane in dichloromethane in 95% and 59% amino component 27 led to the 2-azido sugar 28 in 42%
yield. Preparation of 4-keto sugars 20 and 21 started with yield. The primary hydroxy group of component 5 could be
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J. Neumann, J. Thiem
FULL PAPER
selectively transformed into the halide 29 in 77% yield using
carbon tetrachloride with triphenylphosphane in pyr-
idine.[30,31] The halide 29 could be easily substituted with
sodium azide in DMF to give the corresponding azide 30
in 60% yield, and deprotection of the acetyl group gave the
2-amino-6-azido-saccharide 31 in 83% yield. Upon hydro-
genation the corresponding diamino-sugar 32 was obtained
with the allyl group transformed to a propyl group.
For preparation of a 2,4-diamino-functionalized saccha-
ride the partially protected anhydro glucitol 33 was reacted
to give the 4-triflate and without further purification trans-
ferred into the epimeric galacto azide 34 in 60% yield over
two steps. This in turn was transferred into the diamino
component 35 in 80% yield.
Scheme 6. Reductive amination II: a) NaCNBH3, MeOH, pH = 6,
room temp., 20 h.
Reductive Amination
duction of ketones to alcohols at pH lower than 6 and pH
higher than 8 leaving the optimum range for reductive
amination with NaCNBH3.[16]
For linking the prepared aldehydo- and amino-function-
alized saccharide building blocks reductive amination with
sodium cyanoborohydride in aqueous methanol at pH 6
and room temperature could be employed.[17] The 2,6-N-
linked structures 37–40 (Scheme 5) could be obtained in Conclusions
average to good yields without attempts for optimization.
These results demonstrate a fast and facile way to pre-
An example of an amino-bridged structure comprising
the anomeric center is the 1,6-N-linked structure 41
(Scheme 5). Carbaldehyde 10 was converted with glycosyl-
amine 24 to give the disaccharide 41 in 23% yield. Again,
compared to the 2,6-N-linked structures this disaccharide
shows lower stabilities as also evident from the lower yield
obtained. The transfer to 6,6-N-linked pseudo-disaccha-
rides could be accomplished with carbaldehyde 10 and allyl
2-acetamido-6-amino-2,6-dideoxy-α--glucopyranoside (42)
(Scheme 6). These structures provide another new unnatu-
ral form of N-linked disaccharides.
Another new N-linkage displays the 3,6-N-linked
pseudo-disaccharide 45 obtained by reaction of 3-keto
sugar 18 with 6-amino sugar 43. In addition a small amount
of the gulo-diastereomere was detected as well as both re-
duction products of keto sugar 18. These results show that
the standard reductive amination used for other linkages
could not be applied here. However, optimization required
pare unnatural oligosaccharide mimetics by using reductive
amination. The aldehyde and keto sugars could be prepared
under very mild and selective conditions with Dess–Martin
periodinane. However, the synthesis of aldehydes was more
effective if the oxidation was carried out with IBX. The
amino-building blocks could be obtained by various meth-
ods. The easiest way is the synthesis of glycosylamines by
Kochetkov et al.[27] Another route proceeds by reduction
of azide precursors to the corresponding amines. Diamino
sugars open access to novel higher oligosaccharides if con-
verted with a carbaldehyde by reductive amination. This
method displays an easy and fast approach to novel N-
linked oligosaccharides to be tested as ligands for the recep-
tor protein NKR P1 of natural killer cells.
Experimental Section
General Remarks: TLC was performed on aluminum sheets coated
is restricted by conditions to be adjusted between the re- with silica gel 60 (Merck) and UV detection by heating with H2SO4
Scheme 5. Reductive amination I: a) NaCNBH3, MeOH, H2O, pH 6, room temp., 20 h; b) NaCNBH3, THF, pH 6, room temp., 20 h.
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Synthesis of Amino-Bridged Oligosaccharide Mimetics
(10% in EtOH). Aldehydes were detected by heating with 2,4-dini-
trophenylhydrazine (0.2  HCl) and amino-functionalized com-
pounds with ninhydrin (0.2  EtOH). Column chromatography
was carried out on silica gel 60 (0.04–0.063 mm; Merck), and gel
permeation chromatography on Sephadex LH20 with doubly dis-
tilled water/methanol (1:1). NMR spectra were recorded with a
Allyl 2-Deoxy-2-phthalimido-β-D-gluco-hexodialdo-1,5-pyranoside
(7): Compound 2[33] (1.279 g, 3.662 mmol) was suspended in aceto-
nitrile (20 mL) and Dess–Martin periodinane (1.863 g, 4.395 mmol,
1.2 equiv.) in dichloromethane (30 mL) added. The reaction mix-
ture was stirred for 2 h at room temperature, then concentrated
and the residue was purified by column chromatography [toluene/
Bruker AMX-400 NMR (13C: 100 MHz) or a DRX-500 NMR acetone (5:1Ǟ3:1Ǟ1:1)]. Product 7 (447 mg, 37%) could be ob-
spectrometer (13C: 125 MHz) and analyzed with solvent peaks as
references. Mass spectra were recorded with a Bruker Biflex II
tained as a colorless solid; m.p. 172.1 °C. [α]2D5 = –41.7 (c = 0.72,
acetone), RF = 0.31 (toluene/acetone, 1:1). 1H NMR (500 MHz,
(MALDI-TOF, positive reflection mode, matrix: 2,5-dihydroxyben- D2O): δ = 8.00–7.86 (m, 4 H, CH-Phth), 5.71 (dddd, JCH-All,=CH2t
zoic acid) and with a VG Analytical 70–250S mass spectrometer
(FAB mass spectra, m-nitrobenzyl alcohol). Melting points were
determined with an Apotec melting point apparatus and are uncor-
rected. The optical rotations were measured with a Perkin–Elmer
341 polarimeter at 20 °C (546 nm, Hg) or a Kruess P8000 polari-
meter at 25 °C (589 nm, Na).
= 17.2, JCH-All,=CH2c = 11.0, JCH-All,-CH2-All = 4.2, JCH-All,-CH2-All =
6.5 Hz, 1 H, CH-All), 5.39–5.29 (m, 2 H, 1-H, 6-H), 5.17 (dd, 1 H,
=CH2-All), 5.09 (dd, 1 H, =CH2-All), 4.43–4.28 (m, 2 H, 3-H,
2
-CH2-All), 4.15 (dd, J-CH2-All,-CH2-All = 12.9 Hz, 1 H, CH2-All),
4.05 (dd, J1,2 = 8.6, J2,3 = 10.7 Hz, 1 H, 2-H), 3.66 (dd, J3,4 = 8.7,
J4,5 = 9.9 Hz, 1 H, 4-H), 3.59 (dd, J5,6 = 2.3 Hz, 1 H, 5-H) ppm.
13C NMR (101 MHz, D2O): δ = 135.2 (CH-Phth) ppm. 133.0
(=CH-All), 118.7 (=CH2-All), 97.6 (C-1), 88.0 (C-6), 76.8 (C-5),
71.1 (C-3), 70.6 (OCH2-All), 70.5 (C-4), 56.7 (C-2) ppm.
C17H17NO7 (347.32) MALDI-TOF-MS: m/z = 369.4 [M + Na]+,
385.4 [M + K]+.
Oxidation General Procedure 1a: The monosaccharide (1.0 mmol)
was suspended in acetonitrile (7.0 mL). A solution of Dess–Martin
periodinane (1.2 mmol) in dichloromethane (10 mL) was added
and stirred for 2 h at room temperature. The reaction mixture was
diluted with dichloromethane/water (1:1) and the organic layer ex-
tracted with water. The aqueous layer was neutralized with a 2.0 
sodium hydroxide solution and concentrated. The residue was puri-
fied by column chromatography.
Allyl 2-Acetamido-2-deoxy-β-D-gluco-hexodialdo-1,5-pyranoside (8):
Compound 3[20] (353 mg, 1.35 mmol) was suspended in acetonitrile
(8 mL) and treated with Dess–Martin periodinane (688.9 mg,
1.625 mmol) in dichloromethane (12 mL) after general procedure
1a. The residue was purified by column chromatography [DCM/
MeOH (8:1)] and product 8 (52.8 mg, 15%) could be obtained as
a colorless solid; m.p. 170.5 °C, [α]2D5 = –14.5 (c = 0.355, DMSO),
RF = 0.19 (DCM/MeOH, 5:1). 1H NMR (400 MHz, D2O): δ =
Oxidation General Procedure 1b: The monosaccharide (1 mmol)
was dissolved in dichloromethane (10 mL). A solution of Dess–
Martin periodinane (1.2 mmol) in dichloromethane (10 mL) was
added and stirred for 2–24 h at room temperature. Sodium thiosul-
fate solution was added to the reaction mixture (4 g/100 mL H2O)
until two distinct phases were established. The organic layer was
neutralized with sodium hydrogen carbonate, washed with water,
dried, and concentrated. The residue was purified by column
chromatography.
5.92 (dddd, JCH-All,=CH2t
=
17.3, JCH-All,=CH2c
=
10.6,
JCH-All,CH2-All = 5.1, JCH-All,CH2-All = 6.2 Hz, 1 H, CH-All), 5.36–
5.24 (m, 3 H, 2ϫ =CH2-All, 6-H), 4.57 (d, J1,2 = 8.5 Hz, 1 H, 1-
2
H), 4.36 (dd, JOCH2-All,OCH2-All = 13.3 Hz, 1 H, -CH2-All), 4.17
(dd, 1 H, -CH2-All), 3.73 (dd, J2,3 = 9.6 Hz, 1 H, 2-H), 3.60–3.50
(m, 2 H, 3-H, 4-H), 3.39 (dd, J4,5 = 9.5, J5,6 = 2.1 Hz, 1 H, 5-H),
2.04 (s, 3 H, CH3-NHAc) ppm. 13C NMR (101 MHz, D2O): δ =
139.4 (=CH-All), 118.1 (=CH2-All), 100.4 (C-1), 88.0 (C-6), 76.5
(C-5), 73.7 (C-3), 70.5 (OCH2-All), 70.4 (C-4), 55.4 (C-2), 22.2
(CH3-NHAc) ppm. C11H17NO6 (259.26) ESI-MS: m/z = 541 [2M
+ Na]+.
Reductive Amination General Procedure 2: Water was added drop-
wise to a solution of aldehyde (0.27 mmol) in methanol (1.5 mL)
and amine (0.68 mmol, 2.5 equiv.) in methanol (1 mL) until com-
plete dissolution. The pH of the solution was adjusted to 6 using
either a 1  solution of glacial acetic acid or a solution of 10%
triethylamine in methanol. Then a 0.3  sodium cyanoborohydride
solution in methanol (0.6 mL) was added and the mixture stirred
at room temperature overnight. The solution was concentrated and
the residue was purified by gel permeation chromatography on Se-
phadex LH20 [water/methanol, (1:1)].
Allyl 2-Acetamido-2-deoxy-α-D-manno-hexodialdo-1,5-pyranoside
(9): 1.) IBX oxidation: Compound 4[34] (133 mg, 0.510 mmol) was
dissolved in DMSO (2.5 mL) und IBX (211 mg, 0.763 mmol) was
added. The reaction mixture was stirred for 2 h at room tempera-
ture, then diluted with water and filtered. The water was removed
by freeze drying and the residue purified by column chromatog-
raphy [DCM/MeOH (10:1)]. Product 9 (43 mg, 33%) could be ob-
tained as a colorless solid. 2.) Dess–Martin oxidation: compound
4[34] (340 mg, 1.30 mmol) was dissolved in acetonitrile (9 mL) and
Dess–Martin periodinane (663 mg, 1.56 mmol) as well as dichloro-
methane (11 mL) added. The reaction mixture was treated for 2 h
according to general procedure 1a. The residue was purified by
column chromatography [DCM/MeOH (12:1)]. Product 9 (91 mg,
Benzyl 2-Deoxy-2-phthalimido-β-D-gluco-hexodialdo-1,5-pyranoside
(6): Compound 1[32] (1.0 g, 2.5 mmol) was suspended in acetonitrile
(15 mL) and Dess–Martin periodinane (1.27 g, 3.02 mmol) in
dichloromethane (20 mL) added. The mixture was stirred for 3 h
at room temperature and then concentrated until dryness. The resi-
due was purified by column chromatography [toluene/acetone
(5:1Ǟ3:1Ǟ1:1)]. Product 6 (386 mg, 39%) could be obtained as a
colorless solid; m.p. 148.4 °C. [α]2D5 = –86.8 (c = 1.01, acetone), RF
1
= 0.40 (ethyl acetate). H NMR (400 MHz, [D6]acetone/D2O): δ =
7.89–7.76 (m, 4 H, CH-Phth), 7.07–6.96 (m, 5 H, CH-Bn), 5.21 (d,
J5,6 = 2.4 Hz, 1 H, 6-H), 5.16 (d, J1,2 = 8.6 Hz, 1 H, 1-H), 4.78 (d,
2JCH2-Bn,CH2-Bn = 12.5 Hz, 1 H, CH2-Bn), 4.54 (d, 1 H, CH2-Bn),
4.25 (dd, J2,3 = 10.7, J3,4 = 8.8 Hz, 1 H, 3-H), 3.98 (dd, 1 H, 2-H),
3.62 (dd, J4,5 = 9.8 Hz, 1 H, 4-H), 3.40 (dd, 1 H, 5-H) ppm. 13C
27%) could be isolated as a colorless solid; m.p. 110 °C. [α]2D4
=
+32.2 (c = 0.115, MeOH), RF = 0.32 (DCM/MeOH, 5:1). 1H NMR
(400 MHz, D2O): δ = 5.98 (dddd, JCH-All,=CH2t = 17.3, JCH-All,=CH2c
= 10.5, JCH-All,-CH2-All = 5.4, JCH-All,-CH2-All = 6.3 Hz, 1 H, CH-
All), 5.39 (dd, 1 H, =CH2-All), 5.35–5.26 (m, 2 H, =CH2-All, 6-
NMR (101 MHz, [D6]acetone/D2O): δ = 135.5 (CH-Phth), 129.0, H), 4.91 (s, J1,2 = 1.4 Hz, 1 H, 1-H), 4.36 (dd, J2,3 = 4.7 Hz, 1 H,
2
128.6, 128.5 (CH-Bn), 124.1 (CH-Phth), 98.6 (C-1), 90.0 (C-6), 77.9
2-H), 4.25 (dd, J-CH2-All,-CH2-All = 12.8 Hz, 1 H, -CH2-All), 4.13–
(C-5), 72.4 (C-4), 71.7 (CH2-Bn), 71.6 (C-3), 57.9 (C-2) ppm. 3.97 (m, 2 H, -CH2-All, 3-H), 3.72–3.61 (m, 2 H, 4-H, 5-H), 2.06
C21H19NO7 (396) ESI-MS: m/z = 420 [M + Na]+, 817 [2M + (s, 3 H, CH3-NHAc) ppm. 13C NMR (101 MHz, D2O): δ = 133.2
Na]+.
(=CH-All), 118.5 (=CH2-All), 98.2 (C-1), 87.9 (C-6), 73.4 (C-5),
903
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J. Neumann, J. Thiem
FULL PAPER
69.2 (C-3), 68.2 (OCH2-All), 67.5 (C-4), 52.5 (C-2), 21.9 (CH3-
NHAc) ppm. C11H17NO6 (259.26) FAB-MS: m/z = 260.1 [M +
H]+. FAB-HRMS: found: 260.1135, calcd. 260.1134 [M + H]+.
4.77 (d, 1 H, CH2-Bn), 4.70–4.64 (m, 2 H, 5-H, 6a-H), 4.49 (dd,
J5,6b = 6.9, 2J6a,6b = 12.7 Hz, 1 H, 6b-H), 2.08 (s, 3 H, CH3-NHAc),
1.39 (s, 9 H, CH3-Piv), 1.38 (s, 9 H, CH3-Piv) ppm. 13C NMR
(101 MHz, CDCl3): δ = 196.1 (C-4), 178.5 (CO-Piv), 169.7 (CO-
NHAc), 129.1 (CH-Bn), 96.9 (C-1), 74.1 (C-3), 72.5 (C-5), 70.9
(CH2-Bn), 61.8 (C-6), 53.6 (C-2), 39.3 [C(CH3)3], 39.2 [C(CH3)3],
27.6, 27.4 [2ϫ C(CH3)3], 23.5 (CH3-NHAc) ppm. C25H35NO8
(477.5) MALDI-TOF-MS: m/z = 478.0 [M + H]+, 500.0 [M +
Na]+, 516.0 [M + K]+.
Allyl
2-Acetamido-2-deoxy-α-D-gluco-hexodialdo-1,5-pyranoside
(10): AllGlcNAc 5[20] (107.6 mg, 0.4123 mmol) was dissolved in
DMSO (2.0 mL) and IBX (174 mg, 0.629 mmol) added. The reac-
tion mixture was stirred for 2 h at room temperature. The reaction
was diluted with water and the precipitate filtered. The water was
removed by freeze drying and the residue purified by column
chromatography [DCM/MeOH (12:1)]. Product 10 (82.7 mg, 77%)
could be isolated as a colorless solid; m.p. 126–129 °C. [α]2D0 = +133
Allyl 2-Acetamido-4,6-O-benzylidene-2-deoxy-α-
D-ribo-hexopyran-
oside-3-ulose (17): Compound 15[25] (500 mg, 1.43 mmol) was sus-
(c = 0.505, MeOH), RF = 0.29 (DCM/MeOH, 5:1). 1H NMR pended in dry dichloromethane (10 mL) and Dess–Martin
(400 MHz, D2O): δ = 5.97 (dddd, JCH-All,=CH2t = 17.3, JCH-All,=CH2c periodinane (915 mg, 2.16 mmol, 1.5 equiv.) in dry dichlorometh-
= 10.7, JCH-All,CH2-All = 5.2, JCH-All,CH2-All = 6.2 Hz, 1 H, CH-All), ane (15 mL) was added. The reaction mixture was treated for 3 h
5.36 (dd, 1 H, =CH2-All), 5.31–5.23 (m, 2 H, =CH2-All, 6-H), 4.97 according to general procedure 1b and the residue was purified by
2
(d, J1,2 = 3.5 Hz, 1 H, 1-H), 4.24 (dd, JOCH2-All,CH2-All = 13.1 Hz,
1 H, -CH2-All), 4.04 (dd, 1 H, CH2-All), 3.91 (dd, J2,3 = 10.7 Hz,
1 H, 2-H), 3.78 (dd, J3,4 = 8.9 Hz, 1 H, 3-H), 3.67 (dd, J4,5 = 10.0,
column chromatography (petroleum ether/ethyl acetate, 1:3). Prod-
uct 17 (474 mg, 95%) could be obtained as a colorless solid; m.p.
188.5 °C. [α]2D5 = +125.1 (c = 1.075, DMSO), RF = 0.27 (petroleum
J5,6 = 1.8 Hz, 1 H, 5-H), 3.56 (dd, 1 H, 4-H), 2.05 (s, 3 H, CH3- ether/ethyl acetate, 1:3). 1H NMR (400 MHz, CDCl3): δ = 7.53–
NHAc) ppm. 13C NMR (101 MHz, D2O): δ = 174.5 (CO-NHAc),
133.6 (=CH-All), 117.8 (=CH2-All), 96.1 (C-1), 87.9 (C-6), 72.8 (C- = 7.9 Hz, 1 H, NH), 5.84 (dddd, JCH-All,=CH2t = 17.0, JCH-All,=CH2c
7.49 (m, 2 H, CH-Bn), 7.38–7.35 (m, 3 H, CH-Bn), 6.28 (d, J2,NH
5), 70.8 (C-3), 70.7 (C-4), 68.4 (OCH2-All), 53.5 (C-2), 21.8 (CH3-
NHAc) ppm. C11H17NO6 (259.26) FAB-MS: m/z = 260.1 [M +
H]+. FAB-HRMS: found: 260.1128, calcd. 260.1134 [M + H]+.
= 10.2, JCH-All,-CH2-All = 5.4, JCH-All,-CH2-All = 6.4 Hz, 1 H, CH-
All), 5.59 (s, 1 H, PhCHOO), 5.38 (d, J1,2 = 4.3 Hz, 1 H, 1-H),
4
5.31–5.21 (m, 2 H, =CH2-All, =CH2-All), 4.98 (ddd, J2,4
=
1.3 Hz, 1 H, 2-H), 4.42–4.37 (m, 2 H, 4-H, 6a-H), 4.18 (dd,
2J-CH2-All,-CH2-All = 12.5 Hz, 1 H, -CH2-All), 4.13 (ddd, J4,5 = 9.9,
J5,6a = 4.8, J5,6b = 2.0 Hz, 1 H, 5-H), 4.04–3.92 (m, 2 H, 6b-H,
-CH2-All), 2.08 (s, 3 H, CH3-NHAc) ppm. 13C NMR (101 MHz,
CDCl3): δ = 195.5 (C-3), 170.5 (CO-NHAc), 133.1 (=CH-All),
129.3 (CH-Bn), 126.8 (CH-Bn), 118.9 (=CH2-All), 102.4
(PhCHOO), 100.6 (C-1), 83.0 (C-4), 69.8 (C-6), 69.4 (-CH2-All),
66.7 (C-5), 59.3 (C-2), 23.5 (CH3-NHAc) ppm. C18H21NO6 (347.4)
MALDI-TOF-MS: m/z = 348.1 [M + H]+, 370.0 [M + Na]+, 386.0
[M + K]+.
Allyl 2-Acetamido-2-deoxy-3,6-di-O-pivaloyl-α-D-xylo-hexopyran-
oside-4-ulose (13): Allyl 2-acetamido-2-deoxy-3,6-di-O-pivaloyl-α-
-glucopyranoside[22] (1.52 g, 3.50 mmol) was dissolved in dry
dichloromethane (15 mL) and Dess–Martin periodinane (1.81 g,
4.20 mmol) dissolved in dichloromethane (20 mL) added. The reac-
tion mixture was treated according to general procedure 1b. The
residue was purified by column chromatography [petroleum ether/
ethyl acetate (1:1)] and product 13 (1.30 g, 87%) could be isolated
20
as a colorless amorphous solid. [α] = +116.7 (c = 0.15, CHCl3),
546
RF = 0.25 (petroleum ether ether/ethyl acetate, 1:1). 1H NMR
(400 MHz, CDCl3): δ = 5.90–5.81 (m, 1 H, CH-All), 5.79 (d, JNH,2 2-Acetamido-1,5-anhydro-4,6-O-benzylidene-2-deoxy-D-ribo-hex-3-
= 9.2 Hz, 1 H, NH), 5.42 (d, 1 H, 3-H), 5.27 (dd, JCH-All,=CH2t
=
ulose (18): Compound 16[26] (300 mg, 1.02 mmol) was suspended in
dichloromethane (15 mL) and Dess–Martin periodinane (526 mg,
1.24 mmol, 1.22 equiv.) in dichloromethane (18 mL) was added.
2
17.2, J=CH2c,=CH2t
= 1.5 Hz, 1 H, =CH2-All), 5.22 (dd,
JCH-All,=CH2c = 10.2 Hz, 1 H, =CH2-All), 5.00 (d, J1,2 = 3.3 Hz, 1
H, 1-H), 4.68 (ddd, J2,3 = 11.7 Hz, 1 H, 2-H), 4.46 (dd, J5,6a = 3.1, The reaction mixture was treated for 16 h according to general pro-
2J6a,6b = 11.8 Hz, 1 H, 6aH), 4.41 (dd, J5,6b = 6.1 Hz, 1 H, 5-H),
cedure 1b and the residue was purified by column chromatography
4.27–4.18 (m, 2 H, 6b-H, -CH2-All), 4.08–4.02 (m, 1 H, -CH2-All), [ethyl acetate]. Product 18 (175 mg, 59%) could be obtained as a
1.91 (s, 3 H, CH3-NHAc), 1.20 (s, 9 H, CH3-Piv), 1.15 (s, 9 H,
colorless solid; m.p. 241 °C (dec.). [α]2D4 = +14.2 (c = 0.69, ethyl
acetate), RF = 0.36 (ethyl acetate). H NMR (400 MHz, CDCl3): δ
1
CH3-Piv) ppm. 13C NMR (101 MHz, CDCl3): δ = 196.2 (C-4),
178.5 (CO-Piv), 178.4 (CO-Piv), 169.8 (CO-NHAc), 133.0 (=CH- = 7.57–7.47 (m, 2 H, CH-Bn), 7.43–7.33 (m, 3 H, CH-Bn), 6.40 (d,
All), 119.4 (=CH2-All), 96.8 (C-1), 74.0 (C-3), 72.4 (C-5), 69.5 JNH,2 = 5.2 Hz, 1 H, NH), 5.60 (s, 1 H, PhCHOO), 4.82 (ddd, J1a,2
2
(OCH2-All), 61.9 (C-6), 53.6 (C-2), 39.3 [C(CH3)3], 39.2 [C(CH3)3], = 7.4, J1b,2 = 8.9 Hz, 1 H, 2-H), 4.72 (dd, J1a,1b = 10.5 Hz, 1 H,
27.6, 27.5, 27.4 [3ϫ C(CH3)3], 23.9 (CH3-NHAc) ppm. C21H33NO8 1a-H), 4.50–4.39 (m, 2 H, 4-H, 6a-H), 3.90 (dd, J5,6b = 10.1, 2J6a,6b
(427.5) MALDI-TOF-MS: m/z = 450.4 [M + Na]+, 466.3 [M +
= 10.6 Hz, 1 H, 6b-H), 3.67 (ddd, J4,5 = 9.8, J5,6a = 4.8 Hz, 1 H,
5-H), 3.31 (dd, 1 H, 1b-H), 2.06 (s, 3 H, CH3-NHAc) ppm. 13C
NMR (101 MHz, CDCl3): δ = 197.2 (C-3), 170.2 (CO-NHAc),
129.4, 128.3, 126.3 (CH-Bn), 101.9 (PhCHOO), 82.9 (C-4), 75.4
(C-5), 72.4 (C-1), 69.3 (C-6), 56.5 (C-2), 23.0 (CH3-NHAc) ppm.
C15H17NO5 (291.30) FAB-MS: m/z = 292.1 [M + H]+. FAB-
HRMS: found: 292.1175, calcd. 292.1185 [M + H]+.
K]+.
Benzyl
2-Acetamido-2-deoxy-3,6-di-O-pivaloyl-α-D-xylo-hexopyr-
anoside-4-ulose (14): Benzyl 2-acetamido-2-deoxy-3,6-di-O-pival-
oyl-α--glucopyranoside[23] (1.11 g, 2.31 mmol) was dissolved in
dry dichloromethane (15 mL) and Dess–Martin periodinane
(1.18 g, 2.78 mmol) in dichloromethane (20 mL) was added. The
reaction mixture was treated according to general procedure 1b and
the residue was purified by column chromatography [DCM/ethyl
Allyl 2-Acetamido-3,6-di-O-benzyl-2-deoxy-α-
D-xylo-hexopyran-
oside-4-ulose (21): Compound 19[25] (260 mg, 0.589 mmol) was dis-
acetate (3:1)]. Product 14 (0.93 g, 85%) could be isolated as a color- solved in dichloromethane (11 mL) and Dess–Martin periodinane
less solid; m.p. 58.2 °C. [α]2D5 = +112 (c = 1.04, CHCl3), RF = 0.46
(DCM/ethyl acetate, 3:1). H NMR (400 MHz, CDCl3): δ = 7.57– action mixture was treated for 20 h according to general procedure
(292 mg, 0.689 mmol) in dichloromethane (12 mL) added. The re-
1
7.49 (m, 5 H, CH-Bn), 5.85 (d, JNH,2 = 9.7 Hz, 1 H, NH), 5.66 (d,
J2,3 = 11.7 Hz, 1 H, 3-H), 5.27 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.99
(d, JCH2Bn,CH2Bn = 11.5 Hz, 1 H, CH2-Bn), 4.90 (ddd, 1 H, 2-H),
1b and the residue purified by column chromatography [petroleum
ether/ethyl acetate (1:2)]. Product 21 (191 mg, 74%) could be iso-
lated as an amorphous solid. [α]2D5 = +98.9 (c = 0.09, CHCl3), RF
2
904
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 900–908

Synthesis of Amino-Bridged Oligosaccharide Mimetics
= 0.42 (petroleum ether ether/ethyl acetate, 1:4). 1H NMR
(400 MHz, CDCl3): δ = 7.39–7.30 (m, 10 H, CH-Bn), 5.89 (dddd,
JCH-All,=CH2t = 17.2, JCH-All,=CH2c = 10.4, JCH-All,-CH2-All = 5.2,
solid; m.p. 148.3 °C (dec.). [α]2D5 = –1.29 (c = 1.085, MeOH), RF
=
0.57 (ethyl acetate/propanol/water, 1:6:3). 1H NMR (400 MHz,
MeOD): δ = 5.16 (dd, J2,3 = 10.3, J3,4 = 9.4 Hz, 1 H, 3-H), 4.96
JCH-All,-CH2-All = 6.4 Hz, 1 H, CH-All), 5.40 (d, JNH,2 = 9.0 Hz, 1 (dd, J4,5 = 9.8 Hz, 1 H, 4-H), 4.31–4.16 (m, 2 H, 1-H, 6a-H), 4.09
2
H, NH), 5.30–5.20 (m, 2 H, 2ϫ =CH2-All), 5.10 (d, J1,2 = 3.5 Hz,
(dd, J5,6b = 2.3, J6a,6b = 12.2 Hz, 1 H, 6b-H), 3.88–3.68 (m, 2 H,
1 H, 1-H), 4.94 (d, 1 H, CH2-Bn), 4.65–4.55 (m, 3 H, 2-H, 2ϫ 2-H, 5-H), 2.04 (s, 3 H, CH3-Ac), 2.00 (s, 3 H, CH3-Ac), 1.98 (s, 3
2
CH2-Bn), 4.47 (d, JCH2-Bn,CH2-Bn = 12.0 Hz, 1 H, CH2-Bn), 4.53 H, CH3-Ac), 1.92 (s, 3 H, CH3-NHAc) ppm. 13C NMR (101 MHz,
( dd, J5 , 6 a = 3 . 6, J5 , 6 b = 6 . 3 H z , 1 H , 5 - H ) , 4 . 2 5 ( d d ,
MeOD): δ = 172.4 (CO-Ac), 86.1 (C-1), 75.0 (C-3), 73.9 (C-5), 70.6
2J-CH2-All,-CH2-All = 12.9 Hz, 1 H, -CH2-All), 4.13–4.05 (m, 2 H, 3- (C-4), 63.8 (C-6), 56.2 (C-2), 22.8 (CH3-NHAc), 20.6 (3ϫ CH3-
2
H, -CH2-All), 3.96 (dd, J6a,6b = 10.8 Hz, 1 H, 6a-H), 3.73 (dd, 1
H, 6b-H), 1.95 (s, 3 H, CH3-NHAc) ppm. 13C NMR (101 MHz,
CDCl3): δ = 201.5 (C-4), 133.1 (=CH-All), 128.4–127.7 (CH-Bn),
118.3 (=CH2-All), 96.4 (C-1), 79.3 (C-3), 73.8 (C-5), 73.7 (CH2-
Bn), 72.5 (CH2-Bn), 69.0 (-CH2-All), 67.7 (C-6), 54.1 (C-2), 23.3
(CH3-NHAc) ppm. C25H29NO6 (439.5) MALDI-TOF-MS: m/z =
462.5 [M + Na]+, 478.5 [M + K]+.
Ac) ppm. C14H22N2O8 (346.33) MALDI-TOF-MS: m/z = 347.0 [M
+ H]+, 369.0 [M + Na]+, 384.9 [M + K]+.
Allyl 2-Azido-2-deoxy-α-D
-glucopyranoside (28): AllGlcNAc 5[20]
(500 mg, 1.92 mmol) was suspended in 2  sodium hydroxide
(18 mL) and stirred overnight at 100 °C. After cooling to room
temperature the reaction mixture was neutralized with 2  hydro-
chloric acid, filtered through silica, and eluted with ethyl acetate/
MeOH/H2O (7:2:1) The filtrate was concentrated and the remain-
ing water removed by freeze drying. The obtained amine was dis-
solved in methanol (20 mL) and DMAP (464 mg, 3.80 mmol) as
well as freshly prepared triflyl azide (4.22 mmol) in dichlorometh-
ane (0.4 ) added. The reaction was stirred for 16 h at room tem-
perature then concentrated, and the residue was purified by column
chromatography (DCM/MeOH, 8:1). Product 28 (0.196 g, 42%)
could be isolated as a yellow oil. [α]2D5 = +136.3 (c = 0.405, MeOH),
RF = 0.53 (DCM/MeOH, 5:1). 1H NMR (400 MHz, MeOD):
δ = 5.96 (dddd, JCH-All,=CH2t = 17.3, JCH-All,=CH2c = 10.5,
JCH-All,CH2-All = 5.7, JCH-All,CH2-All = 5.0 Hz, 1 H, CH-All), 5.36
2-Acetamido-1,5-anhydro-3,6-di-O-benzyl-2-desoxy-D-xylo-hex-4-
ulose (22): Compound 20[26] (480 mg, 1.25 mmol) was dissolved in
dry dichloromethane (10 mL) and Dess–Martin periodinane
(634 mg, 1.49 mmol) in dichloromethane (12 mL) added. The reac-
tion mixture was treated for 3 h according to general procedure
1b and the residue purified by column chromatography (petroleum
ether/ethyl acetate, 1:50). Product 22 (193 mg, 40%) could be iso-
lated as an amorphous solid. [α]2D0 = +23.1 (c = 0.065, CHCl3), RF
1
= 0.40 (ethyl acetate). H NMR (400 MHz, CDCl3): δ = 7.42–7.31
(m, 10 H, CH-Bn), 5.39 (d, JNH,2 = 5.6 Hz, 1 H, NH), 4.88 (d, 1
H, CH2 -Bn), 4.65–4.53 (m, 2 H, 2 ϫ CH2 -Bn), 4.47 (d,
2JCH2Bn,CH2Bn = 11.8 Hz, 1 H, CH2-Bn), 4.32 (dd, J1a,2 = 4.5, 2J1a,1b
= 11.7 Hz, 1 H, 1a-H), 4.15–4.05 (m, 3 H, 2-H, 3-H, 5-H), 3.88
(dd, 1 H, =CH2-All), 5.16 (dd, 1 H, =CH2-All), 4.93 (d, J1,2
=
2
3.5 Hz, 1 H, 1-H), 4.24 (dd, JCH2-All,CH2-All = 13.2 Hz, 1 H, -CH2-
All), 4.04 (dd, 1 H, -CH2-All), 3.81–3.79 (m, 2 H, 3-H, 6a-H), 3.68
(dd, J5,6b = 5.5, 2J6a,6b = 11.9 Hz, 1 H, 6b-H), 3.59 (ddd, J4,5 = 9.8,
J5,6a = 2.1 Hz, 1 H, 5-H), 3.35 (dd, J3,4 = 8.9 Hz, 1 H, 4-H), 3.10
(dd, J2,3 = 10.4 Hz, 1 H, 2-H) ppm. 13C NMR (101 MHz, MeOD):
δ = 135.2 (=CH-All), 117.4 (=CH2-All), 98.6 (C-1), 74.0 (C-5), 72.6
(C-3), 72.2 (C-4), 69.3 (OCH2-All), 64.6 (C-2), 62.5 (C-6) ppm. IR:
2
(dd, J5,6a = 3.5, J6a,6b = 10.9 Hz, 1 H, 6aH), 3.77–3.68 (m, 2 H,
1bH, 6b-H), 1.89 (s, 3 H, CH3-NHAc) ppm. 13C NMR (101 MHz,
CDCl3): δ = 128.8, 127.9 (CH-Bn), 81.1 (C-5), 80.2 (C-3), 72.9,
72.5 (CH2-Bn), 68.2 (C-6), 67.4 (C-1), 54.0 (C-2), 23.1 (CH3-
NHAc) ppm. C22H25NO5 (383.44) MALDI-TOF-MS: m/z = 405.5
[M + Na]+, 421.5 [M + K]+.
ν = -N -valency (2105 ) cm–1. C H N O (245.23) FAB-MS: m/z
˜
3
9
15
3
5
= 246.1 [M + H]+. FAB-HRMS: found: 246.1081, calcd. 246.1090
2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl Azide
[M + H]+.
(25): 2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-α--glucopyranosyl
chloride[24] (2.0 g, 5.5 mmol) was dissolved in DMF (14 mL) and
sodium azide (0.94 g, 0.085 mol) was added. The reaction mixture
was stirred for 2 h at 50 °C. The mixture was diluted with chloro-
form and washed with water several times. The organic layer was
dried, concentrated and the residue was purified by column
chromatography (ethyl acetate). The product 25 (1.6 g, 79%) could
be obtained as a colorless solid; m.p. 161 °C (m.p.[29] 166–167 °C).
[α]2D0 = –18.9 (c = 0.55, CHCl3), RF = 0.32 (ethyl acetate). 1H NMR
(400 MHz, CDCl3): δ = 5.76 (d, JNH,2 = 8.9 Hz, 1 H, NH), 5.46
(dd, J2,3 = 10.7, J3,4 = 9.4 Hz, 1 H, 3-H), 5.32 (dd, J4,5 = 9.9 Hz,
1 H, 4-H), 4.97 (d, J1,2 = 9.2 Hz, 1 H, 1-H), 4.49 (dd, J5,6a = 4.8,
2J6a,6b = 12.5 Hz, 1 H, 6a-H), 4.39 (dd, J5,6b = 2.3 Hz, 1 H, 6b-H),
4.13 (ddd, 1 H, 2-H), 4.00 (ddd, 1 H, 5-H), 2.32 (s, 3 H, CH3-Ac),
2.26 (2ϫ s, 6 H, 2 ϫ CH3-Ac), 2.20 (s, 3 H, CH3-NHAc) ppm. 13C
NMR (101 MHz, CDCl3): δ = 170.3 (CO-Ac), 88.4 (C-1), 74.1 (C-
5), 72.1 (C-3), 68.0 (C-4), 61.8 (C-6), 54.3 (C-2), 23.2 (CH3-NHAc),
20.7, 20.6, 20.5 (3 ϫ CH3-OAc) ppm. C14H20N4O8 (372.33)
Allyl 2-Acetamido-6-chloro-2,6-dideoxy-α-D-glucopyranoside (29):
AllGlcNAc 5[20] (1.0 g, 3.8 mmol) was dissolved in pyridine
(30 mL) and triphenylphosphane (2.26 g, 8.55 mmol) was added.
At 0 °C carbon tetrachloride (3.7 mL, 38 mmol, 5.8 g) was slowly
and dropwise added and then stirred for 20 min at 50 °C. For ter-
mination of the reaction methanol (5 mL) was added and stirring
continued for 20 min at 50 °C. The mixture was concentrated and
the residue, after co-distillation with toluene, purified by column
chromatography (ethyl acetate/MeOH, 20:1Ǟ15:1Ǟ10:1). Product
29 (818 mg, 77 %) could be obtained as a yellow solid; m.p.
154.5 °C, [α]2D5 = +146 (c = 0.815, MeOH), RF = 0.45 (DCM/
MeOH, 5:1) 1H NMR (400 MHz, MeOD): δ = 5.94 (dddd,
J=CH-All,=CH2t = 17.2, J=CH-All,=CH2c = 10.5, J=CH-All,OCH2-All = 5.1,
J=CH-All,OCH2-All = 6.1 Hz, 1 H, CH-All), 5.32 (dd, 1 H, =CH2-All),
5.19 (dd, 1 H, =CH2-All), 4.83 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.21
2
(dd, JOCH2-All,OCH2-All = 13.1 Hz, 1 H, -CH2-All), 4.02 (dd, 1 H,
-CH2-All), 3.92 (dd, J2,3 = 10.7 Hz, 1 H, 2-H), 3.87 (dd, J5,6a = 1.6,
2J6a,6b = 11.3 Hz, 1 H, 6a-H), 3.80–3.63 (m, 3 H, 3-H, 5-H, 6b-H),
3.36 (dd, J3,4 = 8.9, J4,5 = 9.3 Hz, 1 H, 4-H), 1.98 (s, 3 H, CH3-
NHAc) ppm. 13C NMR (101 MHz, MeOD): δ = 174.1 (CO-
NHAc), 135.7 (=CH-All), 118.1 (=CH2-All), 98.1 (C-1), 73.7 (C-
4), 73.6 (C-5), 73.0 (C-3), 69.6 (OCH2-All), 55.7 (C-2), 46.1 (C-6),
22.9 (CH3-NHAc) ppm. C11H18ClNO5 (279.72) FAB-MS: m/z =
280.1 [M + H]+. FAB-HRMS: found: 280.0950, calcd. 280.0952 [M
+ H]+.
MALDI-TOF-MS: m/z = 394.9 [M + Na]+, 410.9 [M + K]+. IR: ν
˜
= 2103 cm–1 (N3 valency).
2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosylamine
(26): Azide 25 (400 mg, 1.07 mmol) was dissolved in ethyl acetate
(20 mL) under argon. To the solution was added Pd/C (2 spatula
tips) and stirred for 72 h at room temperature under hydrogen. The
catalyst was filtered through sodium sulfate and the filtrate concen-
trated. The product 26 (347.5 mg, 94%) was obtained as a colorless
Eur. J. Org. Chem. 2010, 900–908
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
905

J. Neumann, J. Thiem
-glucopyranoside (30): 2-Acetamido-1,5-anhydro-4-azido-2,4-dideoxy-3,6-di-O-pivaloyl-D-
FULL PAPER
Allyl 2-Acetamido-6-azido-2,6-dideoxy-α-
D
Compound 29 (807 mg, 2.89 mmol) was dissolved in DMF
(12 mL), sodium azide (958 mg, 14.7 mmol) was added and the re-
action mixture was stirred for 24 h at 120 °C. After cooling to room
temperature the solid was filtered and washed with acetonitrile. The
filtrate was concentrated and the residue purified by column
chromatography (ethyl acetate/MeOH, 15:1). Product 30 (498 mg,
galactitol (34): Compound 33[22] (1.50 g, 4.28 mmol) was dissolved
under argon in dry dichloromethane (35 mL) and dry pyridine
(2.0 mL). Trifluoromethane sulfuric acid anhydride (0.85 mL,
5.1 mmol) was slowly added at –35 °C and the reaction was stirred
for 4 h at 0 °C. The mixture was diluted with dichloromethane and
washed with 2.5  hydrochloric acid. The organic layer was neu-
tralized with saturated sodium hydrogen carbonate solution,
washed with water, dried and concentrated.
60%) could be obtained as a colorless solid; m.p. 117.4 °C. [α]2D5
=
+97.9 (c = 0.19, MeOH), RF = 0.33 (ethyl acetate/MeOH, 10:1).
1H NMR (400 MHz, MeOD): δ = 5.59 (dddd, JCH-All,=CH2t = 17.2,
JCH-All,=CH2c = 10.4, JCH-All,CH2-All = 5.2, JCH-All,CH2-All = 6.1 Hz,
The residue was dissolved in DMF (13 mL) sodium azide (1.3 g,
20 mmol) added and stirred for 3.5 h at 80 °C. The reaction mixture
was diluted with chloroform and washed with water. The organic
layer was dried, concentrated and the residue purified by column
chromatography (petroleum ether ether/ethyl acetate, 1:2). Product
34 (1.03 g, 60 %) could be obtained as a colorless solid; m.p.
119.8 °C. [α]2D0 = –52.6 (c = 1.01, CHCl3), RF = 0.33 (petroleum
ether ether/ethyl acetate, 1:4). 1H NMR (400 MHz, CDCl3): δ =
1 H, CH-All), 5.33 (dd, 1 H, =CH2-All), 5.20 (dd, 1 H, =CH2-All)
2
4.85 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.21 (dd, JOCH2-All,OCH2-All
13.1 Hz, 1 H, -CH2-All), 4.03 (dd, 1 H, -CH2-All), 3.96 (dd, J2,3
=
=
10.7 Hz, 1 H, 2-H), 3.75 (ddd, J4,5 = 9.8, J5,6a = 2.3, J5,6b = 6.6 Hz,
2
1 H, 5-H), 3.66 (dd, J3,4 = 8.8 Hz, 1 H, 3-H), 3.51 (dd, J6a,6b
=
13.2 Hz, 1 H, 6a-H), 3.41 (dd, 1 H, 6b-H), 3.34 (dd, 1 H, 4-H),
1.99 (s, 3 H, CH3-NHAc) ppm. 13C NMR (101 MHz, MeOD): δ =
173.7 (CO-NHAc), 135.3 (=CH-All), 117.8 (=CH2-All), 97.7 (C-
1), 73.2 (C-4), 73.1 (C-5), 72.6 (C-3), 69.5 (OCH2-All), 55.3 (C-2),
5.49 (d, J2,NH = 8.3 Hz, 1 H, NH), 5.06 (dd, J2,3 = 10.8, J3,4
=
3.5 Hz, 1 H, 3-H), 4.48 (dddd, J1a,2 = 5.3, J1b,2 = 11.0 Hz, 1 H, 2-
2
H), 4.24 (dd, J5,6a = 6.3, J6a,6b = 11.3 Hz, 1 H, 6a-H), 4.19–4.07
52.8 (C-6) 22.5 (CH -NHAc) ppm. IR: ν = -N -valency (2096 )
˜
3
3
(m, 2 H, 1a-H, 6b-H), 3.89 (dd, J4,5 = 1.5 Hz, 1 H, 4-H), 3.67 (ddd,
cm–1. C11H18N4O5 (286.28) FAB-MS: m/z = 287.1 [M + H]+. FAB-
2
J5,6b = 6.5 Hz, 1 H, 5-H), 3.10 (dd, J1a,1b = 11.1 Hz, 1 H, 1b-H),
HRMS: found: 287.1355, calcd. 287.1356 [M + H]+.
1.91 (s, 3 H, CH3-NHAc), 1.25 (s, 9 H, CH3-Piv), 1.21 (s, 9 H,
CH3-Piv) ppm. 13C NMR (101 MHz, CDCl3): δ = 179.4, 178.0 (2ϫ
CO-Piv), 169.9 (CO-NHAc), 75.2 (C-5), 73.4 (C-3), 68.8 (C-1), 62.9
(C-6), 61.1 (C-4), 47.0 (C-2), 39.3 [C(CH3)3], 27.1, 26.9 [C(CH3)3],
23.1 (CH3-NHAc) ppm. C18H30N4O6 (398.45) MALDI-TOF-MS:
Allyl 2-Acetamido-2-amino-6-azido-2,6-dideoxy-α-D-glucopyran-
oside (31): Compound 30 (731 mg, 2.55 mmol) and barium hydrox-
ide octahydrate (10.5 g, 33.3 mmol) in water (50 mL) were stirred
for 3 h at 120 °C. After cooling to room temperature the reaction
mixture was stirred for 24 h. The solid was filtered and the filtrate
was extracted continuously until no product was detected in the
aqueous phase. The organic phase was dried and the solvents evap-
orated in vacuo. Product 31 (515 mg, 83%) could be obtained as a
yellow oil. [α]2D5 = +127 (c = 0.165, MeOH), RF = 0.30 (ethyl
acetate/MeOH/water, 7:3:1). 1H NMR (400 MHz, MeOD): δ =
5.98 (dddd, J=CH-All,=CH2t = 17.2, J=CH-All,=CH2c = 10.4,
J=CH-All,OCH2-All = 5.3, J=CH-All,OCH2-All = 6.1 Hz, 1 H, CH-All),
5.36 (dd, 1 H, =CH2-All), 5.20 (dd, 1 H, =CH2-All), 4.86 (d, J1,2
m/z = 399.1 [M + H]+, 421.1 [M + Na]+, 437.0 [M + K]+. IR: ν =
˜
2104 cm–1 (N3 valency).
2,4-Diamino-1,5-anhydro-2,4-dideoxy-D-galactitol (35): Compound
34 (771 mg, 1.94 mmol) and barium hydroxide octahydrate (5.24 g,
16.6 mmol) in water were stirred overnight at 110 °C. After cooling
to room temperature, the precipitate was filtered and the water was
removed by freeze drying. The residue was diluted with a small
amount of water and the mixture treated with dry ice to remove
the barium salts. The solvent was again removed by freeze drying.
The residue was diluted in methanol (4 mL) and Pd/C (one spatula
tip) added. The mixture was stirred under hydrogen for 72 h at
room. Then the catalyst was filtered through sodium sulfate and
the filtrate was concentrated. The residue was purified by gel per-
meation chromatography on Sephadex LH20 (MeOH/water, 1:1).
Product 35 (253 mg, 80%) could be obtained as a colorless solid;
m.p. 220 °C (dec.). [α]2D0 = +16 (c = 0.05, water), RF = 0.34 (BuOH/
2
= 3.6 Hz, 1 H, 1-H), 4.25 (dd, JOCH2-All,OCH2-All = 12.9 Hz, 1 H,
-CH2-All), 4.04 (dd, 1 H, -CH2-All), 3.73 (ddd, J4,5 = 9.8, J5,6a
=
2.3, J5,6b = 5.5 Hz, 1 H, 5-H), 3.52–3.37 (m, 3 H, 3-H, 6a-H, 6b-
H), 3.24 (dd, J3,4 = 8.9 Hz, 1 H, 4-H), 2.63 (dd, J2,3 = 10.0 Hz, 1
H, 2-H) ppm. 13C NMR (101 MHz, MeOD): δ = 134.2 (=CH-All),
115.9 (=CH2-All), 97.8 (C-1), 74.6 (C-3), 71.8 (C-5), 71.2 (C-4),
68.0 (OCH -All), 55.7 (C-2), 51.4 (C-6) ppm. IR: ν = -N -valency
˜
2
3
(2099 ) cm–1. C9H16N4O4 (244.25) FAB-MS: m/z = 245.1 [M +
1
H]+. FAB-HRMS: found: 245.1252, calcd. 245.1250 [M + H]+.
AcOH/water, 5:2:2). H NMR (400 MHz, D2O): δ = 3.94–3.82 (m,
2 H, 1a-H, 3-H), 3.76–3.63 (m, 3 H, 5-H, 6a-H, 6b-H), 3.59–3.47
Propyl 2,6-Diamino-2,6-dideoxy-α-D-glucopyranoside (32): Azide 31
(m, 2 H, 1b-H, 4-H), 3.05 (ddd, J1a,2 = 5.3, J1b,2 = 10.8, J2,3
=
(107.8 mg, 0.4414 mmol) was dissolved in methanol (6 mL) and Pd/
CaCO3 (one spatula point) was added. The reaction mixture was
stirred under hydrogen for 72 h at room temperature. After reaction
has terminated the catalyst was filtered off over Celite and the fil-
trate was concentrated. The residue was purified by gel permeation
10.2 Hz, 1 H, 2-H) ppm. 13C NMR (101 MHz, D2O): δ = 78.1 (C-
5), 68.4 (C-3), 61.6 (C-6), 61.3 (C-1), 52.6 (C-2), 46.1 (C-4) ppm.
C6H14N2O3 (162.19) FAB-MS: m/z = 201.0 [M + K]+.
N-(Benzyl 2,6-dideoxy-2-phthalimido-β-
-glucitol-2-yl)amine (37): Aldehyde 6
(90.7 mg, 0.229 mmol) in methanol (2 mL) and amine 36[17]
D-glucopyranoside-6-yl)-
chromatography on Sephadex LH20 (MeOH/water, 1:1). Product (1,5-anhydro-2-deoxy-
D
32 (19.6 mg, 20%) could be isolated as an amorphous solid. [α]2D5
1
= +50 (c = 0.08, water), RF = 0.53 (DCM/MeOH, 5:1). H NMR (114 mg, 0.569 mmol) in methanol (1 mL) were treated according
(500 MHz, D2O): δ = 5.18 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 3.99–3.86
(m, 2 H, 4-H, 5-H), 3.72 (ddd, JOCH2-Pr,OCH2-Pr = 12.2 Hz, 1 H,
to general procedure 2. After purification by gel permeation
chromatography on Sephadex LH20 (methanol/water, 1:1) product
37 (45 mg, 36 %) could be obtained as a colorless solid; m.p.
2
OCH2-Pr), 3.55–3.34 (m, 4 H, OCH2-Pr, 2-H, 3-H, 6a-H), 3.19 (dd,
2
J5,6b = 8.9, J6a,6b = 13.4 Hz, 1 H, 6b-H), 1.71–1.58 (m, 182.1 °C. [α]2D5 = –21.4 (c = 0.575, MeOH), RF = 0.36 (ethyl acetate/
1
JOCH2-Pr,CH2-Pr = 2.8, JOCH2-Pr,CH2-Pr = 6.7 Hz, 2 H, CH2-Pr), 0.94 MeOH/water, 7:3:1). H NMR (400 MHz, [D6]acetone): δ = 7.91–
(t, 3 H, CH3-Pr) ppm. 13C NMR (125 MHz, D2O): δ = 94.9 (C-1),
7.73 (m, 4 H, CH-Phth), 7.14–7.02 (m, 5 H, CH-Bn), 5.19 (d, J1,2
2
71.2 (C-3), 70.2 (OCH2-Pr), 69.2, 68.7 (C-4, C-5), 53.6 (C-2), 49.4
= 8.6 Hz, 1 H, 1-H), 4.79 (d, JCH2-Bn,CH2-Bn = 12.4 Hz, 1 H, CH2-
(C-6), 21.8 (CH2-Pr) ppm. C9H20N2O4 (220.27) ESI-MS: m/z = 243 Bn), 4.57 (d, 1 H, CH2-Bn), 4.27 (dd, J2,3 = 10.7, J3,4 = 8.6 Hz, 1
[M + Na]+.
H, 3-H), 4.07–3.99 (m, 2 H, 1aЈH, 2-H), 3.80 (dd, J5Ј,6aЈ = 2.8,
906
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 900–908

Synthesis of Amino-Bridged Oligosaccharide Mimetics
2J6aЈ,6bЈ = 11.7 Hz, 1 H, 6aЈH), 3.66–3.58 (m, 2 H, 5-H, 6bЈ-H), (methanol/water, 1:1) product 40 (25 mg, 14%) could be isolated as
3.41 (dd, J4,5 = 9.3 Hz, 1 H, 4-H), 3.34–3.28 (m, 2 H, 3Ј-H, 4Ј-H), a colorless solid; m.p. 133 °C. [α]2D5 = +124 (c = 0.11, MeOH), RF
1
3.17 (ddd, J4Ј,5Ј = 8.8, J5Ј,6bЈ = 5.6 Hz, 1 H, 5Ј-H), 3.14–3.05 (m, 2 = 0.70 (iPrOH/NH3/H2O, 5:1:2). H NMR (400 MHz, D2O): δ =
2
H, 1bЈ-H, 6a-H), 2.90 (dd, J5,6b = 7.1, J6a,6b = 13.2 Hz, 1 H, 6b- 6.13–5.84 (m, 2 H, 2ϫ CH-All), 5.48–5.23 (m, 4 H, 4ϫ =CH2-
H), 2.65 (ddd, J1aЈ,2Ј = 4.8, J1bЈ,2Ј = 9.4, J2Ј,3Ј = 10.4 Hz, 1 H, 2Ј-
H) ppm. 13C NMR (101 MHz, [D6]acetone): δ = 135.1 (CH-Phth),
128.9, 128.4, 128.2 (CH-Bn), 122.8 (CH-Phth), 98.5 (C-1), 82.2 (C-
5Ј), 78.0 (C-3Ј), 74.9 (C-5), 74.2 (C-4), 72.4 (C-4Ј), 72.1 (C-3), 71.2
All), 5.11 (d, J1Ј,2Ј = 3.7 Hz, 1 H, 1Ј-HЈ), 4.93 (d, J1,2 = 3.4 Hz, 1
H, 1-H), 4.32–4.21 (m, 2 H, 2ϫ -CH2-All), 4.16–4.04 (m, 2 H, 2ϫ -
CH2-All), 4.00–3.91 (m, 2 H, 2-H, 3ЈH), 3.81–3.72 (m, 3 H, 3-H,
5-H, 5Ј-H), 3.43–3.33 (m, 3 H, 4-H, 4Ј-H, 6aЈ-H), 3.21–3.06 (m, 3
2
(CH2-Bn), 70.0 (C-1Ј), 63.2 (C-6Ј), 59.6 (C-2Ј), 58.3 (C-2), 48.7 (C- H, 6a-H, 2Ј-H, 6bЈ-H), 2.91 (dd, J5,6b = 4.5, J6a,6b = 12.7 Hz, 1
6) ppm. C20H35N5O9 (544.55) MALDI-TOF-MS: m/z = 544.9 [M
H, 6b-H), 2.05 (s, 3 H, CH3-NHAc) ppm. 13C NMR (101 MHz,
D2O): δ = 133.5 (=CH-All), 118.1 (=CH2-All), 96.1 (C-1), 95.9 (C-
1Ј), 72.2 (C-4 ppm. C-4Ј), 71.8 (C-3), 70.7 (C-5, C-5Ј), 68.1 (C-3Ј),
54.4 (C-2Ј), 53.6 (C-2), 49.0 (C-6Ј), 47.6 (C-6), 22.0 (CH3-NHAc)
+ H]+, 566.9 [M + Na]+, 584.9 [M + K]+.
N-(Allyl 2,6-dideoxy-2-phthalimido-β-D-glucopyranoside-6-yl)-(1,5-
anhydro-2-deoxy- -glucitol-2-yl)amine (38): Aldehyde 7 (94 mg,
D
ppm. IR: ν = -N -valency (2102 ) cm–1. C20H35N5O9 (487.50)
˜
3
0.27 mmol) in methanol (2 mL) and amine 36[17] (134.6 mg,
0.676 mmol) in methanol (1 mL) were treated according to general
procedure 2. After purification by gel permeation chromatography
on Sephadex LH20 (methanol/water, 1:1) product 38 (95 mg, 71%)
could be isolated as a colorless solid; m.p. 236 °C. [α]2D5 = +11.1 (c
MALDI-TOF-MS: m/z = 483.9 [M + Na – N2]+.
N-(Allyl 2-acetamido-2,6-dideoxy-α-
D-glucopyranoside-6-yl)-(2-
acetamido-2-deoxy-β- -glucopyranosyl)amine (41): Compound 10
D
(100 mg, 0.386 mmol) was suspended in THF (3 mL) and amine
1
= 0.28, MeOH), RF = 0.40 (ethyl acetate/MeOH/water, 7:3:1). H
24[27] (380 mg, 1.73 mmol) in THF (5 mL) added. The pH was ad-
NMR (400 MHz, D2O): δ = 7.97–7.73 (m, 4 H, CH-Phth), 5.65 justed to 6 by adding 1  acetic acid solution dropwise. Then a
(dddd, JCH-All,=CH2t = 17.1, JCH-All,=CH2c = 10.3, JCH-All,-CH2-All
=
0.3  solution of sodium cyanoborohydride in THF (1.0 mL) was
5.2, JCH-All,-CH2-All = 5.9 Hz, 1 H, CH-All), 5.26 (d, J1,2 = 8.6 Hz,
added. The reaction mixture was stirred overnight at room tem-
1 H, 1-H), 5.09 (dd, 1 H, =CH2-All), 5.01 (dd, 1 H, =CH2-All), perature, concentrated and the residue purified by gel permeation
4.33–4.18 (m, 2 H, -CH2-All, 3-H), 4.16–4.01 (m, 2 H, -CH2-All, chromatography on Sephadex LH20 (methanol/water, 1:1). Product
2
1aЈ-H), 3.96 (dd, J2,3 = 9.7 Hz, 1 H, 2-H), 3.82 (dd, J6aЈ,6bЈ
=
40 (41.6 mg, 23 %) could be obtained as a yellow solid; m.p.
20
11.6 Hz, 1 H, 6aЈ-H), 3.72–3.61 (m, 2 H, 5-H, 6bЈ-H), 3.44–3.20 100.5 °C. [α]
= +26 (c = 0.41, H2O), RF = 0.73 (iPrOH/NH3/
546
(m, 5 H, 4-H, 1bЈ-H, 3Ј-H, 4Ј-H, 5Ј-H), 3.12 (dd, J5,6a = 2.7, 2J6a,6b
= 12.1 Hz, 1 H, 6a-H), 2.93–2.72 (m, 2 H, 2Ј-H, 6b-H) ppm. 13C JCHAll,-CH2-All = 5.3 Hz, 1 H, CH-All), 5.15 (dd, 1 H, =CH2-All),
NMR (101 MHz, D2O): δ = 135.2 (CH-Phth), 133.3 (=CH-All), 5.06 (dd, 1 H, =CH2-All), 4.95 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.35
ethyl acetate 5:3:1). 1H NMR (400 MHz, D2O): δ = 5.75 (dddd,
2
123.8 (CH-Phth), 118.7 (=CH2-All), 97.7 (C-1), 80.6 (C-5Ј), 74.0 (d, J1Ј,2Ј = 9.4 Hz, 1 H, 1ЈH), 4.25 (dd, J-CH2-All,-CH-All = 13.2 Hz,
(C-5), 72.4 (C-4, C-4Ј), 70.9 (CH2-All), 70.7 (C-3), 70.3 (C-3Ј), 66.8 1 H, -CH2-All), 4.07 (dd, 1 H, -CH2-All), 3.99–3.36 (m, 12 H, 2-
(C-1Ј), 61.2 (C-6Ј), 57.6 (C-2Ј), 56.9 (C-2), 47.4 (C-6) ppm. H, 2ЈH, 3-H, 3Ј-H, 4-H, 4Ј-H, 5-H, 5Ј-H, 6a-H, 6aЈ-H, 6b-H, 6bЈ-
C20H35N5O9 (494.49) MALDI-TOF-MS: m/z = 516.5 [M + Na]+.
H), 2.05 (s, 6 H, 2 ϫ CH3-NHAc) ppm. 13C NMR (101 MHz,
D2O): δ = 133.7 (=CH-All), 117.9 (=CH2-All) 96.0 (C-1), 85.9 (C-
1Ј), 76.7 (C-5), 74.9 (C-4), 72.4 (C-5Ј), 71.0 (C-3Ј), 70.4 (C-4Ј), 70.3
(C-3), 68.6 (-CH2-All), 61.2 (C-6, C-6Ј), 55.2 (C-2Ј), 53.7 (C-2),
21.9 (CH3-NHAc) ppm. C19H33N3O9 (463.5): MALDI-TOF-MS:
m/z = 502.1 [M + K]+.
N-(Allyl 2-acetamido-2,6-dideoxy-α- -mannopyranoside-6-yl)-(1,5-
D
anhydro-2-deoxy- -glucitol-2-yl)amine (39): Aldehyde 9 (131 mg,
D
0.506 mmol) was dissolved in methanol (2.5 mL) and amine 36[17]
in methanol (1.5 mL) was added. The reaction mixture was treated
according to general procedure 2 and the residue was purified by
gel permeation chromatography (methanol/water, 1:1). Product 39
Propyl 2-Acetamido-6-amino-2,6-dideoxy-α-D-glucopyranoside (43):
(103 mg, 50%) could be isolated as a colorless solid; m.p. 98.5 °C. Compound 30 (493.6 mg, 1.724 mmol) was dissolved in methanol
[α]2D4 = +50.1 (c = 0.715, H2O), RF = 0.27 (ethyl acetate/MeOH/
(22 mL) and Pd/CaCO3 (one spatula point) added. The reaction
H2O, 7:3:1). 1H NMR (400 MHz, D2O): δ = 5.89 (dddd, mixture was stirred under hydrogen for 20 h at room temperature.
JCH-All,=CH2t = 17.3, JCH-All,=CH2c = 10.4, JCH-All,-CH2-All = 5.4,
JCH-All,-CH2-All = 6.1 Hz, 1 H, CH-All), 5.29 (dd, 1 H, =CH2-All),
5.16 (dd, 1 H, =CH2-All), 4.79 (d, J1,2 = 1.3 Hz, 1 H, 1-H), 4.28
(dd, J2,3 = 4.7 Hz, 1 H, 2-H), 4.22–4.12 (m, 2 H, -CH2-All, 1aЈ-H),
The catalyst was filtered through Celite and washed with methanol.
The filtrate was concentrated and the residue purified by column
chromatography [ethyl acetate/MeOH (1:1Ǟ100% MeOH)]. Prod-
uct 43 (370 mg, 82%) could be obtained as a yellow solid; m.p.
4.02 (dd, 2J-CH2-All,-CH2-All = 13.0 Hz, 1 H, -CH2-All), 3.94 (dd, J3,4 128 °C. [α]2D4 = +114 (c = 0.17, MeOH), RF = 0.05 (ethyl acetate/
= 9.8 Hz, 1 H, 3-H), 3.86–3.76 (m, 2 H, 5-H, 6aЈ-H), 3.62 (dd,
MeOH, 1:1). 1H NMR (400 MHz, MeOD): δ = 4.79 (d, J1,2
J5Ј,6bЈ = 5.5, J6aЈ,6bЈ = 10.4 Hz, 1 H, 6bЈ-H), 3.55 (dd, J2Ј,3Ј = 9.9, 3.6 Hz, 1 H, 1-H), 3.87 (dd, J2,3 = 10.7 Hz, 1 H, 2-H), 3.71–3.63
=
2
J3Ј,4Ј = 8.2 Hz, 1 H, 3Ј-H), 3.47–3.27 (m, 5 H, 1bЈ-H, 4Ј-H, 5Ј-H, (m, 2 H, 3-H, OCH2-Pr), 3.55 (ddd, J4,5 = 10.0, J5,6a = 3.0, J5,6b
4-H, 6a-H), 3.15–2.98 (m, 2 H, 2Ј-H, 6b-H), 1.96 (s, 3 H, CH3- 7.2 Hz, 1 H, 5-H), 3.40–3.33 (m, 1 H, OCH2-Pr), 3.22 (dd, J3,4
=
=
NHAc) ppm. 13C NMR (101 MHz, D2O): δ = 174.8 (CO-NHAc),
8.3 Hz, 1 H, 4-H), 2.99 (dd, 2J6a,6b = 13.3 Hz, 1 H, 6a-H), 2.75 (dd,
133.3 (=CH-All), 118.4 (=CH2-All), 98.2 (C-1), 80.5 (C-5Ј), 74.0 1 H, 6b-H), 1.98 (s, 3 H, CH3-NHAc), 1.70–1.57 (m, JCH2-Pr,CH3-Pr
(C-3Ј), 70.2 (C-4Ј), 68.8 (C-3, C-4, C-5), 68.6 (-CH2-All), 65.6 (C-
= 7.4 Hz, 2 H, CH2-Pr), 0.97 (t, 3 H, CH3-Pr) ppm. 13C NMR
1Ј), 60.8 (C-6Ј), 57.7 (C-2Ј), 52.6 (C-2), 46.8 (C-6), 22.0 (CH3- (101 MHz, MeOD): δ = 173.7 (CO-NHAc), 98.5 (C-1), 74.1 (C-4),
NHAc) ppm. C17H30N2O9 (406.43) MALDI-TOF-MS: m/z = 406.8
73.4 (C-5), 72.7 (C-3), 70.7 (OCH2-Pr), 55.6 (C-2), 43.9 (C-6), 23.7
(CH2-Pr), 22.5 (CH3-NHAc), 11.0 (CH3-Pr) ppm. C11H20N2O5
(262.30) FAB-MS: m/z = 263.2 [M + H]+. FAB-HRMS: found:
263.1619, calcd. 263.1607 [M + H]+.
[M + H]+, 428.8 [M + Na]+, 444.8 [M + K]+.
N-(Allyl 2-acetamido-2,6-dideoxy-α-
D-glucopyranoside-6-yl)-(allyl
6-azido-2,6-dideoxy-α- -glucopyranose-2-yl)amine (40): Aldehyde
D
10 (94 mg, 0.36 mmol) in methanol (2 mL) and amine 31 (220 mg, Bis-N-(allyl 2-acetamido-2,6-dideoxy-α-D-glucopyranoside-6-yl)-
0.901 mmol) in methanol (1 mL) were treated according to general
procedure 2. After purification by gel permeation chromatography
amine (44): Aldehyde 10 (102 mg, 0.394 mmol) in methanol (2 mL)
and amine 42[17] (250 mg, 0.954 mmol) in methanol (2 mL) were
Eur. J. Org. Chem. 2010, 900–908
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
907

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FULL PAPER
treated according to general procedure 2. The residue was purified
by gel permeation chromatography on Sephadex LH20 (methanol/
water, 1:1) and product 44 (115 mg, 58%) could be isolated as a
yellow solid; m.p. 230 °C (dec.). [α]2D0 = +123.7 (c = 0.135, H2O),
[3]
[4]
[5]
[6]
1
RF = 0.16 (ethyl acetate/MeOH/H2O, 7:3:1). H NMR (400 MHz,
D2O): δ = 5.97 (dddd, JCH-All,=CH2t = 17.3, JCH-All,=CH2c = 10.4,
JCH-All,-CH2-All = 5.2, JCH-All,-CH2-All = 6.1 Hz, 2 H, 2ϫ CH-All),
5.36 (dd, 2 H, 2 ϫ =CH2-All), 5.28 (dd, 2 H, 2 ϫ =CH2-All),
4.96 (d, J1,2 = J1Ј,2Ј = 3.6 Hz, 2 H, 1-H, 1Ј-H), 4.24 (dd,
2J-CH2-All,-CH2-All = 13.1 Hz, 2 H, 2ϫ -CH2-All), 4.07 (dd, 2 H,
2ϫ -CH2-All), 4.03–3.92 (m, 4 H, 2-H, 2Ј-H, 5-H, 5Ј-H), 3.78 (dd,
[7]
[8]
[9]
[10]
[11]
J2,3 = J2Ј,3Ј = 10.6, J3,4 = J3Ј,4Ј = 8.9 Hz, 2 H, 3-H, 3Ј-H), 3.52–3.33
(m, 4 H, 4-H, 4Ј-H, 6a-H, 6aЈ-H), 3.19 (dd, J6a,6b
K. Bezousˇka, G. Vlahas, O. Horváth, G. Jinochová, A. Fi-
sˇerová, R. Giorda, W. H. Chambers, T. Feizi, M. Pospísˇil, J.
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Y. Chapleur (Ed.), Carbohydrate Mimics, Wiley-VCH,
Weinheim, 1998.
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C. F. Lane, Synthesis 1975, 135–146.
J. C. Gildersleeve, O. Oyelaran, J. T. Simpson, B. Allred, Bi-
oconjugate Chem. 2008, 19, 1485–1490.
2
= =
2J6aЈ,6bЈ
12.1 Hz, 2 H, 6b-H, 6bЈ-H), 2.05 (s, 6 H, 2ϫ CH3-Ac) ppm. 13C
NMR (101 MHz, D2O): δ = 174.5 (2ϫ CO-Ac), 133.6 (2ϫ =CH-
All), 118.0 (2ϫ =CH2-All), 96.2 (C-1, C-1Ј), 72.2 (C-4, C-4Ј), 70.8
(C-3, C-3Ј), 68.8 (2ϫ -CH2-All), 68.0 (C-5, C-5Ј), 53.6 (C-2, C-2Ј),
48.7 (C-6, C-6Ј), 21.9 (2ϫ CH3-Ac) ppm. C22H37N3O10 (503.54)
MALDI-TOF-MS: m/z = 504.4 [M + H]+, 525.4 [M + Na]+, 541.3
[M + K]+.
[12]
[13]
[14]
[15]
N-(Propyl 2-acetamido-2-deoxy-α-
dro-2-acetamido-4,6-O-benzylidene-2-deoxy-
D-glucopyranose-6-yl)-(1,5-anhy- [16]
R. F. Borch, M. D. Bernstein, H. Dupont Durst, J. Am. Chem.
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1130–1144.
M. Frigerio, M. Santagostino, Tetrahedron Lett. 1994, 35,
8019–8022.
D
-glucitol-3-yl)amine
[17]
[18]
(45): Ketone 18 (59.2 mg, 0.203 mmol) in methanol (3 mL) and
amine 43 (137 mg, 0.526 mmol) in methanol (4 mL) were treated
according to general procedure 2. After purification by column
chromatography [DCM/MeOH (9:1)] product 45 (22 mg, 20%)
could be isolated as a colorless solid; m.p. 225.8 °C. [α]2D5 = +34 (c
= 0.36, MeOH), RF = 0.23 (DCM/MeOH/, 5:1). 1H NMR
(400 MHz, D2O): δ = 7.49–7.36 (m, 5 H, CH-Bn), 5.70 (s, 1 H,
PhCHOO), 4.68 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.27 (dd, J5Ј,6aЈ = 5.0,
[19] M. Frigerio, M. Santagostiono, S. Sputore, G. Palmisano, J.
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1958, 611, 236–241.
2J6aЈ,6bЈ = 10.5 Hz, 1 H, 6aЈ-H), 4.07 (ddd, J1bЈ,2Ј = 10.6, J2Ј,3Ј
=
[22] L. Kröger, A. Scudlo, J. Thiem, Adv. Synth. Catal. 2006, 348,
2
1217–1227.
10.3 Hz, 1 H, 2Ј-H), 3.90 (dd, J1aЈ,2 = 5.2, J1aЈ,1bЈ = 11.4 Hz, 1 H,
1aЈ-H), 3.81–3.69 (m, 3 H, 2-H, 4Ј-H, 6bЈ-H), 3.66–3.49 (m, 3 H,
3-H, 5-H, 5Ј-H), 3.46–3.33 (m, 2 H, OCH2-Pr, 1bЈ-H), 3.32–3.12
(m, 3 H, OCH2-Pr, 4-H, 6a-H), 3.06 (dd, J3Ј,4Ј = 9.9 Hz, 1 H, 3Ј-
[23] L. Rochepeau-Jobron, J.-C. Jacquinet, Carbohydr. Res. 1998,
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Chem. 1995, 14, 369–385.
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de Souza, V. F. Feirreira, Nucleosides Nucleotides Nucleic Acids
2001, 20, 1555–1569.
2
H), 2.94 (dd, J5,6b = 8.0, J6a,6b = 11.8 Hz, 1 H, 6b-H), 1.96 (s, 3
H, CH3-NHAc), 1.94 (s, 3 H, CH3-NHAcЈ), 1.48–1.37 (m, 2 H,
CH2-Pr), 0.77 (t, 3 H, CH3-Pr) ppm. 13C NMR (125 MHz, D2O):
δ = 128.5, 125.9 (CH-Bn), 101.2 (PhCHOO), 96.3 (C-1), 79.0 (C-
4Ј), 72.4 (C-4), 71.2 (C-5Ј), 70.7 (C-3), 69.9 (OCH2-Pr), 69.7 (C-5),
68.0 (C-1Ј), 67.7 (C-6Ј), 60.7 (C-3Ј), 53.6 (C-2), 49.2 (C-2Ј), 47.7
(C-6), 21.8, 21.6 (CH3-NHAc), 21.3 (CH2-Pr) ppm. C26H39N3O9
(537.60) FAB-MS: m/z = 538.3 [M + H]+. FAB-HRMS: found:
538.2772, calcd. 538.2765 [M + H]+.
[30] R. L. Whistler, A. K. M. Anisuzzaman, Methods Carbohydr.
Chem. 1980, 8, 227–231.
Acknowledgments
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61, 511–518.
Support of this work by the Fonds der Chemischen Industrie and
the Deutsche Forschungsgemeinschaft (DFG) (SFB 470, A5) is
gratefully acknowledged.
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Received: September 28, 2009
Published Online: December 22, 2009
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