Synthesis of sugar isocyanates and their application to the formation of ureido-linked disaccharides

Article abstract of DOI:10.1002/ejoc.200500601

The present work describes a facile and practical route to carbohydrate-based isocyanates, a reactive and appealing family of chiral heterocumulenes, wich can be easily converted into disaccharides and pseudodisaccharides interconnected by urea moieties.

Full text of DOI:10.1002/ejoc.200500601

FULL PAPER
DOI: 10.1002/ejoc.200500601
Synthesis of Sugar Isocyanates and Their Application to the Formation of
Ureido-Linked Disaccharides[‡]
Martín Ávalos,[a] Reyes Babiano,[a] Pedro Cintas,[a] Michael B. Hursthouse,[b]
José L. Jiménez,[a] Mark E. Light,[b] Juan C. Palacios,*[a] and Esther M. S. Pérez[a]
Dedicated to Professor Joaquín Plumet on the occasion of his 60th birthday
Keywords: Isocyanates / Ureas / Ureidosugars
The present work describes a facile and practical route to
carbohydrate-based isocyanates, a reactive and appealing
family of chiral heterocumulenes, wich can be easily con-
stances by X-ray diffraction analysis and spectroscopic meth-
ods reveals further insights into their structures and preferred
conformation.
verted into disaccharides and pseudodisaccharides intercon- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
nected by urea moieties. A full characterization of these sub-
Germany, 2006)
relevant biological properties such as the antibiotics SF-
1993,[8] CV-1,[9] and the family of glycocinnamoylspermid-
ines.[10] A few glycosylureas have shown to be α-glycosidase
inhibitors[11] and N-nitrosoureas, such as streptozotocin[12]
and chlorozotocin,[13] possess antitumoral activity.[14] These
substances induce crosslinking of DNA after in vivo de-
composition. The generated isocyanate does not appear to
be directly involved in the antitumor effect of nitrosoureas,
but it does react with amines and proteins. More import-
antly, it inhibits DNA polymerase and other enzymes in-
volved in the repair of DNA lesions. It also inhibits RNA
synthesis and plays a role in the toxicity of nitrosoureas.[15]
Strategies for the construction of ureidosugars are rela-
tively scarce and mainly involve the condensation of mono-
saccharides with ureas to give glycosylureas[16] and symmet-
rical ureidodisaccharides.[17] They also involve the reaction
of glycosylamines[18,19] or amino sugars[20–24] with isocya-
nates or their synthetic equivalents such as carbamates,[25,26]
addition of water to diglycosylcarbodiimides,[27,28] as well
as side products in varied transformations of glycosyl isocy-
anates.[26,29]
Introduction
Although the preparation of urea and its derivatives
dates back to the early history of organic synthesis, the
enormous chemical and biological potential of this linkage
has only been recognized and exploited within the last dec-
ades. Thus, urea itself is capable of forming inclusion com-
plexes with long-chain alkanes and some functionalized
molecules.[1,2] In such complexes, the urea molecules self-
assemble through intermolecular hydrogen bonds giving
rise to a helical lattice into which the guest compounds can
be oriented and accommodated. Urea moieties also act as
strong hydrogen-bond donors and acceptors,[3] and have
been frequently used as functional groups for the formation
of supramolecular architectures.[4] Substituted ureas and bis-
ureas have also been shown to give gels with organic liquids
and water,[5] and in some cases the gels are thermally revers-
ible and require very low concentrations.[6]
Some thiourea-linked pseudodisaccharides, O-protected
by acyl groups, have been prepared and structurally charac-
terized.[7] However, the corresponding ureido disaccharides
are seldom known. Some carbohydrate-based ureas exhibit
A convenient synthetic protocol for the construction of
structurally diverse glycoconjugates and pseudooligossach-
arides could be developed by reaction of protected sugar
[‡] Part of this work has been presented at V Jornadas de Carbohi- isocyanates with amino compounds. In this context, pro-
dratos, Badajoz, Spain, 2000, pp. 42; and 1er Congrés Maroco-
tected glycosyl isocyanates have been prepared by reaction
Espagnol sur la Chimie Organique, Marrakech, Morocco, 2004,
of O-protected glycosylamines with phosgene,[30] or its safer
A-124.
synthetic surrogates,[31] e.g. triphosgene[23] or haloform-
[a] Departamento de Química Orgánica, Facultad de Ciencias,
Universidad de Extremadura,
ates,[29] by reaction of glycosyl halides with silver cya-
Avenida de Elvas s/n, 06071 Badajoz, Spain
nate,[32] through sugar phosphanimines,[33] or by oxidation
Fax: +34-924-271-149
of glycosyl isocyanides with pyridine N-oxide.[30,34,35] How-
E-mail: palacios@unex.es
[b] Departament of Chemistry, University of Southampton, High-
ever, only one previous work addresses the preparation of a
field,
Southampton S017 1BJ, UK
monosaccharide isocyanate at a non-anomeric position.[36]
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J. C. Palacios et al.
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Herein, we describe a synthetic methodology for the gen atoms, which in turn indicates that the plane containing
preparation of a wide range of protected sugar isocyanates the enamino group and the mean plane of the pyranose ring
as well as symmetrical and unsymmetrical ureas linking form a dihedral angle of approximately 90° (Figure 1).
non-anomeric carbon atoms.
Results and Discussion
Synthesis of Raw Materials: A series of precursors have
been required toward the synthesis of sugar isocyanates,
such as those derived from amino sugars 1–3 and the ami-
noalditol 4, some of them already described, while other
Figure 1. View of the dihedral angle between the main plain of the
pyranose ring and the enamino group.
substances have been prepared for the first time in this
work. Although O-protected derivatives of 2-amino-2-de-
The remaining coupling constants of the sugar moiety
oxy-d-glucose (1) are well known, the corresponding ana- are likewise consistent with a pyranose ring of α-d-galacto
logs of 2-amino-2-deoxy-d-galactose (2) have seldom been configuration exhibiting a 4C1 conformation. It should also
reported, and therefore we have optimized the preparation be pointed out that the large value of its optical rotation
of 7 and 10.
agrees with an α configuration at the anomeric position.
Finally, a facile and high-yielding N-deprotection could
be accomplished with bromine and water in chloroform[7,38]
giving rise to 7.
The alternative preparation of the β-anomer 10 is de-
picted in Scheme 2. In this case the temporary protection
of the amino group was effected with cinnamaldehyde.
Conversion into the resulting imine 8 is accompanied by a
selective formation of the β-anomer, which was further per-
O-acetylated to give 9, while preserving the stereochemistry
at the anomeric position. After treatment with 5 m HCl in
acetone, the amino group was deprotected. The β-configu-
ration for 8–10 is inferred from the large values of J1,2 coup-
ling constants and the small values of their optical rota-
tions.
The known 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-α-d-
The appropriate protection of an amino group at C-2 as glucopyranose hydrobromide (11)[39] was prepared from 1
an enamino derivative also controls the stereochemistry at following the same route used for 7.
the anomeric position. Thus, the synthesis of 1,3,4,6-tetra-
O-acetyl-2-amino-2-deoxy-α-d-galactopyranose (7) is sum- glucopyranose, 12,[40] 13,[41] 14,[42] as well as of 2-amino-2-
marized in Scheme 1.
deoxy-d-glycero-l-gluco-heptopyranose, 15,[7] and 16,[7]
The condensation of 2 with diethyl ethoxymethylenema- have also been prepared according to literature protocols.
lonate affords exclusively the α-anomer of the enamine 5, We have equally carried out the preparation of the hydro-
A series of precursors derived from 2-amino-2-deoxy-d-
which is subsequently transformed into the per-O-acetylen- bromide derived from per-O-acetyl-d-glucamine (19). Its
amine 6 without affecting the configuration at the anomeric synthesis is no more than a peripheral modification em-
position. Its spectroscopic data are analogous to those of ployed for the synthesis of the hydrochloride,[43] and similar
the enamine derived from 1.[37] The large coupling con- to the route described above for compounds 7 and 11
stants between the NH and 2-H (JNH,2 Ϸ 9–10 Hz) and (Scheme 3). The main, yet relevant, variation is the cleavage
between that NH and the CH= proton (JNH,CH Ϸ 14 Hz) of the enamine intermediate 18 with bromine instead of
clearly suggest an antiperiplanar disposition for such hydro- using a stream of chlorine.
Scheme 1. Reagents: i: EtOCH=C(CO2Et)2, Et3N; ii: Ac2O, C5H5N; iii: Br2, H2O, Cl3CH.
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Sugar Isocyanates and Their Application for Ureido-Linked Disaccharides
FULL PAPER
Scheme 2. Reagents: i: trans-PhCH=CHCHO, NaHCO3; ii: Ac2O, C5H5N; iii: 5 m HCl, CH3COCH3.
Scheme 3. Reagents: i: EtOCH=C(CO2Et)2,Et3N; ii: Ac2O, C5H5N; iii: Br2, H2O, Cl3CH.
Scheme 4. Reagents: i: NH3; ii: EtOCH=C(CO2Et)2, Et3N; iii: Ac2O, C5H5N; iv: Br2, H2O, Cl3CH.
Finally, the enamine strategy has also been used for the involves the addition, under vigorous stirring, of a 1.93 m
synthesis of 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl- solution of phosgene in toluene to a mixture of the corre-
amine hydrobromide (21),[38] starting from the β-d-gluco- sponding amino sugar hydrohalide and pyridine in CH2Cl2
pyranosylamine 20 (Scheme 4), which can be easily ob- at 0 °C. Pyridine can also be replaced by triethylamine with-
tained by the reaction of d-glucose and ammonia.[44]
Syntheses of Sugar Isocyanates: Isocyanates have been
out affecting product yields.
The second protocol (method B), analogous to that em-
frequently employed as building blocks in combinatorial ployed recently by Ichikawa et al. in the synthesis of Fi-
chemistry to generate a library by reaction with amines or scher’s glucopyranosyl isocyanate (31),[23] involves the use
hydroxy groups. Accordingly, the isocyanates 22–31 have of a solid synthetic equivalent of phosgene, triphosgene, un-
been synthesized by treatment of amino sugars 7, 10–16, der heterogeneous conditions similar to those of the
19, and 21 with phosgene (COCl2) or triphosgene (Cl3CO- Schotten–Baumann synthesis. This method is also reminis-
COOCl3). The derivative 25 is the only non-anomeric isocy- cent of the well-established preparation of sugar isothiocy-
anate described so far; it was prepared by Jochims and See- anates using liquid thiophosgene.[7,36,46] Thus, to a solution
liger in 1965 using a stream of phosgene.[36] Given the in- of the corresponding amino sugar hydrohalide and a satu-
herent toxicity and hazards associated with the use of phos- rated solution of sodium hydrogen carbonate was added tri-
gene, a convenient, safer and easy-to-use reagent is a 1.93 m phosgene, under vigorous stirring, at 0 °C in order to mini-
solution of phosgene in toluene, which has been employed mize the potential hydrolysis of the generated isocyanate.
by Norwick and co-workers for the preparation of amino Table 1 collects our results, including the synthesis of 31 for
acid ester isocyanates.[45] Thus, the first strategy (method A) comparative purposes.
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Table 1. Synthesis of sugar isocyanates.
Entry
Precursor
Product
Method[a]
Yield (%)
1
2
3
4
5
6
7
8
9
10
7
22
23
24
25
26[b]
27
28
29
30
31
B
70
10
11
12
13
14
15
16
17
18
A, B
A, B
A, B
A
45, 65
65, 64
51, 96
88
B
37
A, B
A, B
B
55, 52
63, 82
80
A, B
51, 86
[a] Method A (amino sugar/phosgene in toluene); Method B
(amino sugar/triphosgene). [b] Isolated as 32.
The structures and stereochemistries attributed to com-
pounds 22–25, 27–31 are consistent with their spectroscopic
and analytical data, as well as with their optical rotations.
All isocyanates exhibit a strong FT-IR absorption at about
Figure 2. X-ray structure of 30 showing atomic numbering and
thermal ellipsoids at the 50% probability level.
2260 cm–1 and 13C resonances at ca. 126 ppm, which are one 32, (Scheme 6) whose isolated yield should also reflect
typical of the heterocumulene fragment. For compound 27, the extent at which the isocyanate was produced. The ab-
the absorption at 2320 cm–1 is also characteristic of the az- sence of the characteristic IR band at 2260 cm–1 and the
ide group. Moreover, the structure of the acyclic isocyanate N=C=O resonance at δ = 125 ppm, together with the pres-
30 could unambiguously be established by single-crystal dif- ence of the NH absorption at 3300 cm–1, δNH at δ =
fraction analysis and its ORTEP diagram is collected in 6.31 ppm and δNCOO at δ = 156 ppm account for the sug-
Figure 2.[47]
gested structure of imidazolidin-2-one.
For compound 30, an analysis of its proton–proton
The bicyclic derivative 32 has been described previously
coupling constants reveals that this substance should be resulting from diverse reactions of per-O-acetylcarbamates
preferentially existing in solution as an equilibrium between of 1.[49–51] The above-mentioned synthesis is a new and
2G– and G– G+ conformations. An extended zig-zag con- straightforward procedure that gives 32 in high yield, an
2
5
formation (P) or a G– G– conformation would otherwise interesting aspect because such an oxazolidin-2-one could
2
5
cause a strong 1,3-diaxial interaction between the acetate be employed as chiral auxiliary in asymmetric methodolo-
groups located at C-2 and C-4 or C-4 and C-6, respectively gies. Compound 32 could further be characterized by its N-
(Scheme 5).[48] Remarkably, a G– G+ conformation is the acetyl derivative 33.[13] A strong downfield peak for the N-
2
5
preferred geometry adopted by 30 in the crystal lattice (vide acetyl group (δAcN = 2.53 ppm) and the shifted resonances
supra, Figure 2). of 2-H (∆δ2-H = 0.64) and 3-H (∆δ3-H = 0.46), presumably
Compound 26 was generated as a transient species and reflect the deshielding caused by the N-acetyl group and the
intramolecularly trapped by its glucopyranoimidazolidin-2- heterocyclic C=O bond on the most stable conformation.
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Sugar Isocyanates and Their Application for Ureido-Linked Disaccharides
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Scheme 5.
Scheme 6. Reagents: i, Cl2CO, toluene; ii, Ac2O, C5H5N.
This geometry reveals an antiperiplanar disposition be- anose in compounds 34 and 35, whereas the same spacer
tween the carbonyl groups in order to reduce the dipole– links the same position of two 2-amino-2-deoxy-d-gluco-
dipole interaction. This arrangement has also been found pyranose units in 36 and 37.
in 3-acetyl-2-oxazolidones[52] and other five-membered N-
acylated heterocycles,[53–55] and has a marked effect on the
optical rotation causing a significant decrease (Ϸ 60°) going
from 32 to 33.[54,55]
The coupling constant J1,2 exhibit an unusual large value
(Ϸ 7 Hz) for an α-anomer derived from compound 1,
whereas J2,3 (4.2 Hz) and J3,4 (5.3 Hz) have unexpected
small values. Overall, such data suggest a severe distortion
4
of the C1 conformation (characteristic of compounds de-
rived from 1) owing to the cis fusion with the oxazolidin-2-
one ring. The sugar moiety of 32 and 33 should therefore
adopt a preferential 0S2 conformation in solution.[20,41,56] It
should be mentioned that a trans fusion would provide
larger coupling constants (Ϸ 9 Hz).[57]
Syntheses of Ureylenedisaccharides: The facile access to
isocyanates 22–25 and 27–31 offers the possibility of pre-
paring a wide variety of urea-tethered neoglyconjugates,
glycopeptide mimetics, and pseudooligosaccharides with
We should point out that compound 37 had already been
urea and carbamate bonds as the carbohydrate–peptide and prepared by Jochims and Seeliger by treatment of 12 with
carbohydrate–carbohydrate linkages. Probably, the most 25.[36] The molecular symmetry (C2v) present in 34–37 sim-
1
versatile method to synthesize both symmetrical and un- plifies the structural elucidation as both H and 13C NMR
symmetrical carbohydrate-based ureas is the reaction of a spectra exhibit only one signal set for the two sugar moie-
sugar isocyanate with an appropriately protected amino ties.
sugar and, in fact this approach has been assessed through-
out this study.
Likewise, the ureido disaccharides 38 and 39 contain two
residues of 2-amino-2-deoxy-d-glucopyranose, albeit with
Formation of such ureidodisaccharides has been carried different stereochemistry or functionality at the anomeric
out by reacting equimolar amounts of the sugar isocyanate position. The α,α anomers 34 and 36 have larger optical
and the amino sugar hydrohalide in pyridine solution at rotations than their β,β counterparts 35 and 37; as expected
room temperature. This heterocyclic base gives rise to the the α,β ureido derivative 38 exhibits an intermediate value.
free amino sugar, which attacks then the electrophilic isocy-
In compounds 40–42, the urea spacer links two structur-
anate group. There is a set of 55 possible synthetic combina- ally different amino sugars. In all cases, one of the frag-
tions involving the starting isocyanates 22–31 with the ments comes from 2-amino-2-deoxy-β-d-glucopyranose,
amino derivatives 7, 10–16, 19, and 21. However, our study while the other involves either 2-amino-2-deoxy-β-d-galac-
has been focused on 10 representative compounds (34–43). topyranose (40) or 2-amino-2-deoxy-d-glycero-l-gluco-hep-
Thus, an ureido group interconnects the C-2 position of topyranose, having β (41) or α (42) anomeric configura-
two identical fragments of 2-amino-2-deoxy-d-galactopyr- tions. Finally, the symmetrical urea 43 constitutes the first
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J. C. Palacios et al.
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example of this kind of glycoconjugates interconnecting prepared by reaction of 11 and 12 with silver cyanate in
two acyclic amino sugars.
aqueous medium (Scheme 7).
Scheme 7. Reagents: i, AgNCO, H2O.
In addition, the NMR spectra of the sugar fragments
present in the non-symmetrical urea 38 can be considered
a superposition of those of 36 and 37. A similar interpret-
ation facilitates the structural assignment of the non-sym-
metrical derivatives 40–42. Further two-dimensional NMR
correlations, selective decoupling, and proton–deuterium
exchange also corroborated our assessment. Coupling con-
stants suggest that, in solution, the hexopyranose ring
adopts a preferential 4C1 conformation, whereas the 1C4 ar-
rangement is adopted by heptopyranoses. The anomeric
configuration could easily be deduced from such coupling
constants (a large value for β-anomers of hexoses and α-
anomers of heptoses, characteristic of equatorial substitu-
ents, as well as small values for α-anomers in hexoses and
As expected, the proposed structures for compounds 34– β-anomers in heptoses, typical of axial groups); along with
43 can easily be inferred from their spectroscopic and ana- the 13C resonances for the anomeric carbon atoms (a down-
lytical data, and other physical constants. In addition, the field shift is observed with equatorial groups at C-1). It is
solid-state geometry for compound 40 could be determined equally interesting the large value of the coupling constants
by single-crystal X-ray diffractometry (Figure 3).[58]
JCH,NH (ca. 9 Hz), thus evidencing an antiperiplanar dispo-
The NH groups of the ureido group show FT-IR absorp- sition between these protons. Again, the plane containing
tion bands at ca. 3300 and 1540 cm–1, while the urea car- the urea fragment and the mean plane of the pyranose ring
bonyl groups appear at ca. 150 ppm in the 13C NMR spec- should form a dihedral angle of ca. 90°. Scheme 8 depicts
tra. It is interesting to note that both proton and carbon the three possible conformers (Z,Z; Z,E, and E,E) that
resonances of compounds 36 and 37 are nearly coincidental could exist in solution, assuming the above-mentioned anti-
with those of the ureidoanalogs 44[59] and 45,[60] which were periplanar relationship.
Figure 3. X-ray structure of 40 showing atomic numbering and thermal ellipsoids at the 50% probability level.
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Sugar Isocyanates and Their Application for Ureido-Linked Disaccharides
FULL PAPER
Scheme 8.
Because NMR spectra of compounds 34–37 evidence a Table 2. Hydrogen bonds [Å and degrees] in the crystalline state of
the ureidodisaccharide 40.[a]
symmetrical pattern, only Z,Z or E,E conformers may be
observable. However, the latter should be particularly un-
stable due to 1,3-syndiaxial steric interactions. Further-
more, the chemical shift for the 2-H proton (δ2-H Ϸ 4.0–
4.4 ppm) is similar to that of Z-conformers in sugar for-
D–H··A
δ(D–H) δ(H···A)
δ(D···A)
Ͻ(D–H–A)
N1–H1···O10[b]
0.88
0.88
2.40
2.38
3.076(6)
3.201(6)
134.3
154.9
N2–H2···O18[b]
[a] For atom numbering, see Figure 3. [b] Symmetry transforma-
tions used to generate equivalent atoms: (i) x + 1, y, z.
mamides 46[61] (δZ
= 4.56 ppm, δE
= 3.80 ppm) and
= 3.57 ppm) as well as to
2-H
2-H
48[62] (δZ
= 4.34 ppm, δE
2-H
2-H
that of ureido derivatives 47[20] and 49.[63] For the corre-
sponding E conformers, the 2-H resonance should be
The crystal data and refinement parameters of 30 and 40
are summarized in Table 3.
shifted upfield (δE
Ϸ 3.6 ppm) (Figure 4). Accordingly,
2-H
the major, or exclusive, conformer in solution for the urey-
lenedisaccharides 34–43 should exhibit a Z,Z geometry, and
the Z-conformer will also be the preferred arrangement of
models compounds 44 and 45.
Conclusion
A series of sugar isocyanates have been prepared, by
means of useful and safe methods, starting from diversely
substituted amino sugars, which can also be obtained in a
few steps from commercially available sources. These isocya-
nates could be advantageously employed for the construc-
tion of libraries of new glycoconjugates, namely ureidodi-
saccharides, exemplified here by a series of substances com-
bining different sugar skeleta and configurations. The syn-
thetic protocol is simple and products can easily be isolated
and purified. Both spectroscopic and crystallographic
analyses reveal a well-defined conformational trend, includ-
ing the association of such substances at a supramolecular
level in the solid state, which could be relevant in crystal
engineering. These results should therefore be of benefit to
readers interested in the development and application of
glycomimetics.
Experimental Section
Figure 4. Z-conformers for compounds 46–49.
General Methods: All solvents were purchased from commercial
sources and used as received unless otherwise stated. Melting
points were determined with Gallenkamp and Electrothermal ap-
paratus and are uncorrected. Analytical TLC were performed on
precoated Merck 60 GF254 silica gel plates with a fluorescent indi-
Further evidences about the preferential conformation of
these glycoconjugates arise from the solid-state structure of
40 (vide supra), in which the molecular disposition adopted
in the crystal unit is virtually coincidental with a Z-trans,Z- cator, and detection by means of UV light at 254 and 360 nm and
iodine vapours. Optical rotations were measured at 20 2 °C with
a Perkin–Elmer 241 polarimeter. IR spectra were recorded in the
range 4000–600 cm–1 with FT-IR THERMO spectrophotometer.
trans conformation. The urea linkage shows a Z,Z arrange-
ment and one of the sugar fragments (d-gluco) exhibits a
trans relationship between the vicinal 2-H and NH protons.
For the other sugar moiety (d-galacto), an approximate
trans geometry can also be found (Figure 3). Finally, it is
worth pointing out the macromolecular association of the
ureidosugars in the crystalline state (Table 2). Hydrogen
bonds connect the NH groups with two different oxygen
atoms of a vicinal molecule, the urea carbonyl and the an-
omeric acetate.
1
Solid samples were recorded on KBr (Merck) pellets. H- and 13C
NMR spectra were recorded on a Bruker 400 AC/PC instrument
at 400 and 100 MHz, respectively, or with a Bruker AC 200-E in-
strument at 200 and 50.3 MHz, respectively, in different solvent
systems. Assignments were confirmed by homo- and hetero-nuclear
double-resonance, DEPT (distortionless enhancement by polariza-
tion transfer), and variable-temperature experiments. TMS was
used as the internal standard (δ = 0.00 ppm) and all J values are
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J. C. Palacios et al.
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Table 3. Crystal data and structure refinement parameters of 30 and 40.
Compound
30
40
Empirical formula
Formula weight
Temperature [K]
Wavelength [Å]
Crystal system
Space group
Unit cell dimensions
a [Å]
b [Å]
c [Å]
A [°]
B [°]
C17H23NO11
417.36
120(2)
0.71069
monoclinic
P21
C29H40N2O19
720.63
120(2)
0.71073
triclinic
P1
9.310(5)
7.112(5)
16.117(5)
5.2656(6)
9.8828(15)
16.498(2)
81.199(11)
84.504(10)
87.274(11)
844.0(2)
β = 100.563(5)
Γ [°]
V [Å3]
1049.1(10)
Z
2
1
Dcalcd. [Mg/m3]
1.321
0.112
1.418
0.120
M [mm–1]
F(000)
440
380
Crystal size [mm]
Diffractometer
θ Range for data collections (°)
Limiting indices
0.2×0.2×0.1
Nonius-KappaCCD
3.14–25.03
0.6×0.2×0.1
Nonius-KappaCCD
3.01–25.03°
Ϫ6 Յ h Յ 6
Ϫ11 Յ k Յ 11
Ϫ19 Յ l Յ 19
14059
Ϫ10 Յ h Յ 11
Ϫ8 Յ k Յ 8
Ϫ18 Յ l Յ 19
13364
Reflections collected
Refinement method
Parameters / restrains
Goodness-of-fit on F2
Final R indices
[I Ͼ 2σ(I)]
R indices (all data)
Full-matrix least-squares on F2
3673 / 1 / 268
1.029
Full-matrix least-squares on F2
5677 / 3 / 460
1.109
R1 = 0.0812
wR2 = 0.2107
R1 = 0.1124
R1 = 0.0455
wR2 = 0.1042
R1 = 0.0616
wR2 = 0.1107
0.211 and –0.160
wR2 = 0.2393
0.392 and –0.504
Largest diff. peak/ hole [e·Å–3]
given in Hz. Microanalyses were determined with a Leco 932 ana-
lyser at the University of Extremadura (Spain). High-resolution
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-[1-(2,2-diethoxycarbonylvinyl)-
amino]-α-D-galactopyranose (6): To a solution of 5 (1.73 g,
mass spectra (chemical ionization) were recorded with a Micromass 4.95 mmol) in pyridine (17.3 mL) was added acetic anhydride
Autospec spectrometer by the ‘Servicio de Espectrometría de Mas-
as’of the university of Santiago de Compostela (Spain).
(8.6 mL) and the mixture was kept at 0 °C overnight. Then, it was
poured into ice-water. The oily product was extracted with chloro-
form and the organic layer was washed with 1 m HCl, saturated
solution of NaHCO3 and water. Finally, the organic layer was dried
(MgSO4) and concentrated to dryness to give an amorphous pow-
der (2.5 g, 99%) which was crystallized from ethanol/water; m.p.
2-Deoxy-2-[1-(2,2-diethoxycarbonylvinyl)amino]-α-D-galactopyranose
(5): To a stirred solution of 2 (3.0 g, 13.9 mmol) and sodium hydro-
gen carbonate (0.75 g, 6.9 mmol) in water (11 mL) was added di-
ethyl ethoxymethylenemalonate (5.7 mL, 27.8 mmol). A white solid
appeared in a few minutes, which was collected by filtration and
washed with water, cold ethanol and diethyl ether to yield 5 (3.7 g,
77%); recrystallized from ethanol; m.p. 165–166 °C. [α]2D0 = +117.2.
21
21
21
103–104 °C. [α]2D1 = +94.8. [α] = +98.6. [α] = +108.2. [α]
=
578
546
436
+172.6. [α]21 = +257.2 (c = 0.5, CHCl ). IR (KBr): ν = 3275 (NH),
˜
365
3
1757, 1751 (C=O, acetates), 1709 (C=O, H bonded), 1660 (C=O),
1604 (C=C), 1252, 1209 (C–O–C), 1106, 1072, 1013 (C–O) cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.08 (dd, JNH–CH = 13.3 Hz,
JNH,2 = 10.0 Hz, 1 H, NH), 7.94 (d, JNH,CH = 13.4 Hz, 1 H, NH–
CH=C), 6.28 (d, J1,2 = 3.8 Hz, 1 H, 1-H), 5.48 (d, J3,4 = 2.5 Hz,
J4,5 = 0.0 Hz, 1 H, 4-H), 5.22 (dd, J3,4 = 3.2 Hz, J2,3 = 11.0 Hz, 1
H, 3-H), 4.29 (c, J5,6 Ϸ J5,6Ј 10.0 Hz, 1 H, 5-H), 4.20 (c, 2 H, CH2),
4.10 (m, 2 H, 6-H, 6Ј-H), 3.87 (dt, J1,2 = 3.7 Hz, JNH,2 = 10.5 Hz,
1 H, 2-H), 2.24, 2.19, 2.04, 2.00 (s, 4×3 H, OAc), 1.30 (c, 6 H, 2
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.17, 169.74,
168.66, 168.58, 165.69 (C=O),158.93 (CH=C), 92.37 (CH=C),
90.92 (C-1), 68.54 (C-5), 68.33 (C-4), 66.29 (C-3), 60.91 (C-6), 59.97
(CH2), 59.81 (CH2), 56.36 (C-2), 20.63 (OAc), 20.48 (2 OAc), 20.39
(OAc), 14.26 (CH3), 14.09 (CH3) ppm. C22H31NO13 (517.48): calcd:
C 51.06, H 6.04, N 2.71; found C 51.02, H 5.68, N 2.97.
20
20
20
[α] = +123.0. [α] = +141.0. [α] = +258.8 (c = 0.5, pyridine).
578
546
436
IR (KBr): ν = 3500–2300 (OH, NH), 1678 (C=O), 1633 (C=O, H
˜
1
bonded), 1589 (C=C), 1239 (C–O–C), 1081, 1011 (C–O) cm–1. H
NMR (400 MHz, [D6]DMSO): δ = 9.07 (dd, JNH–CH = 14.5 Hz,
JNH,2 = 8.9 Hz, 1 H, NH), 7.99 (d, JNH–CH = 14.4 Hz, 1 H, CH=C),
6.90 (d, JOH,1 = 4.3 Hz, 1 H, 1-OH), 5.11 (t, J1,2 = 3.8 Hz, 1 H, 1-
H), 5.07 (d, JOH,3 = 6.8 Hz, 1 H, 3-OH), 4.71 (d, JOH,4 = 4.5 Hz,
1 H, 4-OH), 4.64 (t, JOH,6 = 5.7 Hz, 1 H, 6-OH), 4.08 (c, JCH2–CH3
= 6.1 Hz, 2 H, CH2), 4.04 (c, JCH2–CH3 = 5.1 Hz, 2 H, CH2), 3.81
(t, J5,6 Ϸ J5,6Ј 6.4 Hz, 1 H, 5-H), 3.75 (t, 1 H, 4-H), 3.58 (m, 3 H,
3-H, 6-H, 2-H), 3.43 (dd, J5,6Ј = 5.2 Hz, J6,6Ј = 10.6 Hz, 1 H, 6Ј-
H), 1.18 (c, JCH2–CH3 = 6.6 Hz, 6 H, 2 CH3) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 168.44 (C=O), 165.41 (C=O), 160.33
(CH=C), 90.98 (C-1), 88.27 (CH=C), 71.04 (C-5), 68.47 (C-4),
68.20 (C-3), 60.68 (C-6), 60.33 (C-2), 59.07 (CH2), 58.89 (CH2), 1,3,4,6-Tetra-O-acetyl-2-amino-2-deoxy-α-D-galactopyranose Hy-
14.66 (CH3), 14.57 (CH3) ppm. C14H25NO10 (367.35): calcd. C
45.77, H 6.86, N 3.81; found C 45.76, H 6.81, N 3.47.
drobromide (7): To a solution of 6 (1.47 g, 3.1 mmol) in chloroform
(11 mL) was added gradually a solution of bromine (0.14 mL) in
664
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Eur. J. Org. Chem. 2006, 657–671

Sugar Isocyanates and Their Application for Ureido-Linked Disaccharides
FULL PAPER
chloroform (8.4 mL) and water (0.05 mL). The mixture was kept at
room temperature; and the product crystallized within 30 minutes.
Then, the flask was kept at 0 °C for 4 hours, diethyl ether was
added (4.8 mL), and the product was collected by filtration (0.9 g,
93.32 (C-1), 71.69 (C-2), 71.48 (C-5), 68.81 (C-3), 65.79 (C-4), 61.22
(C-6), 20.77 (CH3), 20.67 (2×CH3), 20.51 (CH3) ppm. C23H27NO9
(461.46): calcd. C 59.86, H 5.90, N 3.04; found C 59.48, H 5.85, N
2.83.
20
20
70%). M.p. 185–186 °C. [α]2D0 = +96.2. [α]
= +100.8. [α]
= +186.4 (c = 0.5, pyridine). IR (KBr): ν = 3000–
˜
=
578
546
1,3,4,6-Tetra-O-acetyl-2-amino-2-deoxy-β-D-galactopyranose Hy-
20
+114.2. [α]
436
drochloride (10): A solution of 9 (1.84 g, 4.0 mmol) in acetone
(8.6 mL) was heated at reflux. Then, 5 n HCl (0.92 mL) was added
while the temperature was maintained at 40–50 °C. The title com-
pound suddenly crystallized. Then, it was kept at room temperature
for half an hour and subsequently cooled to 0 °C, diethyl ether
2544, 1999 (NH3+), 1766, 1746 (C=O), 1509 (NH3+), 1255, 1242
(C–O–C), 1122, 1049, 1002 (C–O) cm–1. 1H NMR (400 MHz, [D6]-
DMSO): δ = 8.43 (br. s, 3 H, NH), 6.23 (d, J1,2 = 3.5 Hz, 1 H, 1-
H), 5.37 (d, J3,4 = 2.6 Hz, J4,5 = 0.0 Hz, 1 H, 4-H), 5.20 (dd, J3,4
= 3.2 Hz, J2,3 = 11.4 Hz, 1 H, 3-H), 4.38 (t, J5,6 Ϸ J6,6Ј 6.29 Hz, 1
H, 6-H), 4.02 (m, 2 H, 5-H, 6Ј-H), 3.82 (m, 1 H, 2-H), 2.16, 2.12,
2.01, 1.97 (s, 4×3 H, OAc) ppm. 13C NMR (100 MHz, [D6]-
DMSO): δ = 170.09, 170.04, 169.63, 168.97 (C=O, acetates), 88.98
(C-1), 68.21 (C-3), 67.15 (C-5), 66.25 (C-4), 61.13 (C-6), 47.14 (C-
2), 20.99, 20.81, 20.70, 20.59 (OAc) ppm. C14H22BrNO9 (428.23):
calcd. C 39.27, H 5.18, N 3.27; found C 39.10, H 5.29, N 3.58.
(6.2 mL) was added and the product was collected by filtration to
22
yield pure 10 (1.1 g, 73%). M.p. 204–206 °C. [α]2D2 = +4.2. [α]
=
˜
578
+3.4. [α]22 = +5.2. [α]22 = +22.8 (c = 0.5, pyridine). IR (KBr): ν
546
436
= 3100–2545 (NH3+), 2008 (NH3+), 1778, 1751, 1747 (C=O), 1599,
1510 (NH3+), 1250, 1222, 1209 (C–O–C), 1113, 1074, 1065 (C–O)
cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 8.77 (br. s, 3 H, NH),
5.89 (d, J1,2 = 8.7 Hz, 1 H, 1-H), 5.29 (m, 2 H, 3-H, 4-H), 4.29 (t,
J5,6 Ϸ J6,6Ј 6.2 Hz, 1 H, 6-H), 3.37 (m, 3 H, 2-H, 5-H, 6Ј-H), 2.16
(s, 3 H, OAc), 2.12 (s, 3 H, OAc), 2.05 (s, 3 H, OAc), 1.99 (s, 3 H,
OAc) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 170.08 (C=O),
169.51 (C=O), 168.83 (C=O), 92.46 (C-1), 71.23 (C-3), 68.99 (C-
5), 65.95 (C-4), 61.35 (C-6), 49.54 (C-2), 21.03 (CH3), 20.87 (CH3),
20.67 (CH3), 20.51 (CH3) ppm. C14H22ClNO9 (383.78): calcd. C
43.81, H 5.78, N 3.65; found C 44.09, H 6.23, N 3.96.
2-[(E)-Cinnamylidene]amino-2-deoxy-β-D-galactopyranose (8): To a
stirred solution of 2 (1.0 g, 4.7 mmol) and sodium hydrogen car-
bonate (0.5 g, 6.0 mmol) in water (6 mL) was added gradually a
solution of trans-cinnamaldehyde (0.63 mL, 5.0 mmol) in methanol
(5 mL). The title compound crystallized in a few minutes, which
was washed with water, cold ethanol and diethyl ether (0.8 g, 62%)
followed by recrystallization from methanol; m.p. 171–172 °C.
19
19
19
[α]D19 = +55.0. [α] = +58.0. [α] = +70.0. [α] = +122.2 (c = 0.5,
578
546
436
1,3,4,6-Tetra-O-acetyl-2-amino-2-deoxy-α-D-glucopyranose Hydro-
pyridine). IR (KBr): ν = 3500–2800 (OH), 1636 (CH=CH–C=N),
˜
bromide (11): From 1,3,4,6-tetra-O-acetyl-2-deoxy-2-[1-(2,2-di-
ethoxycarbonylvinyl)amino]-α-d-glucopyranose[37] (13.9 g,
26.8 mmol) following the same route as for compound 7 the title
compound 11 was obtained. (7.42 g, 65%), (ref.[39] [α]D = +118.2).
1
1449 (arom.), 1163, 1067 (C–O), 750, 690 (arom.) cm–1. H NMR
(400 MHz, [D6]DMSO): δ = 7.95 (d, J=CH–CH = 8.8 Hz, 1 H,
N=CH–CH), 7.59 (d, J = 8.3 Hz, 2 H, Ar), 7.36 (m, 3 H, Ar),
7.09 (d, JCH=CH = 16.1 Hz, 1 H, CH=CH–Ar), 6.89 (dd, JCH=CH
23
23
M.p. 190–192 °C. [α]2D3 = +117.2. [α] = +121.2. [α] = +136.8.
578
546
= 16.1 Hz, JCH–Ar = 8.8 Hz, 1 H, CH=CH–Ar), 6.49 (d, J1,OH
6.9 Hz, 1 H, 1-OH), 4.63 (t, J6,OH = 5.6 Hz, 1 H, 6-OH), 4.58 (m,
J1,2 = 7.5 Hz, J3,OH = 5.7 Hz, 2 H, 1-H, 3-OH), 4.45 (d, J4,OH
=
23
[α]
436
= +228.0 (c = 0.5, H O). IR (KBr): ν = 3100–2535, 1765
˜
2
(C=O), 1510 (NH3+), 1223 (C–O–C), 1030 (C–O) cm–1. H NMR
1
=
(400 MHz, [D6]DMSO): δ = 8.57 (br. s, 3 H, NH), 6.19 (d, J1,2
=
4.5 Hz, 1 H, 4-OH), 3.66 (t, J3,4 = 3.8 Hz, J4,5 = 0.0 Hz, 1 H, 4-H),
3.58 (m, 2 H, 3-H, 6-H), 3.52 (dd, J6,6Ј = 10.7 Hz, J5,6Ј = 6.3 Hz, 1
H, 6Ј-H), 3.43 (t, J4,5 = 0.0 Hz, J5,6 = J5,6Ј = 6.1 Hz, 1 H, 5-H),
3.02 (dd, J1,2 = 7.7 Hz, J2,3 = 9.6 Hz, 1 H, 2-H) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 163.93 (N=C), 141.03 (2 C, CH=CH),
136.00, 129.25, 129.12, 128.64, 127.39 (C, arom.), 96.32 (C-1), 75.44
(C-5), 74.87 (C-2), 71.87 (C-3), 67.40 (C-4), 60.98 (C-6) ppm.
C15H19NO5 (293.32): calcd. C 61.42, H 6.53, N 4.78; found C
61.09, H 6.54, N 4.87.
3.2 Hz, 1 H, 1-H), 5.25 (d, J3,4 = J4,5 = 10.0 Hz, 1 H, 4-H), 5.00
(dd, J2,3 = J3,4 = 9.7 Hz, 1 H, 3-H), 4.18 (m, 2 H, 5-H, 6-H), 3.98
(d, 1 H, J6,6Ј = 11.6 Hz, 6Ј-H), 3.91 (dd, 1 H, J1,2 = 3.1 Hz, J2,3
=
10.6 Hz, 2-H), 2.24, 2.19, 2.04, 1.98 (s, 4×3 H, OAc) ppm. 13C
NMR (100 MHz, [D6]DMSO): δ = 170.18, 169.43, 168.94 (C=O,
acetates), 88.36 (C-1), 69.20 (C-3), 69.04 (C-5), 67.49 (C-6), 61.20
(C-4), 50.37 (C-2), 21.09, 20.73, 20.54 (OAc) ppm.
1-Deoxy-1-[(2,2-diethoxycarbonyvinyl)]amino-D-glucitol (17): To a
solution of 4 (8.4 g, 46.42 mmol) in methanol (250 mL) was added
diethyl ethoxymethylenemalonate (15.5 mL, 62.5 mmol). The mix-
ture was stirred at room temperature for 24 hours, resulting in the
formation of a solid that was filtered (13.7 g 84 %). M.p. 204–
1,3,4,6-Tetra-O-acetyl-2-[(E)-cinnamylidene]amino-2-deoxy-β-D-gal-
actopyranose (9): To a stirred and cooled suspension (0 °C) of 8
(0.25 g, 0.9 mmol) in pyridine (1.2 mL) was added acetic anhydride
(1.1 mL). The mixture was kept at 0 °C for 12 hours. Then, it was
poured into ice-water and, on stirring and scrapping, the title com-
pound was obtained as a solid that was filtered and washed with
plenty cold water (0.29 g, 71%). M.p. 205–206 °C. [α]2D1 = +41.4.
206 °C. IR (KBr): ν = 3500–3200 (OH), 1651, 1605 (C=C), 1271
˜
1
(C–O–C), 1150, 1013 cm–1 (C–O). H NMR (400 MHz, CDCl3): δ
= 9.19 (dt, JNH,CH2 = 6.6 Hz, JNH,CH= = 13.2 Hz, 1 H, NH), 7.98
(d, JNH,CH= = 14.8 Hz, 1 H, CH=), 4.99 (d, 1 H, J2,OH = 5.6 Hz,
2-OH), 4.50 (d, 1 H, J4,OH = 5.2 Hz, 4-OH), 4.43 (m, 2 H, 3-OH,
5-OH), 4.35 (t, 1 H, J6,OH Ϸ J6Ј,OH 5.6 Hz, 6-OH), 4.09 (2 H, c,
JCH3,CH2 = 7.2 Hz, CH2CH3), 4.05 (2 H, c, JCH3,CH2 = 7.1 Hz,
CH2CH3), 3.64–3.28 (m, 8 H, 1-H, 1Ј-H, 2-H, 3-H, 4-H, 5-H, 6-H,
[α]21 = +101.0. [α]21 = +289.4 (c = 0.5, CHCl ). IR (KBr): ν =
˜
578
546
3
1748 (C=O, acetates), 1643 (CH=CH–C=N), 1449 (arom.), 1244
(C–O–C), 1065 (C–O), 763, 698 (arom.) cm–1. 1H NMR (400 MHz,
CDCl3): δ = 8.06 (d, J=CH–CH = 8.8 Hz, 1 H, N=CH–CH), 7.49 (d,
J = 6.6 Hz, 2 H, Ar), 7.37 (m, 3 H, Ar), 7.04 (d, JCH=CH = 16.0 Hz,
1 H, CH=CH–Ar), 6.86 (dd, JCH=CH = 16.0 Hz, JCH–CH = 8.8 Hz,
1 H, CH=CH–Ar), 5.88 (d, J1,2 = 8.2 Hz, 1 H, 1-H), 5.46 (d, J3,4
6Ј-H), 1.20 (t, JCH3,CH2 = 7.1 Hz, 3 H, CH3), 1.18 (t, JCH3,CH2
=
7.1 Hz, 1 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.07,
165.45 (C=O), 160.40 (C=CH), 87.96 (C=CH), 72.02 (C-2), 71.46
(C-4), 71.27 (C-5), 70.16 (C-3), 63.50 (C-6), 58.88, 58.79 (2 C, CH2),
52.10 (C-1), 14.52, 14.46 (2 C, CH3) ppm.
= 3.1 Hz, J4,5 = 0.0 Hz, 1 H, 4-H), 5.20 (dd, J3,4 = 3.2 Hz, J2,3
10.4 Hz, 1 H, 3-H), 4.19 (m, 3 H, 5-H, 6-H, 6Ј-H), 3.55 (dd, J1,2
=
=
8.4 Hz, J2,3 = 10.3 Hz, 1 H, 2-H), 2.18 (s, 3 H, OAc), 2.08 (s, 3 H,
OAc), 2.06 (s, 3 H, OAc), 1.95 (s, 3 H, OAc) ppm. 13C NMR 2,3,4,5,6-Penta-O-acetyl-1-deoxy-1-[(2,2-diethoxycarbonylvinyl)]ami-
(100 MHz, CDCl3): δ = 170.42 (C=O), 170.06 (C=O), 169.57 no- -glucitol (18): To a cooled solution of 17 (12.7 g, 36.3 mmol)
D
(C=O), 168.63 (C=O), 167.05 (N=C), 143.67 (2 ×C, CH=CH), in pyridine (105 mL) was added gradually acetic anhydride
135.09, 129.70, 128.90 (arom.), 127.41 (2 C, arom.), 127.32 (arom.), (158 mL). The mixture was kept at 0 °C for 2 hours. Then it was
Eur. J. Org. Chem. 2006, 657–671
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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665

J. C. Palacios et al.
FULL PAPER
poured into ice-water and was extracted with chloroform
(3×125 mL). The organic layer was washed with a solution of 1 n
HCl (2×250 mL), a saturated solution of NaHCO3 (2×250 mL),
water (2×250 mL), and dried (anhydrous MgSO4). The solution
was evaporated to dryness and the title compound was obtained as
1015 (C–O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 6.29 (d, J1,2
3.5 Hz, 1 H, 1-H), 5.46 (d, J3,4 = 1.9 Hz, J4,5 = 0.0 Hz, 1 H, 4-H),
5.24 (dd, J3,4 = 3.1 Hz, J2,3 = 11.0 Hz, 1 H, 3-H), 4.30 (t, J5,6
J5,6Ј 6.7 Hz, J4,5 = 0.0 Hz, 1 H, 5-H), 4.09 (m, 3 H, 2-H, 6-H, 6Ј-
H), 2.20, 2.16, 2.08, 2.04 (s, 4 × 3 H, OAc) ppm. 13C NMR
(100 MHz, CDCl3): δ = 170.32, 169.97, 169.89, 168.78 (C=O, ace-
=
Ϸ
an oily residue (20.3 g, 100%). IR (KBr): ν = 1748, (C=O, acetates),
˜
1658 (C=O), 1610 (CH=CH), 1431 (arom.), 1219 (C–O–C), 1048 tate), 125.92 (NCO), 90.41 (C-1), 69.65 (C-4), 68.70 (C-3), 66.53
(C–O), 803, 756 (arom.) cm–1. 1H NMR (400 MHz, CDCl3): δ = (C-5), 60.99 (C-6), 51.90 (C-2), 20.83 (OAc), 20.61 (2 OAc), 20.53
9.19 (dt, JNH,CH2 = 6.9 Hz, JNH,CH= = 13.9 Hz, 1 H, NH), 7.92 (d,
(2 OAc) ppm. C15H19NO10 (373.31): calcd. C 48.26, H 5.13, N 3.75;
JNH,CH= = 13.9 Hz, 1 H, CH=), 5.40 (m, 2 H, 3-H, 4-H), 5.17 (dd, found C 48.11, H 5.19, N 3.93.
J2,3 = 5.1 Hz, 1 H, 2-H), 5.05 (dd, 1 H, 5-H), 4.26–4.13 (m, 4 H,
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-isocyanato-β-D-galactopyranose
(23): From 10 and following the methods A (45%) and B (65%)
6-H, 6Ј-H, 2 CH2CH3), 3.62 (dt, 1 H, 1-H), 3.49 (dt, J1,1Ј = 14.1 Hz,
J1,2 = 7.4 Hz, 1 H, 1Ј-H), 2.14, 2.13, 2.11, 2.10, 2.05, 2.04 (s, 4×3
the title compound 23 was obtained. Recrystallized from diethyl
H, OAc), 1.32 (t, JCH3,CH2 = 7.4 Hz, 3 H, CH3), 1.27 (t, JCH3,CH2
=
19
ether/petroleum ether. M.p. 149–150 °C. [α]1D9 = +27.2. [α]
=
˜
578
7.4 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 169.98,
169.68, 169.48, 169.43, 169.32, 168.40, 165.32 (C=O), 159.74
(C=CH), 90.90 (C=CH), 70.05 (C-2), 68.45 (C-3), 68.31 (C-4),
68.17 (C-5), 60.89 (C-6), 59.46, 59.24 (2 C, CH2), 48.81 (C-1),
20.16, 20.00 (CH3), 14.01, 13.90 (2 C, CH3CH2) ppm.
+29.0. [α]19 = +32.6. [α]19 = +57.2 (c = 0.5, CDCl ). IR (KBr): ν
546
436
3
= 2260 (N=C=O), 1756, 1741 (C=O), 1245, 1216 (C–O–C), 1048
(C–O) cm–1 1H NMR (400 MHz, CDCl3): δ = 5.59 (d, J1,2
8.7 Hz, 1 H, 1-H), 5.40 (d, J3,4 = 3.1 Hz, J4,5 = 0.0 Hz, 1 H, 4-H),
4.95 (dd, J3,4 = 3.4 Hz, J2,3 = 10.7 Hz, 1 H, 3-H), 4.15 (dd, J5,6
.
=
=
7.2 Hz, J6,6Ј = 11.0 Hz, 6-H), 4.12 (d, J5,6Ј = 6.7 Hz, 1 H, 6Ј-H),
4.05 (m, J5,6Ј = 6.6 Hz, J4,5 = 0.0 Hz, 1 H, 5-H), 3.77 (t, J1,2 Ϸ J2,3
9.4 Hz, 1 H, 2-H), 2.20, 2.16, 2.08, 2.04 (s, 3 H, OAc) ppm. 13C
NMR (100 MHz, CDCl3): δ = 170.30, 169.88, 169.69, 168.65
(C=O, acetates), 126.99 (NCO), 92.76 (C-1), 71.85 (C-3, C-5), 65.96
(C-4), 60.86 (C-6), 53.77 (C-2), 20.73, 20.61, 20.52, 20.43 (OAc)
ppm. C15H19NO10 (373.31): calcd. C 48.26, H 5.13, N 3.75; found
C 48.48, H 4.93, N 3.86.
2,3,4,5,6-Penta-O-acetyl-1-amino-1-deoxy-D-glucitol Hydrobromide
(19): To a solution of 18 (21.9 g, 36.3 mmol) in chloroform
(300 mL) was added gradually a solution of bromine (1.57 mL) in
chloroform (98 mL) and water (0.6 mL) until the solution showed
a persistent orange color. The mixture was kept at 0 °C for 4 hours.
Then, the product was filtered off and washed with diethyl ether
20
to give 19 (12.2 g, 73%). M.p. 205–207 °C. [α]2D0 = –2.6. [α]
=
578
20
20
20
–1.8. [α] = –1.6. [α] = –1.0. [α] = –1.4 (c = 0.5, H2O). IR
546
436
365
(KBr): ν = 3200–2900 (NH +), 1755 (C=O), 1501 (NH3+), 1215
˜
3
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-isocyanato-α-
(24): From 11 and following the methods A (65%) and B (64%)
the title isocyanate 24 was obtained. M.p. 113–114 °C. [α]2D0
D-glucopyranose
(C–O–C), 1073, 1048, 1027 cm–1 (C–O). 1H NMR (400 MHz,
CDCl3): δ = 8.07 (br. s, 3 H, NH3+), 5.29 (m, 2 H, 3-H, 4-H), 5.18
(m, 1 H, 2-H), 4.99 (dt, J5,6 = 2.9 Hz, J5,6Ј = 6.2 Hz, 1 H, 5-H),
4.22 (dd, J5,6Ј = 2.9 Hz, J6,6Ј = 12.4 Hz, 1 H, 6-H), 4.07 (dd, J5,6Ј
= 6.4 Hz, J6,6Ј = 12.4 Hz, 1 H, 6Ј-H), 3.41 (br. s, 1 H, 1-H), 3.02
(br. s, 1 H, 1Ј-H), 2.10, 2.05, 2.03, 1.99, 1.98 (s, 4×3 H, OAc) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.23, 170.18, 169.88, 169.74,
169.68 (C=O), 68.95 (C-2), 68.62 (C-3), 68.35 (C-4), 68.30 (C-5),
61.51 (C-6), 39.08 (C-1), 21.25, 20.89, 20.78, 20.67, 20.62 (CH3,
acetates) ppm. C16H26BrNO10 (472.28): calcd. C 40.69, H 5.55, N
2.87; found C 40.33, H 5.33, N 2.51.
=
20
20
20
+143.6. [α] = +145.0. [α] = +164.0. [α] = +254.8 (c = 0.5,
578
546
436
CHCl ). IR (KBr): ν = 2259 (N=C=O, isocyanate), 1753 (C=O),
˜
3
1221 (C–O–C), 1154 cm–1 (C–O). H NMR (400 MHz, CDCl3): δ
1
= 6.23 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 5.37 (t, J2,3 Ϸ J3,4 9.9 Hz, 1 H,
3-H), 5.05 (t, J3,4 Ϸ J4,5 9.7 Hz, 1 H, 4-H), 4.27 (dd, J5,6 = 3.7 Hz,
J6,6Ј = 12.3 Hz, 1 H, 6-H), 4.08 (dddd, J5,6 = 3.8 Hz, J5,6Ј = 2.3 Hz,
J4,5 = 10.2, 1 H, 5-H), 4.02 (dd, J5,6Ј = 2.3 Hz, J6,6Ј = 12.3 Hz, 1
H, 6Ј-H), 3.78 (dd, J1,2 = 3.6 Hz, J2,3 = 10.5 Hz, 1 H, 2-H), 2.20,
2.09, 2.05, 2.02 (s, 3 H, OAc) ppm. 13C NMR (100 MHz, CDCl3):
δ = 170.4, 170.1, 169.4, 168.5 (C=O, acetates), 125.8 (NCO), 89.8
(C-1), 71.8 (C-3), 69.8 (C-5), 67.4 (C-4), 61.3 (C-6), 55.5 (C-2), 20.7,
20.6, 20.5 (4 OAc) ppm. C15H19NO10 (373.31): calcd. C 48.26, H
5.13, N 3.75; found C 48.10, H 5.20, N 3.79.
General Procedures for the Synthesis of Protected Sugar Isocya-
nates. Method A: To a cooled solution of pyridine (0.32 mL) in
anhydrous dichloromethane (10 mL) was added the corresponding
O-protected amino sugar (1.0 mmol) and the mixture was stirred
vigorously at 0 °C for 30 min. Then, it was added dropwise a solu-
tion of phosgene in toluene (1.93 m, 1.1 mL, 2.0 mmol). The mix-
ture was stirred at 0 °C for 2 additional hours. The reaction mixture
was washed with 0.5 n HCl (2 × 5 mL), a saturated solution of
NaCl (5 mL), dried with anhydrous MgSO4, and concentrated to
dryness. The oily residue was crystallized from diethyl ether/petro-
leum ether. Method B: To a heterogeneus mixture of the corre-
sponding O-protected amino sugar (4.6 mmol) in dichloromethane
(50 mL) and saturated solution of NaHCO3 (30 mL) was added
triphosgene (1.35 g, 4.6 mmol) The mixture was stirred vigorously
at 0 °C for 30 min. The organic layer was separated, washed with
a saturated solution of NaCl, dried (Na2SO4), and concentrated to
dryness. The white powder obtained was further crystallized from
diethyl ether/petroleum ether.
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-isocyanato-β-
D-glucopyranose
(25): From 12 and following the methods A (51%) and B (96%)
21
compound 25 was obtained. M.p. 75–76 °C. [α]2D1 = +35.2. [α]
=
578
21
21
21
+37.0. [α] = +41.4. [α] = +74.6. [α] = +121.2 (c 0.5, CDCl3).
546
436
365
[ref.[42] m.p. 71–72 °C. [α]D = 35.9. [α]578 = 37.5 (c = 1.0,
HCONMe )]. IR (KBr): ν = 2263 (N=C=O), 1742 (C=O), 1236
˜
2
(C–O–C), 1047 (C–O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 5.59
(d, J1,2 = 8.6 Hz, 1 H, 1-H), 5.15 (t, J2,3 Ϸ J3,4 9.8 Hz, 1 H, 3-H),
5.00 (t, J3,4 Ϸ J4,5 9.5 Hz, 1 H, 4-H), 4.28 (dd, J5,6 = 4.2 Hz, J6,6Ј
= 12.5 Hz, 1 H, 6-H), 4.06 (dd, J6,6Ј = 12.5 Hz, 1 H, 6Ј-H), 3.84
(dddd, J5,6Ј = 2.1 Hz, J5,6 = 4.1 Hz, J4,5 = 10.0 Hz, 1 H, 5-H), 3.77
(t, J1,2 Ϸ J2,3 9.4 Hz, 1 H, 2-H), 2.17, 2.08, 2.06, 2.01 (s, 3 H, OAc)
ppm. 13C NMR (100 MHz, CDCl3): δ = 170.4, 169.7, 169.5, 168.6
(C=O, acetates), 126.6 (NCO), 92.4 (C-1), 73.2 (C-3), 72.8 (C-5),
67.5 (C-4), 61.3 (C-6), 56.8 (C-2), 20.6 (OAc), 20.6 (OAc), 20.4 (2
OCH3) ppm. C15H19NO10 (373.31): calcd. C 48.26, H 5.13, N 3.75;
found C 48.42, H 5.10, N 3.99.
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-isocyanato-α-
D-galactopyranose
(22): From 7 and following the method B the isocyanate 22 was
20
obtained (70%). M.p. 106–107 °C. [α]2D0 = +115. [α]
= +116.2.
578
[α]20 = +128.0. [α]20 = +195.4 (c = 0.5, CHCl ). IR (KBr): ν =
3,4,6-Tri-O-acetyl-2-deoxy-2-isocyanato-β-
D-glucopyranosyl Azide
˜
540
436
3
2275 (N=C=O), 1745 (C=O), 1250, 1209 (C–O–C, ester), 1042, (27): To a solution of 14 (1.0 g, 3.0 mmol) in dichloromethane
666
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 657–671

Sugar Isocyanates and Their Application for Ureido-Linked Disaccharides
FULL PAPER
(33 mL) was added triphosgene (0.89 g, 3.0 mmol) and the mixture
was stirred vigorously at 0 °C for 30 min. Then, it was concentrated
to dryness, and the white residue was recrystallized from diethyl
ether/petroleum ether to give 27 (0.39 g, 37%). M.p. 109–110 °C.
+43.6. [α]19 = +69.8 (c = 0.5, CHCl ). IR (KBr): ν = 2267, 2241
˜
365 3
(N=C=O), 1745 (C=O), 1223 (C–O–C, ester), 1078, 1045 (C–O)
cm–1. 1H NMR (400 MHz, CDCl3): δ = 5.47 (dd, J3,4 = 3.5 Hz,
J4,5 = 7.0 Hz, 1 H, 4-H), 5.36 (dd, J2,3 = 7.6 Hz, J3,4 = 3.5 Hz, 1
20
20
20
[α]2D0 = +3.6. [α] = +4.2. [α] = +5.2. [α] = +11.8 (c = 0.5,
H, 3-H), 5.04 (m, 2 H, 2-H, 5-H), 4.25 (dd, J5,6 = 3.2 Hz, J6,6Ј =
578
546
436
CDCl ). IR (KBr): ν = 2240 (N=C=O), 2119 (N=N=N), 1750 12.5 Hz, 1 H, 6-H), 4.14 (dd, J5,6Ј = 4.8 Hz, J6,6Ј = 12.5 Hz, 1 H,
˜
3
(C=O), 1240, 1222 (C–O–C), 1113, 1067, 1039 cm–1 (C–O). 1H 6Ј-H), 3.59 (dc, J1,1Ј = 4.7 Hz, J1,2 = 4.4 Hz, 2 H, 1-H), 2.14, 2.12,
NMR (400 MHz, CDCl3): δ = 5.10 (t, J2,3 Ϸ J3,4 9.8 Hz, 1 H, 3- 2.09, 2.08 (s, 4×3 H, OAc) ppm. 13C NMR (100 MHz, CDCl3): δ
H), 5.00 (t, J4,5 Ϸ J3,4 9.7, 1 H, 4-H), 4.70 (d, J1,2 = 8.9 Hz, 1 H,
1-H), 4.30 (dd, J5,6 = 4.8 Hz, J6,6Ј = 12.5 Hz, 1 H, 6-H), 4.15 (dd,
= 170.45, 169.90, 169.84, 169.66 (C=O acetates), 124.11 (NCO),
69.91 (C-4), 68.32 (C-3), 68.26 (C-2, C-5), 61.27 (C-6), 42.87 (C-1),
20.67 (OAc), 20.61 (2 OAc), 20.37 (OAc) ppm. C17H23NO11
(417.36): calcd. C 48.92, H 5.55, N 3.36; found C 48.95, H 5.73, N
J5,6Ј = 2.2 Hz, J6,6Ј = 12.5 Hz, 1 H, 6Ј-H), 3.81 (dddd, J5,6Ј
=
2.3 Hz, J5,6 = 4.7 Hz, J4,5 = 10.0, 1 H, 5-H), 3.57 (dd, J1,2 = 9.1 Hz,
J2,3 = 9.9 Hz, 1 H, 2-H), 2.10 (s, 6 H, OAc), 2.04 (s, 3 H, OAc) 3.00.
ppm. 13C NMR (100 MHz, CDCl3): δ = 170.5, 169.8, 169.4 (C=O,
2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl Isocyanate (31): From 21
acetates), 126.6 (NCO), 89.2 (C-1), 74.1 (C-5), 73.3 (C-3), 67.6 (C-
4), 61.5 (C-6), 57.7 (C-2), 20.6 (OAc), 20.5 (2 OAc) ppm.
C13H16N4O8 (356.29): calcd. C 43.82, H 4.53, N 15.73; found C
44.12, H 4.80, N 15.70.
and following the methods A (51%) and B (86%) the title com-
pound 31 was obtained. M.p. 117–119 °C (ref.[23] m.p. 118–120 °C).
Tetrahydro-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoso)[2,1-
d]-1,3-oxazol-2-one (32): To a mixture of 13 (3.4 g, 9.0 mmol) in
chloroform (40 mL) was added a solution of sodium carbonate
(3.24 g, 30.6 mmol) in water (20 mL) and, finally, a 1.93 m solution
of phosgene in toluene (7.0 mL). The mixture was stirred vigor-
ously for 12 h. Then, it was filtered and the organic layer was sepa-
rated, washed with water, dried (anhydrous CaCl2) and the solvents
evaporated. The resulting residue was crystallized from diethyl
ether-petroleum ether to give the title product (2.53 g, 88%). M.p.
1,3,4,6,7-Penta-O-acetyl-2-deoxy-2-isocyanato-β-D-glycero-L-gluco-
heptopyranose (28): From 15 and following the methods A (55%)
and B (52 %) the title compound 28 was obtained. M.p. 112–
22
22
22
113 °C. [α]2D2 = +115.4. [α]
= +116.0. [α]
= +133.0. [α]
=
578
546
436
+211.8 (c = 0.5, CHCl ). IR (KBr): ν = 2265 (N=C=O), 1755
˜
3
(C=O), 1223 (C–O–C), 1142, 1032 (C–O) cm–1 1H NMR
.
(400 MHz, CDCl3): δ = 6.25 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 5.37 (t,
J2,3 Ϸ J3,4 9.9 Hz, 1 H, 3-H), 5.24 (t, J6,7 Ϸ J6,7Ј 6.1 Hz, 1 H, 6-
H), 5.01 (t, J4,5 Ϸ J3,4 9.9 Hz, 1 H, 4-H), 4.22 (dd, J6,7 = 5.2 Hz,
J7,7Ј = 11.6 Hz, 1 H, 7-H), 4.14 (m, J6,7Ј = 7.5 Hz, J7,7Ј = 11.4 Hz,
2 H, 7Ј-H, 5-H), 3.81 (dd, J1,2 = 3.7 Hz, J2,3 = 10.4 Hz, 1 H, 2-H),
2.27 (s, 3 H, OCH3), 2.11 (s, 6 H, OCH3), 2.03 (s, 3 H, OCH3),
2.03 (s, 3 H, OCH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.3
(CH3-CO), 170.1 (2 CH3–CO), 169.5 (CH3–CO), 168.3 (CH3–CO),
126.9 (NCO), 89.8 (C-1), 72.0 (C-3), 70.0 (C-5), 66.7 (C-4), 66.5
(C-6), 61.9 (C-7), 55.5 (C-2), 20.7 (CH3–CO), 20.6 (3 CH3–CO),
20.4 (2 CH3–CO) ppm. C18H23NO12 (445.37): calcd. C 48.54, H
5.21, N 3.14; found C 48.31, H 5.30, N 3.20.
20
20
20
175–177 °C. [α]2D0 = +23.4. [α] = +25.4. [α] = +28.8. [α]
=
578
546
436
20
+47.4. [α] = +71.6 (c = 0.5, CHCl3). [ref.[13,50,51] m.p. 171.0–172.5
365
or 170 or 174–175 °C, [α]D = +23 5 (c = 2.0, CHCl3) or 33.0 (c =
2, CHCl ) or 29 (c = 1, CHCl )]. IR (KBr): ν = 3249 (NH), 1744
˜
3
3
(C=O, ester), 1261, 1224, 1190 (C–O–C, ester), 1079, 1046, 1015
1
(C–O) cm–1. H NMR (400 MHz, CDCl3): δ = 6.31 (s, 1 H, NH),
5.98 (d, J1,2 = 7.0 Hz, 1 H, 1-H), 5.04 (dd, J3,4 = 5.4 Hz, J4,5
=
9.1 Hz, 1 H, 4-H), 4.97 (dd, J2,3 = 4.1 Hz, J3,4 = 5.3 Hz, 1 H, 3-
H), 4.32 (dd, J5,6 = 5.3 Hz, J6,6Ј = 12.3 Hz, 1 H, 6-H), 4.21 (dd,
J5,6Ј = 2.6 Hz J6,6Ј = 12.5 Hz, 1 H, 6Ј-H), 4.12 (ddd, J5,6Ј = 2.7 Hz,
J5,6 = 5.2 Hz, J4,5 = 8.4 Hz, 1 H, 5-H), 3.93 (dd, J1,2 = 6.9 Hz, J2,3
= 3.9 Hz, 1 H, 2-H), 2.13, 2.10, 2.09 (s, 3 H, OAc each one) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.57, 170.42, 169.45 (C=O,
acetates), 156.32 (C=O), 96.39 (C-1), 73.53 (C-3), 68.39 (C-5), 66.24
(C-4), 62.20 (C-6), 54.28 (C-2), 20.69 (OAc) ppm.
1,3,4,6,7-Penta-O-acetyl-2-deoxy-2-isocyanato-α-D-glycero-L-gluco-
heptopyranose (29): From 16 and following the methods A (63%)
and B (82 %) the title compound 29 was obtained. M.p. 140–
19
19
19
141 °C. [α]1D9 = 0.0. [α] = –3.6. [α] = –8.8. [α] = –36.6 (c =
578
546
436
3-Acetyltetrahydro-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyr-
0.5, CHCl ). IR (KBr): ν = 2261 (N=C=O), 1755 (C=O), 1242 (C–
˜
3
O–C), 1109, 1072, 961 (C–O) cm–1. H NMR (400 MHz, CDCl3):
1
anoso)[2,1-d]-1,3-oxazol-2-one (33): To a solution of 32 (0.35 g,
1.1 mmol) in pyridine (4 mL) was added acetic anhydride (4 mL)
and the mixture was kept at room temperature overnight. Then it
was poured into ice-water and extracted with chloroform
(3×25 mL). The combined extracts were washed with 1 m HCl, sat-
urated solution of aqueous NaHCO3 and water; dried (MgSO4),
and the solvents evaporated. A colourless oil that further solidified
could be obtained (0.43 g, 100%). M.p. 108–109 °C. [α]2D0 = –31.4.
δ = 5.54 (d, 1 H, J1,2 = 8.4 Hz, 1-H), 5.28 (dt, 1 H, J6,7 Ϸ J6,7Ј
5.4 Hz, J5,6 = 2.3 Hz, 6-H), 5.16 (t, J3,4 Ϸ J2,3 9.9 Hz, 1 H, 3-H),
5.01 (t, J4,5 Ϸ J3,4 9.7, 1 H, 4-H), 4.27 (dd, J6,7 = 5.3 Hz, J7,7Ј
=
11.6 Hz, 1 H, 7-H), 4.11(dd, J6,7Ј = 7.7 Hz, J7,7Ј = 11.2 Hz, 1 H,
7Ј-H), 3.90 (d, J4,5 = 10.1 Hz, J5,6 = 2.2 Hz, 1 H, 5-H), 3.80 (t, J1,2
Ϸ J2,3 9.4 Hz, 1 H, 2-H), 2.19 (s, 3 H, OAc), 2.09 (s, 6 H, OAc),
2.05, 2.01 (s, 3 H, OAc) ppm. 13C NMR (100 MHz, CDCl3): δ =
170.4, 170.0, 169.75, 168.4 (5 C=O, acetates), 126.6 (NCO), 92.8
(C-1), 73.4 (C-3), 73.0 (C-5), 66.7 (C-4), 66.3 (C-6), 61.8 (C-7), 56.7
(C-2), 20.6 (3 OAc), 20.4 (2 OAc) ppm. C18H23NO12 (445.37):
calcd. C 48.54, H 5.21, N 3.14; found C 48.54, H 5.21, N 3.34.
20
20
20
20
[α]
578
= –32.8. [α]
= –37.6. [α]
= –75.2. [α]
= –134.8 (c =
546
436
365
0.5, CHCl3). HRMS-CI (C15H19NO10 [M + H]+): calcd. for
374.10872; found: 374.10958.
General Procedures for the Synthesis of Protected Ureas: To a solu-
tion of the corresponding isocyanate (1.0 mmol) in pyridine (6 mL)
was added the O-protected amino sugar (1.0 mmol) and the mix-
ture was kept at room temperature for 24 h. Then, it was poured
into ice-water and the resulting white solid was collected by fil-
tration, washed with cold water and recrystallized from ethanol/
water.
2,3,4,5,6-Tetra-O-acetyl-1-deoxy-1-isocyanato-D-glucitol (30): To a
solution of triphosgene (0.17 g, 0.56 mmol) in dichloromethane
(6 mL) was added a saturated solution of NaHCO3 (4 mL) and
then 19 (0.30 g, 0.56 mmol). The mixture was stirred vigorously at
0 °C for 30 min. The organic layer was separated, washed with a
saturated solution of NaCl, and dried (anhydrous Na2SO4). It was
concentrated to dryness and a white powder was obtained (0.21 g,
80%). Recrystallized from diethyl ether/petroleum ether it had m.p.
N,NЈ-Bis(1,3,4,6-tetra-O-acetyl-2-deoxy-α-D-galactopyranos-2-yl)-
urea (34): From 7 and 22, the title compound was obtained (64%).
19
19
19
20
20
95–97 °C. [α]1D9 = +20.8. [α]
= +22.8. [α]
= +24.8. [α]
=
M.p. 146–148 °C. [α]2D0 = +107.0. [α] = +112.0. [α] = +126.4.
578
546
436
578 546
Eur. J. Org. Chem. 2006, 657–671
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
667

J. C. Palacios et al.
FULL PAPER
[α]20 = +212.0. [α]20 = +212.0 (c = 0.5, CHCl ). IR (KBr): ν =
2 H, 5-H), 2.10 (s, 3 H, OAc), 2.09 (s, 3 H, OAc), 2.07 (s, 2×3 H,
˜
436
365
3
3417, 3375 (NH), 1750 (C=O), 1697 (C=O, urea),1552 (NH), 1256, OAc) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.22, 170.66,
1225 (C–O–C, ester), 1165, 1137, 1067 (C–O) cm–1 1H NMR 169.66, 169.45 (8 C=O, acetates), 156.47 (C=O, urea), 93.35 (C-1),
.
(400 MHz, CDCl3): δ = 6.16 (d, J1,2 = 3.6 Hz, 2 H, 1-H), 5.40 (d, 72.60 (C-3), 72.54 (C-5), 68.14 (C-4), 61.88 (C-6), 54.01 (C-2), 20.73
J3,4 = 2.3 Hz, J4,5 = 0.0 Hz, 2 H, 4-H), 5.14 (dd, J3,4 = 3.2 Hz, J2,3 (3 OAc), 20.65 (2 OAc), 20.52 (3 OAc) ppm. C29H40N2O19 (720.63):
= 11.4 Hz, 2 H, 3-H), 4.85 (d, JNH,2 = 9.6 Hz, 2 H, NH), 4.52 (ddd, calcd. C 48.33, H 5.59, N 3.89; found C 48.11, H 5.73, N 4.08.
J1,2 = 3.7 Hz, JNH,2 Ϸ J2,3 9.7 Hz, 2 H, 2-H), 4.23 (t, J5,6Ј Ϸ J5,6
N-(1,3,4,6-Tetra-O-acetyl-2-deoxy-α-D-glucopyranos-2-yl)-NЈ-
6.8 Hz, J4,5 = 0.0 Hz, 2 H, 5-H), 4.14 (m, J5,6 = 6.8 Hz, J6,6Ј
=
(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-2-yl)urea (38):
From 12 and 24 urea 38 was obtained (86%). M.p. 213-214 °C.
11.3 Hz, 4 H, 6-H, 6Ј-H), 2.18 (s, 3 H, OAc), 2.15 (s, 3 H, OAc),
2.04 (s, 3 H, OAc), 2.03 (s, 2 × 3 H, OAc) ppm. 13C NMR
(100 MHz, CDCl3): δ = 171.54, 170.45, 170.21, 168.84 (2 C, C=O,
acetates), 156.01 (C=O, urea), 91.78 (2 C, C-1), 68.60 (1 C, C-4),
67.94 (2 C, C-3), 66.81 (2 C, C-5), 61.32 (2 C, C-6), 47.79 (2 C, C-
2), 20.77 (2 C, OAc), 20.71 (2 C, OAc), 20.59 (4C, OAc) ppm.
C29H40N2O19 (720.63): calcd. C 48.33, H 5.59, N 3.89; found C
47.79, H 5.63, N 4.06. HRMS-FAB (C29H40N2O19Na [M + Na]+):
calcd. for 743.2120; found 743.2130.
21
21
21
21
[α]2D1 = +60.4. [α] = +62.6. [α] = +71.2. [α] = +120.2. [α]
578
546
436
365
= +183.8 (c = 0.5, CHCl ). IR (KBr): ν = 3410 (NH), 1750 (C=O),
˜
3
1674 (C=O, urea), 1561 (NH), 1235 (C–O–C, ester), 1042 (C–O)
1
cm–1. H NMR (400 MHz, CDCl3): (α-glucose and β-glucose resi-
dues have been labelled A and B, respectively): δ = 6.18 (d, J1,2
=
3.6 Hz, 1 H, 1-HA), 5.70 (d, J1,2 = 8.6 Hz, 1 H, 1-HB), 5.29 (d,
JNH,2 = 9.0 Hz, 1 H, NHB), 5.19 (d, JNH,2 = 2.4 Hz, 1 H, NHA),
5.19 (t, J2,3 Ϸ J3,4 10.0 Hz, 2 H, 3-HA and 3-HB), 5.09 (t, J3,4
J4,5 9.4 Hz, 2 H, 4-HA and 4-HB), 4.33 (dt, J1,2 = 3.5 Hz, J2,3
Ϸ
=
N,NЈ-Bis(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-galactopyranos-2-yl)-
urea (35): From 10 and 23, compound 35 was obtained (62%). M.p.
7.7 Hz, 1 H, 2-HA), 4.26 (dd, J6,6Ј = 12.6 Hz, J5,6 = 5.0 Hz, 2 H,
6-HA and 6-HB), 4.13 (dd, J6,6Ј = 12.3 Hz, J5,6Ј = 1.8 Hz, 1 H, 6Ј-
HA), 4.11 (t, 1 H, 2-HB), 4.07 (dd, J6,6Ј = 12.4 Hz, J5,6Ј = 2.2 Hz,
1 H, 6Ј-HB), 4.02 (dd, J5,6Ј = 2.0 Hz, J5,6 = 5.9 Hz, 1 H, 5-HB),
3.87 (ddd, J5,6Ј = 2.2 Hz, J5,6 = 4.9 Hz, J4,5 = 9.3 Hz, 1 H, 5-HA),
2.14 (s, 3 H, OCH3), 2.09 (s, 2×3 H, OAc), 2.05 (s, 4×3 H, OAc),
22
22
22
208–209 °C. [α]2D2 = +10.2. [α] = +12.0. [α] = +13.0. [α]
=
578
546
436
+24.2. [α]22 = +40.0 (c = 0.5, CHCl ). IR (KBr): ν = 3414 (NH),
˜
365
3
1752 (C=O), 1698 (C=O, urea), 1547 (NH), 1241 (C–O–C, ester),
1
1146, 1089, 1075, 1046 (C–O) cm–1. H NMR (400 MHz, CDCl3):
δ = 5.76 (d, J1,2 = 8.7 Hz, 2 H, 1-H), 5.36 (d, J3,4 = 3.3 Hz, J4,5
=
0.0 Hz, 2 H, 4-H), 5.16 (dd, J3,4 = 2.6 Hz, J2,3 = 10.9 Hz, 2 H, 3- 2.04 (s, 3 H, OAc) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.20
H), 4.89 (d, JNH,2 = 9.1 Hz, 2 H, NH), 4.12 (m, 8 H, 2-H, 5-H, 6-
H, 6Ј-H), 2.18, 2.13, 2.05, 2.03 (s, 2×3 H, OAc) ppm. 13C NMR
(100 MHz, CDCl3): δ = 170.78, 170.42, 170.24, 169.60 (2 C×2,
(2×C=O), 170.60 (2×C=O), 169.33 (2×C=O), 169.15 (C=O, ace-
tates), 159.17 (C=O, urea), 92.99 (C-1B), 90.77 (C-1A), 72.45 (C-3B,
C-5B), 70.27 (C-3A), 69.68 (C-5A), 68.05 (C-4B), 67.63 (C-4A), 61.74
C=O, acetates), 156.35 (C=O, urea), 93.24 (2 C, C-1), 71.69 (1 C, (C-6B), 61.69 (C-6A), 53.83 (C-2B), 51.76 (C-2A), 20.52 (3 OAc),
C-3), 70.54 (2 C, C-5), 66.56 (2 C, C-4), 61.36 (2 C, C-6), 51.19 (2
C, C-2), 20.86 (2 C, OAc), 20.67 (2 C, OAc) ppm. C29H40N2O19
(720.63): calcd. C 48.33, H 5.59, N 3.89; found C 48.42, H 5.66, N
3.98.
20.38 (5 OAc) ppm. C29H40N2O19 (720.63): calcd. C 48.33, H 5.59,
N 3 . 8 9 ; fo u n d C 4 8 . 7 7 , H 5 . 5 1 , N 4 . 1 4 . H R M S - FAB
(C29H40N2O19Na [M + Na]+): calcd. for 743.2120; found 743.2134.
N-(1,3,4,6-Tetra-O-acetyl-2-deoxy-2-α-D-glucopyranos-2-yl)-NЈ-
N,NЈ-Bis(1,3,4,6-tetra-O-acetyl-2-deoxy-α-D-glucopyranos-2-yl)urea
(36): From 11 and 24, compound 36 was obtained (60%). M.p.
(3,4,6-tri-O-acetyl-1-azido-1,2-dideoxy-β-D-glucopyranos-2-yl)urea
(39): To a solution of 25 (0.20 g, 0.53 mmol) in freshly distilled
chloroform (6.0 mL) 14 (0.20 g, 0.53 mmol) was added. The mix-
ture was kept at room temperature for 24 h. Then, it was concen-
trated to dryness to give the title compound (0.33 g, 88%) that was
21
21
21
199–201 °C. [α]2D1 = +115.8. [α] = +121.6. [α] = +138.4. [α]
578
546
436
21
= +233.0. [α]
= +353.2 (c = 0.5, CHCl ). IR (KBr): ν = 3408
˜
3
365
(NH), 1749 (C=O), 1668 (C=O, urea), 1559 (NH), 1227 (C–O–C,
1
ester), 1125, 1040 (C–O) cm–1. H NMR (400 MHz, CDCl3): δ =
recrystallized from ethanol/water. M.p. 172–174 °C. IR (KBr): ν =
˜
6.11 (d, J1,2 = 3.7 Hz, 2 H, 1-H), 5.19 (t, J3,4 Ϸ J2,3 9.7 Hz, 2 H,
3-H), 5.13 (t, J3,4 Ϸ J4,5 10.0 Hz, 2 H, 4-H), 4.69 (d, J2,NH = 9.3 Hz,
2 H, NH), 4.30 (dt, JNH,2 Ϸ J2,3 9.9 Hz, J1,2 = 3.6 Hz, 2 H, 2-H),
3435, 3364 (NH), 2117 (N=N=N), 1747 (C=O), 1671 (C=O), 1556
(NH), 1232 (C–O–C), 1124, 1037 (C–O) cm–1. 1H NMR (400 MHz,
CDCl3) (the glucosyl azide and glucose residues have been labelled
A and B, respectively): δ = 6.18 (d, J1,2 = 3.6 Hz, 1 H, 1-HB), 5.70
4.24 (dd, J6,6Ј = 12.5 Hz, J5,6 = 4.1 Hz, 2 H, 6-H), 4.06 (dd, J6,6Ј
=
12.5 Hz, J5,6Ј = 2.2 Hz, 2 H, 6Ј-H), 3.97 (ddd, J5,6Ј = 2.4 Hz, J5,6 (d, 1 H, J1,2 = 8.6 Hz, 1-HA), 5.21 (t, 2 H, 3-HA and 3-HB), 5.08
= 3.7 Hz, J4,5 = 9.8 Hz, 2 H, 5-H), 2.18, 2.09 (s, 3 H, OAc), 2.04
(t, 2 H, 4-HA and 4-HB), 4.92 (d, JNH,2 = 9.1 Hz, 1 H, NHB), 4.81
(d, JNH,2 = 8.9 Hz, 1 H, NHA), 4.62 (t, J1,2 = 9.2 Hz, 1 H, 1-HA),
(s, 2×3 H, OAc) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.82,
170.73, 169.00, 168.63 (2 C=O, acetates), 155.70 (C=O, urea), 90.83 4.34 (dt, J2,3 Ϸ JNH,2 9.6 Hz, J1,2 = 3.8 Hz, 1 H, 2-HB), 4.25 (m,
(C-1), 70.72 (C-3), 69.60 (C-5), 67.45 (C-4), 61.55 (C-6), 51.70 (C- J5,6 = 5.6 Hz, J6,6Ј = 12.4 Hz, 2 H, 6-HA and 6-HB), 4.16 (dd, J6,6Ј
2), 20.60 (5 OAc), 20.41 (3 OAc) ppm. C29H40N2O19 (720.63):
calcd. C 48.33, H 5.59, N 3.89; found C 48.32, H 5.65, N 3.79.
= 12.4 Hz, J5,6Ј = 1.9 Hz, 1 H, 6Ј-HA), 4.07 (dd, J6,6Ј = 12.5 Hz,
J5,6Ј = 2.0 Hz, 1 H, 6Ј-HB), 4.01 (m, J5,6 = 5.7 Hz, J4,5 = 9.1 Hz, 1
H, 5-HB), 3.77 (m, 2 H, 5-HA, 2-HA), 2.14, 2.11 (s, 3 H, OAc), 2.09
(s, 2×3 H, OAc), 2.08, 2.05, 2.03 (s, 3 H, OAc) ppm. 13C NMR
(100 MHz, CDCl3): δ = 171.91 (C=O), 171.27 (2×C=O), 170.75,
169.27, 169.12, 168.72 (C=O), 156.01 (C=O, urea), 91.06 (C-1A),
89.20 (C-1B), 73.84 (C-3A), 72.57 (C-5A), 70.76 (C-3B), 69.80 (C-
5B), 68.06 (C-4A), 67.56 (C-4B), 61.86 (C-6A), 61.62 (C-6B), 55.03
(C-2A), 51.98 (C-2B), 20.70 (5 OAc), 20.55 (3 OAc) ppm.
C27H37N5O17 (703.61): calcd. C 46.09, H 5.30, N 9.95; found C
46.07, H 5.26, N 9.66.
N,NЈ-Bis(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-2-yl)urea
(37): From 12 and 25, compound 37 was obtained (81%). M.p.
21
21
21
231–232 °C. [α]2D1 = +16.8. [α] = +19.0. [α] = +20.8. [α]
=
578
546
436
21
+39.8. [α]
= +66.8 (c = 0.5, CHCl3). [ref.[42] m.p. 230–232 °C,
365
[α]D = +44.7, [α]578 = +45.4 (c = 0.95, HCONMe )]. IR (KBr): ν
˜
2
= 3343 (NH), 1757 (C=O, ester), 1653 (C=O, urea), 1550 (NH),
1252 (C–O–C, ester), 1084 cm–1(C–O). 1H NMR (400 MHz,
CDCl3): δ = 5.75 (d, J1,2 = 8.7 Hz, 2 H, 1-H), 5.47 (d, JNH,2
9.4 Hz, 2 H, NH), 5.21 (t, J2,3 Ϸ J3,4 9.9 Hz, 2 H, 3-H), 5.12 (t,
J3,4 Ϸ J4,5 9.6 Hz, 2 H, 4-H), 4.27 (dd, J6,6Ј = 12.4 Hz, J5,6 = 5.2 Hz, N-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-galactopyranos-2-yl)-NЈ-
=
2 H, 6-H), 4.16 (m, J1,2 Ϸ JNH,2 Ϸ J2,3 9.4 Hz, 2 H, 2-H), 4.12 (dd,
2 H, 6Ј-H), 3.86 (ddd, J5,6Ј = 2.0 Hz, J5,6 = 5.0 Hz, J4,5 = 9.7 Hz,
(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-2-yl)urea (40): To
a solution of 23 (0.20 g, 0.53 mmol) in freshly distilled chloroform
668
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 657–671

Sugar Isocyanates and Their Application for Ureido-Linked Disaccharides
(6.0 mL) was added the 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β- J2,NH = 9.0 Hz, 1 H, NH), 4.30 (dd, J5,6 = 4.5 Hz, J6,6Ј = 11.7 Hz,
FULL PAPER
d-glucopyranose (0.18 g, 0.53 mmol), easily generated by washing
a solution of the hydrochloride in chloroform with a saturated solu-
tion of NaHCO3, then dried, and the solvents evaporated to dry-
ness. The mixture was kept at room temperature for 24 hours.
Then, it was concentrated to dryness to give a solid (0.27 g, 72%)
1 H, 6-HA), 4.27 (dd, J6,7 = 4.5 Hz, J7,7Ј = 12.6 Hz, 1 H, 7-HB),
4.14 (dd, J6,7Ј = 7.6 Hz, J7,7Ј = 11.8 Hz, 1 H, 7Ј-HB), 4.12 (dd, J5,6
= 2.0 Hz, J6,6Ј = 12.7 Hz, 1 H, 6Ј-HA), 4.00 (m, J2,NH Ϸ J1,2 Ϸ J2,3
10.1, 2 H, 2-HA and 2-HB), 3.86 (dd, J4,5 = 9.8 Hz, J5,6 = 1.9 Hz,
1 H, 5-HB), 3.83 (dc, J4,5 = 9.6 Hz, J5,6 = 2.2 Hz, J5,6 = 4.4 Hz, 1
which was recrystallized from ethanol-water. M.p. 214–215 °C. H, 5-HA), 2.14, 2.11, 2.09, 2.08, 2.06, 2.05, 2.04, 2.02, 2.01 (s, 9 x 3
[α]1D9 = +15.0. [α] = +15.4. [α] = +18.2. [α] = +32.2. [α]
H, OAc) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.53, 171.45,
= +53.8 (c = 0.5, CHCl ). IR (KBr): ν = 3408, 3326 (NH), 1750 170.63, 170.57, 170.35, 169.54, 169.45 (C=O, acetates), 169.27
19
19
19
19
578
546
436
365
˜
3
(C=O), 1679 (C=O), 1553 (NH), 1226 (C–O–C), 1084, 1040 (C–
(2×C=O, acetates), 155.97 (C=O, urea), 93.09 (C-1A), 92.89 (C-
1B), 73.12 (C-3B), 72.97 (C-5B), 72.63 (C-3A and C-5A), 67.96 (C-
4A), 66.96 (C-4B), 66.50 (C-6B), 62.43 (C-7B), 61.65 (C-6A), 54.32
(C-2A, C-2B), 20.79 (3 OAc), 20.61 (6 OAc) ppm. HRMS-FAB
1
O) cm–1. H NMR (400 MHz, CDCl3): (the glucose and galactose
residues have been labelled A and B, respectively): δ = 5.76 (d, J1,2
= 8.7 Hz, 2 H, 1-HA and 1-HB), 5.36 (d, J3,4 = 3.3 Hz, J4,5 = 0.0 Hz,
1 H, 4-HB), 5.18 (m, 4 H, 3-HA and 3-HB, NHA and NHB), 5.10 (C32H44N2O21Na [M + Na]+): calcd. for 815.2329; found 815.2335.
(t, J3,4 = 9.7 Hz, 1 H, 4-HA), 4.28 (dd, J5,6 = 4.8 Hz, J6,6Ј = 12.5 Hz,
N,NЈ-Bis(2,3,4,5,6-tetra-O-acetyl-1-deoxy-D-glucitol-1-yl)urea (43):
1 H, 6-HA), 4.04 (m, J1,2 Ϸ J2,3 Ϸ JNH,2 9.4 Hz, 1 H, 2-HA), 3.88
(ddd, J5,6Ј = 2.2 Hz, J5,6 = 4.7 Hz, J4,5 = 9.8 Hz, 1 H, 5-HA), 4.17
(m, 5 H, 6-HB, 6Ј-HA and 6Ј-HB, 5-HB, 2-HB), 2.16 (s, 3 H, OAc),
2.14 (s, 3 H, OAc), 2.11 (s, 3 H, OAc), 2.09 (s, 3 H, OAc), 2.08 (s,
3 H, OAc), 2.03 (s, 3 H, OAc), 2.04 (s, 2×3 H, OAc) ppm. 13C
NMR (100 MHz, CDCl3): δ = 171.27 (C=O), 170.72 (C=O), 170.63
(2×C=O), 170.33 (2 ×C=O), 169.51 (C=O), 169.44 (C=O), 156.34
(C=O, urea), 93.47 (C-1A), 93.05 (C-1B), 72.66 (C-3A), 72.52 (C-
5A), 71.56 (C-3B), 70.38 (C-5B), 68.13 (C-4A), 66.51 (C-4B), 61.75
(C-6A), 61.40 (C-6B), 54.16 (C-2A), 50.92 (C-2B), 20.83 (2 OAc),
20.73 (3 OAc), 20.56 (3 OAc) ppm. C29H40N2O19 (720.63): calcd.
C 48.33, H 5.59, N 3.89; found C 48.40, H 5.67, N 3.62.
From 19 and 30 the title compound 43 was obtained (40%). M.p.
20
20
20
133–135 °C. [α]2D0 = +32.8. [α] = +33.2. [α] = +36.2. [α]
=
578
546
436
+70.6 (c = 0.5, CHCl ). IR (KBr): ν = 3403, 3348 (NH, crystalli-
˜
3
zation H2O), 1744 (C=O), 1649 (C=O), 1567 (NH), 1221 (C–O–
1
C), 1050 (C–O) cm–1. H NMR (400 MHz, CDCl3): δ = 5.49 (dd,
J3,4 = 4.4 Hz, J4,5 = 6.7 Hz, 2 H, 4-H), 5.36 (dd, J2,3 = 5.4 Hz, J3,4
= 4.6 Hz, 2 H, 3-H), 5.06 (m, 4 H, 2-H, 5-H), 4.90 (t, 2 H, NH),
4.27 (dd, J5,6 = 3.2 Hz, J6,6Ј = 12.4 Hz, 2 H, 6-H), 4.13 (dd, J5,6Ј
5.6 Hz, J6,6Ј = 12.4 Hz, 1 H, 6Ј-H), 3.47 (dt, J1,1Ј = 13.7 Hz, J1,2
=
=
6.3 Hz, 2 H, 1-H), 3.25 (dt, J1,1Ј = 12.6 Hz, J1,2 = 6.8 Hz, 2 H, 1-
H), 2.13, 2.10, 2.09, 2.08, 2.05 (s, 10×3 H, OAc) ppm. 13C NMR
(100 MHz, CDCl3): δ = 170.63, 170.54, 170.30, 169.86 (C=O, ace-
tates), 157.22 (C=O, urea), 71.03 (C-2), 69.17 (C-4), 68.72 (C-5, C-
3), 61.50 (C-6), 40.33 (C-1), 20.75, 20.67, 20.52 (CH3, acetates)
ppm. C33H48N2O21·2H2O (844.77): calcd. C 46.92, H 6.20, N 3.32;
found C 47.36, H 6.43, N 2.74. HRMS-FAB (C33H48N2O21Na [M
+ Na]+): calcd. for 831.2640; found 831.2662.
N-(1,3,4,6,7-Penta-O-acetyl-2-deoxy-β-D-glycero-L-gluco-heptopyr-
anos-2-yl)–NЈ-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-2-
yl)urea (41): From 15 and 25, compound 41 was obtained. (76%).
21
21
M.p. 147–149 °C. [α]2D1 = –30.0. [α]
= –31.6. [α]
= –35.6.
˜
578
546
α]21 = –58.4. [α]21 = –82.0 (c = 0.5, CHCl ). IR (KBr): ν = 3383
436
365
3
(NH), 1751 (C=O), 1690 (C=O), 1543 (NH), 1217 (C–O–C), 1045
(C–O) cm–1. 1H NMR (400 MHz, CDCl3): (the glucose and hep-
tose residues have been labelled A and B, respectively): δ = 6.17 (d,
J1,2 = 3.7 Hz, 1 H, 1-HB), 5.62 (d, J1,2 = 8.7 Hz, 1 H, 1-HA), 5.18
(dt, J5,6 = 2.0 Hz, J6,7 Ϸ J6,7Ј 4.7 Hz, 1 H, 6-HB), 5.13 (m, 2 H, 3-
HA and 3-HB, 4-HA), 5.05 (t, J3,4 Ϸ J4,5 9.9 Hz, 1 H, 4-HB), 4.80
(d, 1 H, J2,NH = 9.0 Hz, NH), 4.67 (d, 1 H, J2,NH = 9.3 Hz, NH),
1,3,4,6-tetra-O-acetyl-2-deoxy-2-ureido-α-D-glucopyranose (44): To
a solution of 11 (4.28 g, 10.0 mmol) in water (40 mL) was added
silver cyanate (1.90 g, 12.7 mmol). The mixture was stirred at 40–
50 °C and then the solid was collected by filtration, and washed
with water, ethanol and diethyl ether to give 44 (0.97 g, 25%). M.p.
19
19
19
204–206 °C. [α]1D9 = +118.8. [α] = +123.7. [α] = +139.8. [α]
578
546
436
= +230.4. [α] = +345.8 (c = 1.0, H2O). [ref.[59] m.p. 202 °C. [α]D
19
365
4.24 (m, 3 H, 6-HA, 7-HB, 2-HA), 4.13 (m, J7,7Ј = 11.6 Hz, J7,6
=
= 115 (c = 1, H O)]. IR (KBr): ν = 3492, 3367 (NH), 1758 (C=O,
˜
2
4.5 Hz, J6,6Ј = 12.8 Hz, J5,6 = 2.5 Hz, 2 H, 6Ј-HA, 7Ј-HB), 4.05 (m,
J5,6 = 2.4 Hz, J4,5 = 9.5 Hz, 5-HB, 2-HB), 3.78 (ddd, J4,5 = 9.8 Hz,
J5,6 = 2.3 Hz, J5,6Ј = 4.6 Hz 1 H, 5-HA), 2.14, 2.11, 2.09, 2.07, 2.04,
2.02, 2.01 (s, 9 x 3 H, OAc) ppm. 13C NMR (100 MHz, CDCl3): δ
= 171.60, 171.28, 170.68, 170.59, 170.36, 169.79, 169.21, 169.06,
168.24 (C=O, acetates), 155.84 (C=O, urea), 92.86 (C-1A), 90.80
(C-1B), 72.92 (C-3A), 72.67 (C-5A), 70.80 (C-3B), 69.99 (C-5B),
67.77 (C-4A), 66.62 (C-4B, C-6B), 62.23 (C-7B), 61.69 (C-6A), 54.01
(C-2A ), 52.11 (C-2B ), 20.61 (9 OAc) ppm. HRMS-ESI
(C32H44N2O21Na [M + Na]+): calcd. for 815.2329; found 815.2348.
ester), 1660 (C=O, urea), 1555 (NH), 1220 (C–O–C, ester), 1008
(C–O) cm–1 1H NMR (400 MHz, CDCl3): δ = 6.19 (d, J1,2
. =
3.6 Hz, 1 H, 1-H), 6.00 (d, JNH,2 = 9.2 Hz, 1 H, NH), 5.26 (t, J2,3
Ϸ J3,4 10.0 Hz, 1 H, 3-H), 5.20 (t, J3,4 Ϸ J4,5 9.6 Hz, 1 H, 4-H),
5.13 (2 H,s, NH2), 4.24 (dd, J1,2 = 3.6 Hz, 1 H, 2-H), 4.24 (dd, J5,6
= 3.4 Hz, J6,6Ј = 10.6 Hz, 1 H, 6-H), 4.05 (dd, J5,6 = 1.6 Hz, J6,6Ј
= 12.4 Hz, 1 H, 6Ј-H), 4.03 (m, J5,6Ј = 1.8 Hz, J4,5 = 10.0 Hz, 1 H,
5-H), 2.19, 2.10, 2.06, 2.05 (s, 4 × 3 H, OAc) ppm. 13C NMR
(100 MHz, CDCl3): δ = 171.32, 170.72, 169.17 (C=O, acetates),
158.52 (C=N), 91.01 (C-1), 70.78 (C-3), 69.72 (C-5), 67.57 (C-4),
61.56 (C-6), 51.71 (C-2), 20.95, 20.74, 20.65, 20.50 (CH3, acetates)
ppm.
N-(1,3,4,6,7-Penta-O-acetyl-2-deoxy-α-D-glycero-L-gluco-heptopyr-
anos-2-yl)-NЈ-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-2-
yl)urea (42): From 16 and 25, compound 42 was obtained (68%).
21
21
M.p. 229–230 °C. [α]2D1 = +14.6. [α]
= +15.4. [α]
= +18.2.
˜
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-ureido-β-D-glucopyranose (45): To
578
546
[α]21 = +31.0. [α]21 = +50.6 (c = 0.5, CHCl ). IR (KBr): ν = 3408,
a solution of 12 (3.84 g, 10.0 mmol) in water (40 mL) was added
436
365
3
3336 (NH), 1748 (C=O), 1665 (C=O, urea), 1545 (NH), 1234 (C– silver cyanate (1.90 g, 12.7 mmol). The mixture was stirred at 40–
1
O–C, ester), 1071, 1038 cm–1(C–O). H NMR (400 MHz, CDCl3):
50 °C. and then the solid was collected by filtration, and washed
(the glucose and heptose residues have been labelled A and B,
with water, ethanol and diethyl ether to give 45 (1.35 g, 35%). M.p.
22
22
22
respectively): δ = 5.75 (d, J1,2 = 8.8 Hz, 1 H, 1-HA), 5.72 (d, J1,2
=
204–206 °C. [α]2D2 = +32.0. [α] = +33.2. [α] = +38.0. [α]
=
578
546
436
9.0 Hz, 1 H, 1-HB), 5.24 (dt, J6,7 Ϸ J6,7Ј 5.1 Hz, J5,6 = 2.6 Hz, 1 H, +65.8 (c = 0.5, DMF). [ref.[60] m.p. 190–191 °C. [α]D = 24.5 (c =
6-HB), 5.18 (t, J3,4 Ϸ J2,3 9.6 Hz, 1 H, 3-HA), 5.16 (t, J3,4 Ϸ J2,3
9.5 Hz, 1 H, 3-HB), 5.13 (t, J4,5 Ϸ J3,4 9.6, 1 H, 4-HA), 5.11 (t, J4,5
Ϸ J3,4 9.5, 1 H, 4-HB), 5.03 (d, J2,NH = 9.1 Hz, 1 H, NH), 5.01 (d,
1.305 g/100 mL, CHCl )]. IR (KBr): ν = 3486, 3356 (NH), 1755
˜
3
(C=O, ester), 1666 (C=O, urea), 1564 (NH), 1262, 1216 (C–O–C,
1
ester), 1073, 1041 (C–O) cm–1. H NMR (400 MHz, [D6]DMSO):
Eur. J. Org. Chem. 2006, 657–671
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
669

J. C. Palacios et al.
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δ = 5.94 (d, JNH,2 = 9.6 Hz, 1 H, NH), 5.75 (d, J1,2 = 8.0 Hz, 1 H,
1-H), 5.63 (2 H,s, NH2), 5.22 (t, J2,3 Ϸ J3,4 10.0 Hz, 1 H, 3-H),
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=
8.8 Hz, 1 H, 1-H), 5.19 (t, J2,3 Ϸ J3,4 9.7 Hz, 1 H, 3-H), 5.14 (t,
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4.65 (2 H,s, NH2), 4.28 (dd, J5,6 = 4.5 Hz, J6,6Ј = 12.5 Hz, 1 H, 6-
H), 4.12 (dd, J5,6 = 2.0 Hz, J6,6Ј = 12.4 Hz, 1 H, 6-H), 4.02 (1 H,
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= 9.4 Hz, J5,6 = 4.4 Hz 1 H, 5-H), 2.15, 2.10, 2.08, 2.04 (s, 3 H,
OAc) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 171.02, 170.59,
170.26, 169.96 (C=O, acetates), 158.89 (C=O, urea), 93.32 (C-1),
73.55 (C-3), 72.28 (C-5), 69.25 (C-4), 62.55 (C-6), 53.88 (C-2),
21.59, 21.47, 21.41 (CH3, acetates) ppm.
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Sugar Isocyanates and Their Application for Ureido-Linked Disaccharides
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