Nitrosation of sugar oximes: Preparation of 2-glycosyl-1-hydroxydiazene-2- oxides

Article abstract of DOI:10.1002/chem.200500325

Oximes of glucose, xylose, lactose, fructose, and mannose have been prepared. Nitrosation of the oximes of glucose, xylose, and lactose with NaNO₂/HCl afforded 2-(β-glycopyranosyl)-1-hydroxydiazene-2- oxides, which were isolated as salts 13, 22

Full text of DOI:10.1002/chem.200500325

FULL PAPER
DOI: 10.1002/chem.200500325
Nitrosation of Sugar Oximes: Preparation of 2-Glycosyl-1-hydroxydiazene-2-
oxides
Jçrg Brand, Thomas Huhn, Ulrich Groth, and Johannes C. Jochims*[a]
Abstract: Oximes of glucose, xylose,
lactose, fructose, and mannose have
been prepared. Nitrosation of the
oximes of glucose, xylose, and lactose
with NaNO2/HCl afforded 2-(b-glyco-
pyranosyl)-1-hydroxydiazene-2-oxides,
which were isolated as salts 13, 22, and
28. Nitrosation of fructose oxime 29
furnished fructose, whereas nitrosation
of mannose oxime 30 with NaNO2/HCl
afforded the 1-hydroxy-2-(b-d-manno-
pyranosyl)diazene-2-oxide 32, from
which the p-anisidinium salt 31 and the
sodium salt 33 were prepared. Howev-
er, nitrosation of 30 with isopentyl ni-
trite in aqueous solutions of CsOH or
KOH resulted in the formation of the
2-(a-d-mannofuranosyl)-1-hydroxydia-
zene-2-oxide salts 34 and 35, respec-
tively. Methylation of the ammonium
2-(b-d-glucopyranosyl)-1-hydroxydia-
zene-2-oxide 13 yielded the 1-methoxy
compound, which was benzoylated to
afford the tetra-O-benzoate 14a, the
structure of which was confirmed by X-
ray diffraction analysis. From the glu-
cose O-methyloximes 15 and 16 the N-
methoxy-N-nitroso-2,3,4,6-tetra-O-ace-
tyl-b-d-glucopyranosylamine 18 was
prepared. The structure of this com-
pound was confirmed by X-ray diffrac-
tion analysis. Treatment of acetobro-
moglucose with cupferron furnished
the 1-(2,3,4,6-tetra-O-acetyl-b-d-gluco-
pyranosyloxy)-2-phenyldiazene-2-oxide
20.
Keywords: carbohydrates · glycosyl
oximes · nitrosation · NO donors ·
X-ray diffraction
Introduction
lem is to develop NO donors capable of providing the re-
quired quantities of NO to the specific tissue of need with-
out disturbing other NO-sensitive portions of the anatomy.
Thus, Wang and co-workers have prepared glycosylated hy-
droxydiazene-2-oxides such as the glucosyl derivative 6 and
more recently the N-acetylneuraminic acid derivative 7 (to
target influenza viruses) in the expectation that such glyco-
sylated compounds should easily be transported into cells
because of the presence of sugar transporters in the cell
membranes.[10,31,32] Before that, Vasella et al. had synthesized
the glycosides 8 and 9 by oxidation of diisopropylideneman-
nose oxime or tetra-O-benzylglucosylamine, respectively.[33]
The structure of compound 8 was confirmed by X-ray analy-
sis.
In this article we describe the preparations and two X-ray
diffraction analyses of N2-glycosylated diazene-1-olate-2-
oxides: to the best of our knowledge, and with the exception
of compounds 8 and 9, a hitherto unknown class of di-
azeniumdiolates. Building on the work by Wang et al.,[10,31,32]
we also prepared the new cupferron derivative 20
(Scheme 1).
Substituted diazene-1-olate-2-oxides, such as cupferron (1),
are known to release nitric oxide under physiological condi-
tions.[1–3] The endogenously formed nitric oxide displays a
broad variety of bioregulatory activities, including vasodila-
tion, cardiovascular effects, inhibition of platelet aggrega-
tion, and inflammatory and antileukaemic activities, togeth-
er with influences on cognitive processes, on uterine relaxa-
tion, on impotency, and on the immune system.[1–13] In 1998
Furchgott, Ignarro, and Murad were honored with the
Nobel prize for their discoveries of the multiple bioactivities
of NO. A few diazene-1-olate-2-oxides are known as natural
products, for instance (S)-alanosine (2),[14–21] (S)-homoalano-
sine (3),[22] (S)-dopastin (4),[23,24] and (S)-fragin (5).[25,26]
During recent years, numerous diazene-1-olate-2-oxides
(also referred to as diazeniumdiolates[2]) have been prepared
and tested for medicinal applications.[11,27–30] The main prob-
[a] Dr. J. Brand, Dr. T. Huhn, Prof. Dr. U. Groth, Prof. Dr. J. C. Jochims
Fachbereich Chemie der Universität Konstanz, Fach M 733
Universitätsstrasse 10, 78457 Konstanz (Germany)
Fax : (+49)7531-884-155
E-mail: johannes.jochims@uni-konstanz.de
Chem. Eur. J. 2006, 12, 499 –509
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499

1
Results and Discussion
perature over months without decomposition. The H NMR
spectrum of a solution of 13 in D2O remained unchanged
after the sample had been boiled for three minutes. Howev-
er, attempts to acetylate compound 13 with acetic anhydride
in pyridine resulted in penta-O-acetyl-d-glucopyranose.[49–51]
The small crystals of 13 were not appropriate for single-
crystal X-ray diffraction analysis. Therefore we prepared
some derivatives to verify the proposed structure of 13.
Methylation of 13 with dimethyl sulfate followed by ben-
zoylation furnished a crystalline mixture of the 1-methoxy-
diazene-2-oxide 14a and the N-methoxy-N-nitrosohydroxyl-
amine 14b. Recrystallization afforded needles of pure 14a
suitable for X-ray diffraction analysis. Compound 14a crys-
tallizes from ethanol in the orthorhombic space group
P212121 (a=9.371(3), b=16.733(3), c=21.421(4) Š). The
final R (for F2 ꢀ2s(F2)) was 0.0601 and wR=0.1841 (all re-
flections). A stereoscopic view of compound 14a is shown in
Figure 1, and selected bond lengths and angles are given in
Table 1.
Treatment of aldoses and ketoses with hydroxylamine af-
fords open-chain oximes. An exception is glucose, from
which the E- and Z-open-chain oximes 10 and 11 and the N-
b-d-glucopyranosylhydroxylamine 12 have been prepared
(Scheme 1).[34–38] Recently, the synthesis of a cyclic N-b-d-xy-
lofuranosylhydroxylamine has been reported.[39] We pre-
pared the crystalline compound 12 (yield 82%) by stirring
glucose with hydroxylamine in dry methanol at 20–258C.
Under similar conditions we obtained high yields of crystal-
line open-chain oximes from d-xylose, d-lactose, d-fructose,
and d-mannose.
Nitrosations of N-monosubstituted hydroxylamines to
produce 2-substituted diazene-1-olate-2-oxides have been
known for more than 100 years.[40–42] Treatment of the hy-
droxylamine 12 with NaNO2 in dilute hydrochloric acid af-
forded—after neutralization with ammonia—a solid consist-
ing, according to the 1H and 13C NMR spectra (Table 2,
below),
of
a
mixture
of
ammonium
2-(b-d-
To support the structure of compound 14b, glucose was
treated with O-methylhydroxylamine to yield a mixture of
the open-chain (E)- and (Z)-glucose-O-methyloximes 15
and 16.[52–54] Nitrosation resulted in the formation of the
cyclic N-nitroso-O-methylhydroxylamine 17 as a yellow
syrup, and this was acetylated to furnish the crystalline tet-
raacetate 18 (Scheme 1). The constitution of this compound
was also confirmed by X-ray diffraction analysis.[55] Com-
pound 18 crystallizes from THF/pentane in the orthorhom-
bic space group P212121 (a=5.723(1), b=17.650(3), c=
19.666(3) Š). The final R was 0.0479 (for F2 ꢀ2s(F2)) and
wR=0.1311 (for all reflections). A stereoscopic plot of com-
pound 18 is shown in Figure 1 and selected bond lengths
and angles are given in Table 1.
glucopyranosyl)diazene-1-olate-2-oxide (13, 75%), a- and b-
d-glucopyranose (6 and 15%), trace amounts of (E)- and
(Z)-d-glucose oximes 10 and 11, and traces of other sugars,
which were not identified. Crystallization from methanol/
water containing a small amount of NH3 yielded pure com-
pound 13 (yield 65%). The coupling constants—JH1,H2
=
9.0 Hz and JH3,H4 =JH4,H5 =9.4 Hz—are indicative of the b-
pyranosyl structure. The UV absorption—lmax =254 nm (e=
9816mÀ1 cmÀ1)—is characteristic of diazene-1-olate-2-
oxides.[10,33,43–48]
The salt 13 proved to be quite stable: unlike other 2-sub-
stituted diazene-1-olates-2-oxides, which are known to elimi-
nate NO or N2O, compound 13 can be stored at room tem-
500
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Chem. Eur. J. 2006, 12, 499 –509

Nitrosation of Sugar Oximes
FULL PAPER
Scheme 1. Reactions of glucose oximes with NO+ and preparation of the cupferron derivative 20. Structural studies by X-ray crystallography are report-
ed for compounds 14a and 18. a) HCl/H2O+NaNO2. b) NH3/H2O. c) Me2SO4/NaHCO3/H2O. d) BzCl/pyridine. e) Ac2O/pyridine.
After the successful nitrosa-
tion of hydroxylamine 12 we
were interested in how open-
chain sugar oximes would react
with NO+. Xylose has been re-
ported to react with hydroxyl-
amine to form an equilibrium
mixture of the E- and Z-open-
chain oximes and the N-hy-
droxy-b-d-xylopyranosylamine
(ratio about 80:18:3).[57,58] From
d-xylose we obtained a similar
noncrystalline mixture of the
E- and Z-oximes (21) and the
N-hydroxy-b-d-pyranosylamine
1
(Scheme 2). The H NMR spec-
trum of a solution of mixture 21
in D2O did not show any
change over many days. Treat-
ment of an aqueous solution of
this mixture with NaNO2/HCl
Figure 1. Molecular structure of 14a and 18 in the crystal (displacement ellipsoids 50%; C atoms with arbitrary
radii; H atoms omitted for clarity).
Methylation of compound 13 and subsequent acetylation
afforded a mixture of the isomers 18 and 19, which were
separated by crystallization and by column chromatography.
The crystalline cupferron derivative 20 (Scheme 1) was
obtained in moderate yield (ꢁ40%) by treatment of a-ace-
tobromoglucose with cupferron. In water, compound 20 hy-
drolyzed within a few days to mixtures of a- and b-2,3,4,6-
tetra-O-acetyl-d-glucopyranose[55] and azoxybenzene.[56]
and then NH3 yielded the ammonium salt 22 (77%) con-
taminated with a- and b-xylopyranose (ꢁ8% each) togeth-
er with small amounts of other sugars (not identified). Crys-
tallization from H2O/MeOH afforded the pure salt 22, the
constitution of which was characterized by elemental analy-
sis and by NMR and UV spectra. Compound 22 is less
stable than the glucose derivative 13. At 238C the crystals
turned brown in the course of a few weeks, whereas in HCl
Chem. Eur. J. 2006, 12, 499 –509
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501

J. C. Jochims et al.
Table 1. Selected bond lengths [Š] and angles [8] of compounds 14a and 18.
Bond length Bond angle
C1-N2-O2
the open-chain E- and Z-
oximes 26 and the cyclic N-hy-
droxy-b-d-lactopyranosylamine
Torsional angle
C1-N2-N1-O1 179.3(4)
À
C1 C2
14a
1.523(8)
1.406(7)
1.469(7)
1.269(6)
1.264(6)
1.363(6)
1.438(8)
119.1(5)
115.4(5)
125.5(5)
108.0(5)
108.9(5)
À
C1 O3
C1-N2-N1
O2-N2-N1
N2-N1-O1
N1-O1-C35
C2-C1-N2-O2
C2-C1-N2-N1
O3-C1-N2-O2
O3-C1-N2-N1
N2-N1-O1-C35
O2-N2-N1-O1
À50.7(7) 27 (ratio 10 min after dissolu-
À
C1 N2
129.3(5)
67.8(6)
tion in D2O ꢁ0.3:1.0:0.01;
À
N2 N1
Scheme 2). At 238C, the con-
À
N2 O2
À112.2(5)
centration of the hydroxyl-
amine 27 increased slowly over
26 days. The final equilibrium
of the E- and Z-oximes 26 and
the hydroxylamine 27 reached a
ratio of about 5.3:1.0:2.3. Nitro-
À
N1 O1
À176.6(5)
À
O1 C35
À0.7(8)
À
18
C1 C2
1.529(4)
1.412(4)
1.442(4)
1.356(4)
1.385(3)
1.219(4)
1.438(4)
C1-N2-O2
C1-N2-N1
O2-N2-N1
N2-N1-O1
N2-O2-C15
115.0(2)
115.9(3)
119.4(3)
113.8(3)
109.5(2)
C1-N2-N1-O1
C2-C1-N2-O2
C2-C1-N2-N1
O3-C1-N2-O2
O3-C1-N2-N1
O2-N2-N1-O1
N1-N2-O2-C15
C1-N2-O2-C15
À157.9(3)
À
C1 O3
À48.1(3)
À
C1 N2
97.9(3)
72.7(3)
À
N2 N1
À
N2 O2
À141.4(3) sation of the initial mixtures of
À
N1 O1
À13.5(5)
compounds 26 and 27 with
NaNO2/HCl afforded (after
neutralization with NH3 or al-
À
O2 C15
97.2(3)
À118.1(3)
ternatively
KHCO3,
with
CsOH,
NaHCO3,
pyridine,
BuNH2, 4-MeO-C6H4NH2, or
À
Ph2CH NH2) the correspond-
ing diazene-1-olate-2-oxides, of
which the benzhydrylammoni-
um salt 28 (yield 72%) proved
to be the easiest to crystallize
and to purify.
The observed slow cyclization
of the open-chain oximes 26 to
hydroxylamine 27 poses the
question of the mechanism of
the nitrosation. Pursuing the ni-
trosation of the mixture of (E)-
and (Z)-26, containing only
traces of hydroxylamine 27, by
1
using H NMR showed that the
formation of product 28 occurs
much more rapidly (within sec-
onds or at most within a few
minutes) than the cyclizations
of the open-chain oximes 26
(requiring days). Reactions be-
tween oximes and NO+ are
well documented,[61–65] and reac-
tion mechanisms have been
studied.[66–72] In view of mecha-
+
À
Scheme 2. Reactions of xylose, lactose, and fructose oximes with NO . a) HCl/H2O+NaNO2. b) Ph2CH NH2.
c) Ac2O/pyridine.
(1m) compound 22 decomposed into xylose within minutes.
An explanation for the different stabilities of compounds 13
and 22 was offered by one of the referees: Paulsen has
pointed out that removing one OR group (the 6-CH2OH
group of 13 to give 22) increases the reactivity of the glyco-
syl donor, the reactivity correlating with the oxycarbenium
cation stability.[59] The crystalline acetylated N-methoxy-N-
nitrosoxylopyranosylamine 25 was prepared from com-
pounds 23[52–54] in the manner described for compound 18.
We next studied the nitrosation of a disaccharide oxime.
The preparation of lactose oxime has only been described
once.[60] We found that treatment of d-lactose with hydroxyl-
amine resulted in the formation of a crystalline mixture of
nisms suggested by Freeman,[71] we propose that not only
hydroxylamine 27 but also the open-chain E- and Z-oximes
26 undergo fast reactions with NO+.
Reactions between ketoximes and NO+ result in the for-
mation of carbonyl compounds plus N2O.[71] Less frequently,
carbonyl products are also formed from aldoximes on nitro-
sation. The reactions start with an electrophilic attack of
NO+ on the oxime nitrogen (Scheme 3). The resulting N-ni-
trosooxime splits off a proton to form a N-nitrosooximate. If
there are OH groups in the molecule, the two subsequent
competing reactions are probably directed by steric effects.
Clearly, in the case of ketoximes the attack of the N-nitro-
sooximate-OÀ ion on the C=N double bond is faster than
502
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Chem. Eur. J. 2006, 12, 499 –509

Nitrosation of Sugar Oximes
FULL PAPER
Scheme 3. Proposed nitrosation mechanisms for w-hydroxyaldoximes and w-hydroxyketoximes.
the intramolecular reaction with the OH group. The result-
ing oxaziridine undergoes intramolecular ring-opening with
the OH group to form a semiacetal+N2O (Scheme 3b). In
the case of, for example, aldoximes (oximes of aldoses), on
the other hand, the intramolecular attack of an OH group
on the C=N double bond of the N-nitrosooximate to afford
a 2-substituted 1-hydroxydiazene-2-oxide seems to be faster
than the formation of a N-nitrosoxaziridine (Scheme 3a).
Details of the mechanisms await further investigations.
To test whether ketoximes of carbohydrates would react
with NO+ according to Scheme 3b, we prepared d-fructose
oxime (29).[73–75] We found that nitrosation of this open-
chain oxime under diverse experimental conditions resulted
in the exclusive formation of d-fructose, and so it seems un-
likely that diazene-1-olate-2-oxides could be prepared from
oximes of ketoses.
Finally, to study the influence of the configuration of the
2-OH group, we examined the nitrosation of d-mannose
oxime (30; Scheme 4).[37,76–78] According to an X-ray struc-
tural analysis, compound 30 is an open-chain E-oxime.[77]
We prepared mannose oxime 30 (yield 87%) from d-man-
nose in the manner described for compound 12. NMR spec-
tra (D2O) of 30 showed a mixture (E/Z=1.0:0.1) of the
open-chain oximes, but no trace of a pyranosyl- or furano-
sylhydroxylamine. At 238C the E/Z ratio of an aqueous so-
lution of 30 did not change over several days.
Treatment of aqueous solutions of the oxime 30 with
NaNO2/HCl afforded (after neutralization with NH3 or
NaHCO3 or KHCO3) amorphous mixtures of 2-(d-manno-
pyranosyl)diazene-1-olate-2-oxides, mannose, and some un-
identified mannose derivatives. We had problems in separat-
ing these mixtures, but neutralization with p-anisidine pro-
duced the solid p-anisidinium salt 31, which was converted
into the pure acid 32 plus p-anisidine simply by dissolution
in THF/MeOH. To the best of our knowledge, 2-glycosyl-1-
hydroxydiazene-2-oxides have not been reported in the liter-
ature until now. The large JH3,H4 and JH4,H5 coupling con-
stants of almost 10 Hz are indicative of the pyranose struc-
ture of 32. According to a report that JH1,H2 <1.5 Hz for b-
mannopyranoses and JH1,H2 >2.1 Hz for a-mannopyrano-
ses,[37] we tentatively assign b-configuration to the acid 32
(JH1,H2 ꢁ1.2 Hz). Compound 32 is only moderately soluble in
H2O and rather sensitive to acid, so when the reaction time
of the nitrosation of the mannose oxime at 0–58C in dilute
aqueous HCl was extended to more than 45 min, increasing
amounts of mannose were formed. Furthermore, during
13C NMR measurements of solutions of 32 in D2O (about
10 h at 308C) at least 2% of 32 was hydrolyzed to mannose.
+
+
À
Scheme 4. Reactions of mannose oxime with NO . a) NaNO2/HCl. b) p-Anisidine. c) THF/MeOH. d) NaHCO3. e) Me2CHCH2CH2 ONO, H2O, M
OHÀ. f) Ac2O/pyridine, 58C.
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J. C. Jochims et al.
Table 2. 1H and 13C data (also see the Experimental Section) of the diazene-2-glycosyl-1-olate-2-oxides (m=
multiplet, J not determined).
Neutralization of acid 32 with
NaHCO3 in H2O afforded the
crystalline and quite stable
sodium salt 33. Again, the large 13[a]
d [ppm]
J [Hz]
d [ppm]
d [ppm]
14a[b]
J [Hz]
d [ppm]
H1
5.29
J1,2
J2,3
J3,4
J4,5
J5,6
J5,6’
J6,6’
9.0
m
9.4
9.4
m
C1
C2
C3
C4
C5
C6
96.5
H1
H2
H3
H4
H5
H6
H6’
5.73
6.19
6.06
J1,2
J2,3
J3,4
J4,5
J5,6
J5,6’
J6,6’
9.0
9.5
9.8
9.8
5.3
C1
99.1
69.1
72.8
68.7
75.4
62.7
JH3,H4 and JH4,H5 coupling con-
H2
stants, of more than 9 Hz, and
H3
ꢁ3.93
ꢁ3.65
3.51
ꢁ3.65
72.1
78.5
71.7
80.8
63.2
C2
C3
C4
C5
C6
the small JH1,H2 coupling of
H4
5.83
about 0.1 Hz are in agreement
H5
ꢁ4.42
H6
H6’
3.77
5.1
12.5
4.56
4.68
3.0
12.3
with the structure of a b-pyra-
nose.
ꢁ3.88
Nitrosations of nitrogen com-
pounds have been carried out
not only with NaNO2 under H2
14b[c]
H1
17[a]
H1
H2
H3
H4
H5
H6
H6’
6.06
6.24
6.12
J1,2
J2,3
J3,4
J4,5
J5,6
J5,6’
J6,6’
9.4
C1
C2
C3
C4
C5
C6
89.5
ꢁ68.4
ꢁ74.1
ꢁ69.4
ꢁ75.0
62.7
5.84
ꢁ3.94
ꢁ3.69
3.51
ꢁ3.68
ꢁ3.92
3.76
J1,2
J2,3
J3,4
J4,5
J5,6
J5,6’
J6,6’
9.4
m
ꢁ9.7
ꢁ9.4
m
C1
C2
C3
C4
C5
C6
94.1
71.7
78.7
71.6
81.1
63.2
ꢁ9.4
ꢁ9.7
ꢁ9.7
2.9
4.6
12.5
H3
H4
H5
H6
H6’
acidic conditions but also with
5.90
À
alkyl nitrites RO NO in the
ꢁ3.60
presence of bases.[61,79] We
found that nitrosations of d-
mannose oxime (30) with iso-
pentyl nitrite in aqueous solu-
tions of CsOH or KOH resulted
in the isolation of the cesium or
4.58
5.8
12.5
ꢁ3.88
18[b]
H1
H2
H3
19[b]
H1
H2
H3
H4
H5
H6
H6’
6.02
5.50
5.38
J1,2
J2,3
J3,4
J4,5
J5,6
J5,6’
J6,6’
9.4
ꢁ9.4
ꢁ9.6
ꢁ9.7
4.9
C1
C2
C3
C4
C5
C6
89.0
67.3
73.2
67.6
74.5
61.6
5.32
5.65
5.33
5.23
3.91
4.19
4.28
J1,2
J2,3
J3,4
J4,5
J5,6
J5,6’
J6,6’
9.4
ꢁ9.4
ꢁ9.5
ꢁ9.5
2.3
C1
C2
C3
C4
C5
C6
94.7
68.4
72.7
67.2
75.0
61.5
potassium salts 34 and 35 of 1- H4
5.21
H5
H6
H6’
ꢁ3.96
hydroxy-2-(a-d-mannofurano-
syl)diazene-2-oxide (Scheme 4).
X-ray structural analyses to
verify the anomeric configura-
tions of these compounds are
planned, but we have so far
been unable to prepare suitable
crystals, so the configurations of
4.28
2.0
12.5
4.9
12.6
4.22
20[d]
H1
H2
H3
H4
H5
22[a]
H1
H2
H3
H4
5.35
5.54
5.32
J1,2
J2,3
J3,4
J4,5
J5,6
J5,6’
J6,6’
8.2
9.4
9.4
9.8
4.7
C1
C2
C3
C4
C5
C6
100.9
69.4
72.9
67.8
72.8
61.5
5.22
3.92
3.59
3.72
3.47
4.07
J1,2
J2,3
J3,4
J4,5e
J4,5a
J5e,5a
9.0
ꢁ9.2
ꢁ9.2
5.5
10.9
ꢁ11.1
C1
C2
C3
C4
C5
97.2
72.0
78.7
71.4
70.1
5.20
ꢁ3.66
H5a
H5e
these compounds are still not H6
absolutely certain, although the
4.23
2.3
12.5
H6’
4.08
small coupling constants of 2–
3 Hz between H3 and H4 and
the larger couplings of 9 Hz be-
25[a]
H1
H2
H3
H4
H5a
H5e
28[a]
H1
H2
H3
H4
H5
H6
5.78
3.93
3.64
J1,2
J2,3
J3,4
J4,5a
J4,5e
J5a,5e
9.3
ꢁ9.3
ꢁ9.2
ꢁ11.0
5.3
C1
C2
C3
C4
C5
94.7
71.7
78.9
71.3
70.2
5.32
3.99
3.79
–
–
–
J1,2
J2,3
J3,4
J4,5
J5,6
9.0
m
m
m
m
C1
C2
C3
C4
C5
C6
96.4
71.8
78.1
71.3
80.1
62.6
tween H4 and H5 in these com-
pounds are consistent with cor-
responding coupling constants
in other mannofuranoses.[80–82]
ꢁ3.72
3.53
4.10
ꢁ11.3
J5,6’
m
The
relatively
high-field 32[a]
33[a]
H1
H2
H3
H4
H5
H6
H6’
13C NMR shifts of 101.1 ppm
for C1 in both 34 and 35 ex-
clude the possibility of open-
chain compounds (compare, for
instance, the open-chain oximes
30: (E)-C1 d=155.4, (Z)-C1
d=155.0 ppm; Table 2).[83] Sup-
port for the assignment of the
H1
H2
H3
H4
H5
H6
H6’
5.58
4.47
J1,2
J2,3
J3,4
J4,5
J5,6
1.2
3.1
ꢁ9.6
ꢁ9.7
2.3
C1
C2
C3
C4
C5
C6
97.4
72.0
75.2
68.8
82.1
63.4
5.37
4.43
J1,2
J2,3
J3,4
J4,5
J5,6
J5,6
J6,6
ꢁ0.1
2.3
ꢁ9.4
ꢁ9.2
ꢁ2.3
6.2
C1
C2
C3
C4
C5
C6
93.9
72.3
75.6
69.0
81.8
63.5
ꢁ3.82
ꢁ3.77
3.69
3.74
ꢁ3.60
3.97
ꢁ3.82
3.58
3.94
ꢁ3.81
J5,6
J6,6
’
’
6.3
12.7
’
’
12.5
34[a]
H1
35[a]
H1
H2
H3
H4
H5
H6
H6’
5.66
4.84
4.43
4.32
3.59
3.77
3.68
J1,2
J2,3
J3,4
J4,5
J5,6
6.6
4.3
2.3
9.0
2.7
C1
C2
C3
C4
C5
C6
101.1
75.8
74.1
84.4
71.4
65.5
5.66
4.85
4.43
4.32
3.95
3.77
3.69
J1,2
J2,3
J3,4
J4,5
J5,6
6.6
4.3
2.7
9.0
2.7
C1
C2
C3
C4
C5
C6
101.1
75.8
74.1
84.4
71.5
65.5
a-configurations to compounds H2
H3
34 and 35 is provided by the
H4
molecular rotations (34: [M]2D3 =
H5
+281.3 (H2O) and 35: [M]2D3 =
H6
H6’
J5,6’
J6,6’
5.1
12.5
J5,6’
J6,6’
5.1
12.1
+283.6 (H2O)) and the large
3JH1,H2 coupling constants of
6.6 Hz.[80,86] According to Hud-
sonꢁs isorotation rule, large pos-
itive molecular rotations point
[a] D2O; T=308C; internal ref. Me3Si(CH2)3SO3Na. [b] CDCl3; T=208C; internal ref. TMS. [c] C6D6; T=
208C; internal ref. TMS. [d] CDCl3/C6D6 =2:1; T=208C; internal ref. TMS.
504
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 499 –509

Nitrosation of Sugar Oximes
FULL PAPER
to a-configurations of d-mannofuranoses.[84,85] For salt 35, a
small long-range coupling of approximately 0.3 Hz between
H-1 and H-4 was observed. A similar long-range coupling
has been reported for N-acetyl-a-l-rhamnofuranosyl-
amine.[86] Acetylation of 35 with Ac2O/pyridine at 58C af-
forded a pentaacetate, the 1H and 13C NMR spectra of
which were identical to those reported for penta-O-acetyl-a-
d-mannofuranose.[80]
ture had been stirred at 238C for 12 h the solvent was evaporated from
the clear solution and the oily residue (essentially open-chain oxime) was
stirred at 238C in MeOH (20 mL) for 80 h, after which a colorless crystal-
line powder of the pure title compound 12 (15.92 g, 82%) was filtered off
and washed with MeOH (5 mL) and with Et2O. Evaporation of the
mother liquor left an oil, which consisted of 12 and the E and Z forms
(10 and 11) of d-glucose oxime (10/11/12 1:5:2, by 1H NMR). Stirring of
the oil in MeOH (7 mL) for 3 days afforded a second fraction of pure
crystalline 12 (2.63 g, 14%). M.p. 120–1228C (decomp 147–1498C)
(ref. [37]: decomp. 143–1458C); [a]2D5 =À7.73 (c=1.1, H2O, 5 min after
dissolution) (ref. [37]: [a]D25 =À10.7 (c=1.1, H2O, 2 min after dissolu-
tion)); 1H NMR (D2O, 25 8C): d=4.19 (d, J=9.3 Hz; H-1), 3.40 (t, J=
9.3 Hz; H-2), 3.34–3.54 (m; H-3–H-5), 3.72 (dd, J=5.7, 12.3 Hz; H-6),
3.90 (dd, J=2.1, 12.3 Hz; H-6’); 13C NMR (D2O, 20 8C): d=93.6 (C-1),
79.8, 79.4, 72.2, 72.1 (C-2–C-5), 63.6 (C-6). After this had been allowed to
stand at 258C for 5 h the spectrum showed a mixture of the oximes 10,
11, and the hydroxylamine 12 (integral ratio 0.9:0.4:1.0).
Until now, the mechanistic reason for the different results
of nitrosation of mannose oxime under acidic and basic con-
ditions has not been clear. One probably has to apply the
+
À
Curtin–Hammett principle to
a
À
protonated R CH=N
+
À
(NO)OH and a deprotonated R CH=N (NO)O transition
state.[86] At present we are studying nitrosations of other car-
bohydrate oximes under basic conditions. Preliminary results
show that these nitrosations proceed in a similar manner to
that found for mannose oxime 30.
1H NMR (D2O, 20 8C): d=7.51 (d, J=7.0 Hz; (E)-H-1), 6.88 (d, J=
6.5 Hz; (Z)-H-1), 4.39 (t, J=7.0 Hz; (E)-H-2), 5.00 (t, J=6.5 Hz; (Z)-H-
2), 3.95 (m; (E)-,(Z)-H-3); 13C NMR (D2O, 25 8C): d=154.5, 154.1
((E)-,(Z)-C-1).
Ammonium 2-(b-d-glucopyranosyl)diazene-1-olate-2-oxide (13): HCl
(1m, 120 mL) was added at 08C to a solution of 12 (19.52 g, 100 mmol) in
H2O (100 mL).
A solution of NaNO2 (7.25 g, 105 mmol) in H2O
Experimental Section
(100 mL) was added dropwise at 08C with stirring over the course of 1 h.
Addition of aqueous NH3 (25%, 12 mL) and evaporation of the solvent
under reduced pressure afforded a pale yellow solid, which according to
General: Solvents were dried by standard methods. All reactions were
carried out with exclusion of moisture. Spectrometers used: 1H
(400.1 MHz) and 13C (100.6 MHz) NMR spectra: JEOL JNM-LA-400 FT
NMR system. Internal reference SiMe4 (TMS) or Me3Si(CH2)3SO3Na
(PSIL); d scale in ppm; coupling constants J in Hz. Signal assignments
were supported by 1H spin–spin decoupling and CH correlation experi-
ments. IR spectra: Perkin–Elmer FTIR 1600 spectrometer; UV spectra:
Perkin–Elmer Lambda 19 UV/Vis/near-IR spectrometer; solvent H2O.
Optical rotations: Perkin–Elmer 241 polarimeter.
1
the H NMR spectrum consisted of a mixture of 13 (76%) and a- and b-
d-glucopyranose (6% and 15%), together with trace amounts of (E)-
and (Z)-d-glucoseoximes 10 and 11, and of at least five other sugars (not
identified). The product was dissolved in warm H2O (60 mL) containing
a few drops of concentrated aqueous NH3. On addition of MeOH
(160 mL) compound 13 started to crystallize. After 48 h at 58C, fine col-
orless prisms (15.64 g, 65%) of title compound 13 were isolated by filtra-
tion and washed with small amounts of MeOH and Et2O. Decomposition
with gas evolution and blackening 193–1988C; [a]2D5 =À17.9 (c=1.0,
H2O); 1H NMR (D2O, 20 8C): d=5.29 (d, J=9.0 Hz; H-1), ꢁ3.93 (m;
H-2), ꢁ3.88 (m; H-6), 3.77 (dd, J=5.1, 12.5 Hz; H-6’), 3.65 (m; H-3,
H-5), 3.51 (t, J=9.4 Hz; H-4); 13C NMR (D2O, 20 8C): d=96.5 (C-1), 80.8
(C-5), 78.5 (C3), 72.1 (C-2), 71.6 (C-4), 63.2 (C-6); UV (H2O): lmax (e)=
254 nm (9816mÀ1 cmÀ1); elemental analysis calcd for C6H15N3O7 (241.2):
C 29.87, H 6.27, N 17.43; found: C 29.77, H 6.21, N 17.44.
Single-crystal X-ray analysis: Single-crystal X-ray diffraction analysis was
performed with an Enraf–Nonius CAD4 four-circle diffractometer with
graphite monochromated MoKa radiation (l=0.71073 Š) in the q range
of 2–268 with a scan width w (8) of 0.5+0.35tanq for both structures.
The structures were solved by direct methods and refined by full-matrix,
least-squares analyses with use of SHELX-97-2 software.[87] Non-hydro-
gen atoms were refined with anisotropic displacement parameters and all
hydrogen atoms were placed in calculated positions and refined isotropi-
cally.
(Z)-1-Methoxy-2-(2,3,4,6-tetra-O-benzoyl-b-d-glucopyranosyl)diazene-2-
oxide (14a) and N-methoxy-N-nitroso-2,3,4,6-tetra-O-benzoyl-b-d-gluco-
pyranosylamine (14b): A suspension of 13 (2.41 g, 10 mmol), NaHCO3
(2.52 g, 30 mmol), and Me2SO4 (3.78 g, 30 mmol) in H2O (10 mL) was
stirred at 238C for 24 h. After evaporation of the solvent the semisolid
residue was suspended in hot pyridine (30 mL). PhCOCl (11.25 g,
80 mmol) was added at 58C. After 24 h at 58C the suspension was diluted
with H2O. The mixture was repeatedly extracted with CHCl3, and the
combined organic extracts were washed with HCl (1m), then with aque-
ous NaHCO3, and finally with H2O. Evaporation of the solvent afforded
a yellow resin, which crystallized on scratching under Et2O (40 mL).
After 12 h at 58C a colorless crystalline powder (4.23 g, 65%) was isolat-
ed by filtration. Recrystallization from boiling EtOH (340 mL) furnished
colorless needles of 14a (3.64 g, 56%) suitable for X-ray diffraction anal-
ysis. M.p. 194–1958C; [a]D25 =+17.8 (c=1.2, CHCl3); 1H NMR (CDCl3):
d=3.98 (OMe), 4.42 (m; H-5), 4.56 (dd, 3J=5.3, 2J=12.3 Hz; H-6), 4.68
(dd, 3J=3.0, 2J=12.3 Hz; H-6’), 5.73 (d, 3J=9.0 Hz; H-1), 5.83 (t, 3J=
9.8 Hz; H-4), 6.06 (dd, J=9.5, 9.8 Hz; H-3), 6.19 (dd, J=9.0 Hz, 9.5 Hz;
H-2), 7.26–8.02 (m, 20H; phenyl); 13C NMR (CDCl3, 208C): d=95.1
(C-1), 61.9 (OMe), 62.7 (C-6), 68.7 (C-4), 69.1 (C-2), 72.8 (C-3), 75.4
(C-5), 128.4–129.9 (o,m,p-C, aryl), 133.2, 133.5, 133.6, 133.7 (iC, aryl),
164.2, 165.0, 165.7, 166.1 (CO); IR (CCl4): n˜ =1741(vs), 1266(vs),
1245(s), 1101(s), 1090(vs), 1069(vs), 1027 cmÀ1 (s); UV (MeCN): lmax
(e)=230 (5477.4), 199 nm (5433.6mÀ1 cmÀ1); elemental analysis calcd for
C35H30N2O11 (654.61): C 64.21, H 4.62, N 4.28; found: C 64.20, H 4.70, N
4.34. Evaporation of the ethereal mother liquor of the first crystallization
CCDC-264902 (14a) and CCDC-264903 (18) contain the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Crystal structure data for 14a: Formula C35H30N2O11 (Mr =654.61); crys-
tal dimensions 0.2”0.2”0.5 mm; orthorhombic; space group P212121; a=
9.371(3), b=16.733(3), c=21.421(4) Š; V=3359(1) Š3; Z=4; 1calcd
=
1.294 gcmÀ3
; 2qmax =24.0798; T=183 K; 6252 independent reflections
(Rint =0.068), of which 2817 were above 2s(F2); R1=0.2457; wR2=
0.1268 with I>2s(I); Rs =0.0601; GoF=0.97; D1max =0.25 eŠÀ3; D1min
=
À3
À0.26 eŠ
.
Crystal structure data for 18: Formula C15H22N2O11 (Mr =406.4); crystal
dimensions 0.3”0.3”0.5 mm; orthorhombic; space group P212121; a=
5.723(1), b=17.650(3), c=19.666(4) Š; V=1886.4(7) Š3; Z=4; 1calcd
=
1.359 gcmÀ3
; 2qmax =31.5758; T=153 K; 3915 independent reflections
(Rint =0.022), of which 2762 were above 2s(F2); R1=0.1065; wR=0.1841
3
3
À3
with I>2s(I); Rs =0.0479; GoF=1.00; D1max =0.30 eŠ
; D1min =
À3
À0.31 eŠ
.
N-Hydroxy-b-d-glucopyranosylamine (12): A suspension of NH2OH·HCl
(10.43 g, 150 mmol) in MeOH (100 mL) was stirred at 238C for 15 min.
The resulting clear solution was cooled to 58C and Me3COK (15.71 g,
140 mmol) was added in portions. After the mixture had been stirred at
238C for 30 min, KCl was filtered off and washed with MeOH (50 mL).
d-Glucose (18.02 g, 100 mmol) was added to the filtrate. After the mix-
Chem. Eur. J. 2006, 12, 499 –509
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
505

J. C. Jochims et al.
of 14a left a brown syrup consisting of small amounts of 14a and of at
least two other carbohydrates (1H NMR). The main component 14b was
isolated by column chromatography (silica gel 60 (Fluka), eluent Et2O/
hexane 1:1) as a moderately stable and not completely pure and noncrys-
tallized pale yellow powder. Elemental analysis calcd for C35H30N2O11
(654.61): C 64.21, H 4.62, N 4.28; found: C 64.62, H 4.87, N 4.02. The
1H NMR spectrum (CDCl3) of 14b showed partial decomposition within
1 h into a mixture of three new compounds (not identified).
Compound 14b: 1H NMR (C6D6): d=6.06 (d, 3J=9.4 Hz; H-1), 6.24 (t,
3J=9.4 Hz; H-2), 6.12 (t, 3J=9.7 Hz; H-3), 5.90 (t, 3J=9.7 Hz; H-4), 3.60
(m; H-5), 4.58 (dd, 3J=2.9, 2J=12.5 Hz; H-6), 4.28 (dd, 3J=4.6, 2J=
12.5 Hz; H-6’), 3.49 (OMe), 6.76–8.17 (m, 20H; Ph); 13C NMR (C6D6,
208C): d=89.5 (C-1), 75.0, 74.1 (C-5,3), 69.4, 68.4 (C-4,2), 65.1 (br,
OMe), 62.7 (C-6), 127.9–133.5 (Ph), 164.8, 165.3, 165.9, 166.1 (C=O).
Na2SO4. Evaporation of the solvent left a yellow crystalline residue
(4.04 g, 99%) consisting of 19 and of the isomer 18 (ratio 1.00:0.23;
1H NMR). Recrystallization from boiling EtOH (40 mL) afforded (at
58C) pale yellow needles (3.13 g, 77%; 19/18=1.00:0.10). Another crys-
tallization from EtOH furnished colorless needles of the pure title com-
pound 19. Compounds 18 and 19 were also separated by column chroma-
tography (silica gel 60, Fluka; eluent hexane/CHCl3 1:1).
Compound 19: M.p. 148–1498C; [a]2D5 =À24.1 (c=1.0, CHCl3); 1H NMR
(CDCl3): d=2.00, 2.03, 2.05, 2.10 (acetyl), 3.92 (m; H-5), 4.12 (OMe),
4.19 (dd, 3J=2.3, 2J=12.6 Hz; H-6), 4.28 (dd, 3J=4.9, 2J=12.6 Hz; H-6’),
5.23 (t, 3J=9.5 Hz; H-4), 5.35 (d, 3J=9.2 Hz; H-1), 5.33 (t, 3J=9.5 Hz;
H-3), 5.65 (t, 3J=9.4 Hz; H-2); 13C NMR (CDCl3): d=20.4, 20.5, 20.5,
20.7 (acetyl-Me), 61.5 (C-6), 62.0 (OMe), 67.2 (C-4), 68.4 (C-2), 72.7
(C-3), 75.0 (C-5), 94.7 (C-1), 168.4, 169.2, 170.2, 170.6 (C=O); IR (CCl4):
n˜ =1752(vs), 1506(s), 1438(m), 1368(s), 1236(vs), 1208(vs), 1061(vs),
1035(s), 1020 cmÀ1 (s); UV (MeCN): lmax (e)=239 nm (7520mÀ1 cmÀ1); el-
emental analysis calcd for C15H22N2O11 (406.35): C 44.33, H 5.46, N 6.90;
found: C 44.41, H 5.40, N 6.87.
N-Methoxy-N-nitroso-2,3,4,6-tetra-O-acetyl-b-d-glucopyranosylamine
(18): d-Glucose (1.80 g, 10 mmol) and MeONH2·HCl (1.00 g, 12 mmol)
were dissolved in warm pyridine (15 mL). After the mixture had been
kept at 238C for 24 h, the solvent was evaporated and the oily residue
was dissolved in H2O (20 mL). NaHCO3 (1.05 g, 12.5 mmol) was added
(CO2 evolution). Evaporation of the solvent afforded a colorless syrup of
the O-methyloximes 15 and 16 (ratio 1.0:0.2). 1H NMR (D2O): d=7.53
(d, 3J=6.7 Hz; (Z)-H-1), 6.88 (d, 3J=6.6 Hz; (E)-H-1), 4.39 (t, 3J=
6.7 Hz; (Z)-H-2), 4.92 (t, 3J=6.6 Hz; (E)-H-2), 3.85 (s; (Z)-OMe), 3.88
(s; (E)-OMe), 3.57–3.95 (m, 10H); 13C NMR (D2O): d=153.6 ((Z)-C-1),
154.5 ((E)-C-1), 64.1–79.8 (12C).
1-(2,3,4,6-Tetra-O-acetyl-b-d-glucopyranosyloxy)-2-phenyldiazene-2-ox-
ide (20): A solution of cupferron (1.56 g, 10 mmol) in DMSO (10 mL)
was cooled to 58C. After addition of a-acetobromoglucose (2.06 g,
5 mmol) the mixture soon solidified. After the system had been allowed
to warm to 238C over 5 h and stirred at 238C for 24 h, H2O (50 mL) was
added to the orange-brown solution. Extraction with Et2O (3”50 mL),
drying of the extracts over Na2SO4, and evaporation of the solvent under
reduced pressure afforded a dark red syrup, which was dissolved in Et2O
(20 mL). After 24 h at À158C, compound 20 (0.94 g, 40%) was isolated
by filtration as a brownish crystalline powder. Evaporation of the filtrate
afforded a brown oil, which according to its NMR spectra consisted of
20, azoxybenzene, and a- and b-2,3,4,6-tetra-O-acetyl-d-glucopyranose.[88]
The crude 20 was dissolved in boiling ethyl acetate (4 mL). After addi-
tion of hexane (4 mL) and keeping at 58C for 3 days, almost colorless
prisms (0.70 g) of title compound 20 were filtered off. M.p. 148–1508C;
[a]2D3 =+27.3 (c=1.0, CHCl3); 1H NMR (CDCl3/[D6]benzene=2:1): d=
7.89 (d, 3J=7.4 Hz; 2H; phenyl), 7.22–7.32 (m, 3H; phenyl), 5.54 (dd,
3J=9.4, 8.2 Hz; H-2), 5.35 (d, 3J=8.2 Hz; H-1), 5.32 (t, 3J=9.4 Hz; H-3),
5.20 (dd, 3J=9.8, 9.4 Hz; H-4), 4.23 (dd, 3J=4.7, 2J=12.5 Hz; H-6), 4.08
(dd, 3J=2.3, 2J=12.5 Hz; H-6’), 3.66 (m; H-5); 13C NMR (CDCl3/
[D6]benzene=2:1): d=170.4, 170.1, 169.2, 169.0 (C=O), 143.4, 131.7,
129.0, 121.5 (phenyl), 100.9 (C-1), 72.9, 72.8 (C-3,5), 69.4 (C-2), 67.8
(C-4), 61.5 (C-6), 20.4–20.5 (4”CH3); IR (CCl4): n˜ =1762(vs), 1487(s),
1441(m), 1367(s), 1315(w), 1244(vs), 1226(vs), 1212(vs, shoulder),
1152(w), 1113(m, shoulder), 1082(vs), 1055(s), 1037(vs), 1013 cmÀ1 (s);
UV (H2O): lmax (e)=254 (10310), 198 nm (13647mÀ1 cmÀ1); elemental
analysis calcd for C20H24N2O11 (468.41): C 51.28, H 5.17, N 5.98; found: C
51.17, H 5.21, N 6.12.
The crude mixture of 15+16 was dissolved in H2O (10 mL). HCl (1m,
12 mL) was added at 0–58C and a solution of NaNO2 (0.76 g, 11 mmol)
in H2O (10 mL) was added dropwise over 30 min. After the mixture had
been stirred at 238C for a further 10 min, aqueous NH3 (25%, 3 mL) was
added. Evaporation of the solvent afforded the crude N-methoxy-N-ni-
troso-b-d-glucopyranosylamine (17) contaminated with small amounts of
a- and b-d-glucopyranose. The product was taken up in MeOH (10 mL)
and THF (10 mL). After 24 h at 238C the suspension was filtered.
Evaporation of the filtrate afforded a syrup, which was dissolved in
MeOH (10 mL). Evaporation of the solvent furnished 17 as a yellow
amorphous solid (1.83 g, 77%) still containing about 2% of a- and b-d-
glucopyranose and other impurities. 1H NMR (D2O): d=5.84 (d, 3J=
9.4 Hz; H-1), 3.91–3.98 (m; H-2, H-6, OCH3), 3.76 (dd, 3J=5.8, 2J=
12.5 Hz; H-6’), 3.65–3.72 (m; H-3, H-5), 3.51 (dd, 3J=9.4, 9.7 Hz; H-4);
13C NMR (D2O): d=94.1 (C-1), 81.1 (C-5), 78.74 (C-3), 71.72 (C-2), 71.6
(C-4), 67.9 (OMe), 63.2 (C-6).
The crude 17 was taken up in pyridine (10 mL) and Ac2O (5 mL). After
12 h at 58C and a further 12 h at 238C the solvent was evaporated. The
oily residue was repeatedly extracted with CHCl3/HCl (1m)/H2O. Evapo-
ration of the combined organic extracts afforded a yellow oil, which was
crystallized at À158C from THF/pentane (7:10 mL) to furnish the title
compound 18 as a yellow crystalline powder (2.62 g, 65%). Recrystalliza-
tion at 508C from EtOH (1 g from 20 mL EtOH) afforded prisms suit-
able for X-ray diffraction analysis. M.p. 132–1348C; dissolved in CDCl3,
d-Xylose oximes 21: These compounds were prepared from d-xylose
(15.01 g, 100 mmol) in the manner described for 12. After evaporation of
MeOH and drying at 808C/10À1 torr for 20 h, 21 was obtained as a pale
yellow syrup (16.35 g, 99%). [a]2D5 =À0.3 (c=1.2, H2O; no change over 5
compound 18 decomposed within
a
few days; [a]2D5 =+33.0 (c=1.0,
1
3
CHCl3); 1H NMR (CDCl3): d=6.02 (d, 3J=9.4 Hz; H-1), 5.50 (t, 3J=
months); H NMR (D2O, 25 8C): d=7.54 (d, J=6.3 Hz; (E)-H-1, integral
3
3
3
3
1.00), 6.90 (d, J=6.3 Hz; (Z)-H-1, integral 0.22), 4.12 (d, J=9.0 Hz; H-1
of N-hydroxy-b-d-xylopyranosylamine, integral 0.03), 4.38 (dd, 3J=6.3,
5.8 Hz; (E)-H-2), 4.97 (dd, 3J=6.3, 4.9 Hz; (Z)-H-2), 3.61–3.80 (m;
(E)-,(Z)-H-3,4,5,5’); 13C NMR (D2O, 25 8C): d=154.3 ((E)-C-1), 155.0
((Z)-C-1), 72.4 ((E)-C-2), 68.0 ((Z)-C-2), 74.7 ((E)-C-3), 74.2 ((Z)-C-3),
73.7 ((E)-C-4), 74.1 ((Z)-C-4), 65.3 ((E)-C-5), 65.2 ((Z)-C-5).
9.4 Hz; H-2), 5.38 (t, J=9.4 Hz; H-3), 5.21 (t, J=9.7 Hz; H-4), 4.28 (dd,
3J=4.9, 2J=12.5 Hz; H-6), 4.22 (dd, 3J=2.0, 2J=12.5 Hz; H-6’), 3.96 (m;
H-5), 3.86 (OMe), 2.10, 2.07, 2.03, 1.96 (OCCH3); 13C NMR (CDCl3): d=
170.6, 170.2, 169.3, 168.8 (C=O), 89.0 (C-1), 74.5 (C-5), 73.2 (C-3), 67.6
(C-4), 67.3 (C-2), 65.5 (OMe), 61.6 (C-6); UV (MeCN): lmax (e)=233 nm
(5500mÀ1 cmÀ1); elemental analysis calcd for C15H22N2O7 (406.4): C 44.33,
H 5.46, N 6.90; found: C 44.32, H 5.35, N 6.80.
Ammonium 2-(b-d-xylopyranosyl)diazene-1-olate-2-oxide (22): The mix-
ture of compounds 21 (1.65 g, 10 mmol) was dissolved in H2O (20 mL),
and HCl (1m, 14 mL) was added at 08C. A solution of NaNO2 (0.83 g,
12 mmol) in H2O (30 mL) was added dropwise with stirring over the
course of 30 min. After the mixture had been stirred for a further 10 min,
aqueous NH3 (25%, 1 mL) was added. Evaporation of the solvent under
reduced pressure furnished a pale yellow solid (2.73 g). The 1H NMR
spectrum of the crude product showed a mixture of 22 (ꢁ79%), a- and
b-d-xylopyranose (ꢁ8% each), and trace amounts of at least four other
sugars (not identified) but no starting material 21. The product was dis-
solved in warm H2O (10 mL). On addition of MeOH (20 mL) compound
(Z)-1-Methoxy-2-(2,3,4,6-tetra-O-acetyl-1-deoxy-b-d-glucopyranosyl)di-
azene-2-oxide (19): Me2SO4 (3.78 g, 30 mmol) was added to a suspension
of 13 (2.41 g, 10 mmol) and NaHCO3 (2.52 g, 30 mmol) in H2O (10 mL).
After the mixture had been stirred at 238C for 48 h the solvent was
evaporated under reduced pressure. The resulting yellow syrup was taken
up in hot pyridine (30 mL). The suspension was cooled to 58C and Ac2O
(10 mL) was added. After the mixture had been stirred at 238C for 24 h
the solvent was evaporated and the solid residue was dissolved in CHCl3
and HCl (1m). The mixture was repeatedly extracted with CHCl3 and the
combined organic extracts were washed with H2O and dried over
506
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 499 –509

Nitrosation of Sugar Oximes
FULL PAPER
22 started to crystallize. After 48 h at 58C the pure title compound 22
(1.08 g, 51%) was filtered off as a colorless crystalline powder. Decomp.
(blackening) above 808C; [a]2D5 =À55.6 (c=1.0, H2O); 1H NMR (D2O):
d=5.22 (d, 3J=9.0 Hz; H-1), 3.92 (t, 3J=9.1 Hz; H-2), 3.59 (t, 3J=
9.3 Hz; H-3), 3.72 (m; H-4), 3.47 (t, 2J,3Jꢁ10.9 Hz; H-5a), 4.07 (dd, 3J=
5.5, 2J=11.3 Hz; H-5e); 13C NMR (D2O): d=97.2 (C1), 78.7 (C3), 72.0
(C2), 71.4 (C4), 70.1 (C5); UV (H2O): lmax (e)=254 nm (4788mÀ1 cmÀ1);
elemental analysis calcd for C5H13N3O6 (211.2): C 28.44, H 6.21, N 19.90;
found: C 28.38, H 5.97, N 19.41. Compound 22 turned brown in the
course of a few months at 238C.
ring over the course of 20 min. Benzhydrylamine (0.55 g, 3 mmol) was
added to the acidic clear solution. Evaporation under reduced pressure
afforded a colorless solid (1.98 g), which was dissolved in hot H2O
(20 mL) and EtOH (20 mL). Crystallization at 58C afforded colorless,
fine needles (1.28 g, 75%). To remove traces of EtOH the product was
suspended in H2O (10 mL). Evaporation under reduced pressure furnish-
ed the pure title compound 28. Decomposition with gas evolution and
blackening 180–2008C; [a]2D3 =+6.9 (c=1.0, H2O); 1H NMR (D2O,
308C): d=7.42–7.52 (m, 10H; phenyl), 5.72 (s; NCH), 5.32 (d, 3J=
9.0 Hz; H-1), 4.49 (d, 3J=7.8 Hz; H-1’), 4.01–3.73 (m, 10H; H-2 (3.99),
H-4’ (3.94), H-3 (3.79), H-4,5,5’,6,6’,6’’,6’’’), 3.67 (dd, 3J=3.5, 9.8 Hz; H-
3’), 3.57 (dd, 3J=7.8, 9.8 Hz; H-2’); 13C NMR (D2O, 30 8C): d=139.4,
132.0, 131.7, 129.8 (phenyl), 105.6 (C-1’), 96.4 (C-1), 80.1 (C-5), 79.7 (C-
5’), 78.1 (C-3), 77.2 (C-4’), 75.3 (C-3’), 73.7 (C-2’), 71.8 (C-2), 71.3 (C-4),
63.7, 62.6 (C-6,6’), 60.6 (NCH); UV (H2O): lmax (e)=256 (9100), 198 nm
(25000mÀ1 cmÀ1); elemental analysis calcd for C25H35N3O12 (569.6): C
52.72, H 6.19, N 7.38; found: C 52.82, H 5.82, N 7.32.
d-Fructose oxime (29):[73–75] This compound was prepared from d-fructose
(18.02 g, 100 mmol) in the manner described for the preparation of 12.
The crude oily product consisted of a mixture of the Z and E forms of 29
(ratio 1.0:0.9; 1H NMR). Crystallization from MeOH (30 mL) afforded a
colorless powder of the pure Z isomer 29 (18.36 g, 94%). In aqueous so-
lution slow ZQE equilibration took place. After 5 days at 238C an equi-
librium Z/Eꢁ1:1 was reached. 1H NMR (D2O, 25 8C): d=5.28 (d, 3J=
2.3 Hz; (Z)-H-3), 4.32 (s, 2H; (Z)-H-1), 3.92 (dd, 3J=2.2, 8.4 Hz; (Z)-H-
4), 3.83 (dd, 3J=2.7, 2J=11.7 Hz; (Z)-H-6), 3.77 (m; (Z)-H-5), 3.64 (dd,
3J=6.2, 2J=11.7 Hz; (Z)-H-6’), 4.67 (d, 3J=2.8 Hz; (E)-H-3), 4.52 (d,
2J=14.8 Hz; (E)-H-1), 4,37 (d, 3J=14.8 Hz; (E)-H-1’), ꢁ3.76–3.85 (m;
(E)-H-4,5,6), ꢁ3.65 (m; (E)-H-6’); 13C NMR (D2O; 258C): d=164.1
((Z)-C-2), 162.8 ((E)-C-2), 74.4 ((E)-C-4), 74.1 ((Z)-C-4), 73.7 ((E)-C-5),
73.6 ((Z)-C-5), 72.5 ((E)-C-3), 69.1 ((Z)-C-3), 65.7, 65.6 ((Z,E)-C-6), 62.7
((Z)-C-1), 57.5 ((E)-C-1). Nitrosation of the oxime 29 in the manner de-
scribed for 12 exclusively furnished d-fructose.
N-Methoxy-N-nitroso-2,3,4-tri-O-acetyl-b-d-xylopyranosylamine
(25):
This compound was prepared from d-xylose (1.51 g, 10 mmol) and
MeONH2·HCl (1.00 g, 12 mmol) in the manner described for 18. The d-
xylose O-methyloxime 23[52–54] was obtained as a moderately stable pale
yellow syrup (ratio Z/E forms 1.0:0.2). 1H NMR (D2O): d=7.55 (d, 3J=
6.3 Hz; (Z)-H-1), 6.91 (d, 3J=6.2 Hz; (E)-H-1), 4.89 (t, 3J=5.5 Hz; (E)-
H-2), 4.38 (t, 3J=5.8 Hz; (Z)-H-2), 3.88 ((E)-OMe), 3.86 ((Z)-OMe),
3.59–3.84 (m, 8H; (E)-,(Z)-H-3 to H-5); 13C NMR (D2O): d=154.9 ((E)-
C-1), 153.9 ((Z)-C-1), 74.6, 73.6, 72.2, 65.2, 64.0 ((Z)-C-2 to C-5, (Z)-
OMe), 74.1, 73.9, 68.3, 65.1, 64.4 ((E)-C-2 to C-5, (E)-OMe). The N-me-
thoxy-N-nitroso-b-d-xylopyranosylamine (24) was obtained as a brownish
solid contaminated with small amounts of a- and b-d-xylose (ca. 8%), 23
(ca. 2%), and other impurities (ca. 4%). 1H NMR (D2O): d=5.78 (d,
3J=9.3 Hz; H-1), 3.93 (t, 3Jꢁ9.3 Hz; H-2), 3.64 (t, 3J=9.2 Hz; H-3), 3.72
(m; H-4), 3.53 (t, 2,3Jꢁ11 Hz; H-5a), 4.10 (dd, 3J=5.3, 2J=11.3 Hz; H-
5e), 3.99 (OMe); 13C NMR (D2O): d=94.7 (C-1), 78.9 (C-3), 71.7 (C-2),
71.3 (C-4), 70.2 (C-5), 67.9 (OMe). Acetylation of 24 afforded a pale
yellow solid, which was crystallized from hot EtOH (25 mL) to give pale
yellow needles (2.06 g, 62%) of title compound 25. Another crystalliza-
tion from EtOH furnished long, pale yellow needles. M.p. 123–1258C;
[a]2D3 =À1.7 (c=1.0, CHCl3); 1H NMR (CDCl3): d=5.92 (d, 3J=9.0 Hz;
3
3
3
H-1), 5.44 (t, Jꢁ9.1 Hz; H-2), 5.37 (t, Jꢁ9.3 Hz; H-3), 5.10 (m, Jꢁ5.5,
ꢁ10.5 Hz; H-4), 4.28 (dd, 3J=5.5, 2J=11.5 Hz; H-5e), 3.86 (OCH3), 3.52
(dd, 3Jꢁ10.5, 2J=11.5 Hz; H-5a), 2.08, 2.06, 1.96 (CH3); 13C NMR
(CDCl3): d=89.6 (C-1), 67.4 (C-2), 72.8 (C-3), 68.5 (C-4), 65.1 (C-5), 65.5
(OMe), 168.9, 169.8, 170.2 (C=O), 20.4, 20.6, 20.7 (CH3); IR (CCl4): n˜ =
1764(vs), 1505(m), 1424(m), 1369(s), 1241(vs), 1217(vs), 1121(m),
1087(m), 1035 cmÀ1 (s); UV (MeCN): lmax (e)=234 nm (5000mÀ1 cmÀ1);
elemental analysis calcd for C12H18N2O9 (334.3): C 43.11, H 5.43, N 8.38;
found: C 43.16, H 5.42, N 8.21.
d-Mannose oxime (30):[37, 76–78] This compound was prepared from d-man-
nose (18.02 g, 100 mmol), NH2OH·HCl (10.43 g, 150 mmol), and
Me3COK (15.71 g, 140 mmol) in the manner described for the prepara-
tion of 12, except that after addition of d-mannose the mixture was stir-
red at 58C for 3 days. Filtration and washing of the residue with MeOH
and Et2O afforded colorless crystals (19.40 g, 100%), which were dis-
solved in hot H2O (100 mL). Addition of MeOH (100 mL) and keeping
at 58C for 48 h furnished colorless prisms of title compound 30 (16.90 g,
87%, E/Z=1.0:0.1).[77] M.p. 183–1858C (decomp.) (ref. [37]: m.p. 1848C;
ref. [77]: m.p. 188–1838C). [a]D23 =+6.3 (c=1.0, H2O, 5 min after dissolu-
tion) (ref. [37]: [a]2D5 =+7.0 (c=1.0, H2O, 3 min after dissolution));
1H NMR (D2O, 30 8C): d=7.58 (d, 3J=7.0 Hz; (E)-H-1), 6.97 (d, 3J=
6.7 Hz; (Z)-H-1), 4.97 (dd, 3J=6.7, 7.4 Hz; (Z)-H-2), 4.28 (dd, 3J=7.0,
8.2 Hz; (E)-H-2), 3.95 (m; (Z)-H-3), 3.93 (dd, 3J=8.2, 1.1 Hz; (E)-H-3),
d-Lactose oximes 26 and 27:[60] These compounds were prepared from d-
lactose·H2O (36.03 g, 100 mmol), NH2OH·HCl (17.38 g, 250 mmol) and
Me3COK (26.93 g, 240 mmol) in MeOH (170 mL) in the manner de-
scribed for compound 12, except that the reaction mixture was stirred at
238C for 8 days. Filtration afforded the oxime (35.73 g, 98%) contaminat-
ed with ꢁ2% of d-lactose. The product was dissolved in hot H2O
(70 mL). After filtration and addition of hot EtOH (350 mL) the mixture
was kept at 58C for 3 days. Filtration afforded a crystalline mixture
(23.23 g, 65%) of the E- and Z-oximes 26 and the hydroxylamine 27.
M.p. 183–1858C (decomp.) (ref. [60]: m.p. 183–1858C); [a]2D3 (c=1.0,
H2O)=+27.8 (at 238C 10 min after dissolution) to +10.2 (at 238C
10 days after dissolution) (ref. [60]: [a]2D2 (c=1, H2O)=+38.3 (5 min after
dissolution) to +15.5 (25 h after dissolution)); 1H NMR (D2O, 30 8C)
(10 min after dissolution: (E)-26/(Z)-26/27ꢁ0.3:1.0:0.01); 26 days after
dissolution: (E)-26/(Z)-26/27ꢁ5.3:1.0:2.3: d=7.61 (d, 3J=5.9 Hz; (E)-H-
3
2
3.85 (dd, J=2.3, J=11.7 Hz; (E)-H-6), 3.77 (m; (E)-H-4, (E)-H-5), 3.67
(m; (E)-H-6’); 13C NMR (D2O, 30 8C): d=155.4 (m; (E)-C-1), 155.0 (m;
(Z)-C-1), 73.5 ((E)-C-4), 73.2 ((E)-C-3), 72.2 ((Z)-C-3), 71.8 ((E)-C-5),
71.4 ((E)-C-2), 66.1 ((Z)-C-6), 65.8 ((E)-C-6).
1-Hydroxy-2-(b-d-mannopyranosyl)diazene-2-oxide (32): Slow (45 min)
addition of a solution of NaNO2 (0.70 g, 10 mmol) in H2O (10 mL) to a
cooled (0–38C) stirred suspension of 30 (1.95 g, 10 mmol) in HCl (0.5m,
20 mL) afforded an acidic clear solution, which was quickly neutralized
by addition of p-anisidine (1.23 g, 10 mmol, crushed powder). After the
mixture had been stirred at 238C for 30 min the solvent was evaporated
under reduced pressure. The brownish amorphous residue essentially
consisted of the p-anisidinium salt 31. 1H NMR (D2O, 30 8C): d=5.42 (d,
3J=0.8 Hz; H-1), 4.44 (dd, 3J=0.8, 1.9 Hz; H-2), 3.96 (dd, 3J=2.4, 2J=
12.5 Hz; H-6), 3.72–3.86 (m; H-3,4,6’), 3.59 (m; H-5), 7.05 (d, J=9.2,
2H), 7.25 (d, J=9.2 Hz; 2H; aryl); 13C NMR (D2O, 30 8C): d=160.4,
129.3, 125.5, 118.0 (aryl), 94.7 (C-1), 72.3 (C-2), 75.5 (C-3), 69.0 (C-4),
81.9 (C-5), 63.5 (C-6), 58.4 (OCH3).
3
1), 6.95 (d, J=5.9 Hz; (Z)-H-1), 5.03 (dd, 3J=5.8, 4.7 Hz; (Z)-H-2), 4.56
3
3
3
(dd, J=6.6, 5.9 Hz; (E)-H-2), 4.52 (d, J=7.9 Hz; (Z)-H-1’), 4.49 (d, J=
7.8 Hz; (E)-H-1’), 4.45 (d, 3J=7.8 Hz; 27: H-1’), 4.22 (d, 3J=9.0 Hz; 27:
H-1), 4.07 (dd, J=2.7, 4.7 Hz; (Z)-H-3), 3.52–3.98 (m; other H atoms of
3
the E and Z form, and of 27), 3.45 (dd, 3J=9.4, 9.0 Hz; 27: H-2);
13C NMR (D2O, 30 8C): d=154.8, 154.6 ((E)-,(Z)-C-1), 106.0, 105.6
((E)-,(Z)-C-1’), 93.5 (27: C-1), 82.5, 81.0, 80.7, 78.7, 78.1, 78.0, 77.9, 77.8,
75.3, 74.0, 73.9, 73.8, 73.7, 73.6, 73.0, 72.1, 71.8, 71.3, 71.2, 68.5, 64.8, 64.7,
63.8, 63.7, 63.4, 62.9.
Diphenylmethylammonium 4-O-(b-d-galactopyranosyl)-b-d-glucopyrano-
syldiazene-1-olate-2-oxide (28): HCl (1m, 3 mL) was added to a cooled
(0–58C) suspension of 26+27 (1.08 g, 3 mmol) in H2O (3 mL). A solution
of NaNO2 (0.21 g, 3 mmol) in H2O (5 mL) was added dropwise with stir-
The crude product was suspended in MeOH (55 mL). After 5 min of ul-
trasonic irradiation at 208C, THF (40 mL) was added. The mixture was
kept at 58C for 48 h. Filtration afforded a colorless powder (1.42 g). In
order to remove NaCl the crude product was suspended in H2O (10 mL).
Chem. Eur. J. 2006, 12, 499 –509
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
507

J. C. Jochims et al.
After 5 min of ultrasonic irradiation at 208C the suspension was kept at
58C for 24 h. Filtration furnished title compound 32 as a colorless
powder (1.11 g, 50%). Decomposition with gas evolution 170–1808C;
[a]2D3 =+52.7 (c=1.0, H2O); 1H NMR (D2O, 30 8C): d=5.58 (d, 3J=
1.2 Hz; H-1), 4.47 (dd, 3J=1.2, 3.1 Hz; H-2), 3.97 (dd, 3J=2.3, 2J=
12.7 Hz; H-6), ꢁ3.81 (m; H-3, H-6’), 3.69 (dd, 3J=9.7, 9.8 Hz; H-4),
ꢁ3.60 (ddd, 3J=2.3, 6.3, 9.8 Hz; H-5); 13C NMR (D2O, 30 8C): d=97.4
(C-1), 72.0 (C-2), 75.2 (C-3), 68.8 (C-4), 82.1 (C-5), 63.4 (C-6); UV
(H2O): lmax (e)=230 nm (5417mÀ1 cmÀ1); elemental analysis calcd for
C6H12N2O7 (224.2): C 32.14, H 5.40, N 12.50; found: C 32.08, H 5.34, N
12.36.
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[3] T. B. Cai, X. Tang, J. Nagorski, P. G. Brauschweiger, P. G. Wang,
Bioorg. Med. Chem. 2003, 11, 4971–4975.
[4] L. K. Keefer, Pharm. News 2000, 7, 27–32.
[5] J. E. Saavedra, P. J. Shami, L. Y. Wang, K. M. Davies, M. N. Booth,
M. L. Citro, L. K. Keefer, J. Med. Chem. 2000, 43, 261–269.
[6] L. K. Keefer, Chemtech 1998, 28, 30–35.
[7] S. R. Hanson, T. C. Hutsell, L. K. Keefer, D. L. Mooradian, D. J.
Smith, Adv. Pharmacol. 1995, 34, 383–398.
[8] L. J. Ignarro, Nitric Oxide: Biology and Pathobiology, Academic
Press, 2000.
Sodium 2-(b-d-mannopyranosyl)diazene-1-olate-2-oxide (33): Compound
32 (1.12 g, 5 mmol) was added to a cold (0–58C) solution of NaHCO3
(0.42 g, 5 mmol) in H2O (10 mL). After 5 min of ultrasonic irradiation
the almost clear solution was filtered. On addition of MeOH (20 mL)
and THF (20 mL) the filtrate became turbid. After 2 months at 0–58C
colorless prisms of title compound 33 (0.77 g, 63%) were isolated by fil-
tration. Decomposition with gas evolution 222–2308C; [a]2D5 =+23.2 (c=
1.0, H2O); 1H NMR (D2O, 30 8C): d=5.37 (d, 3Jꢁ0.1 Hz; H-1), 4.43 (dd,
[9] D. L. H. Williams, Org. Biomol. Chem. 2003, 1, 441–449.
[10] X. Wu, X. Tang, M. Xian, P. G. Wang, Tetrahedron Lett. 2001, 42,
3779–3782.
[11] L. K. Keefer, Annu. Rev. Pharmacol. Toxicol. 2003, 43, 585–607.
[12] Y.-C. Hou, A. Janczuk, P. G. Wang, Curr. Pharm. Des. 1999, 5, 417–
441.
[13] J. E. Saavedra, D. L. Mooradian, K. A. Mowery, M. H. Schoenfisch,
M. L. Citro, K. M. Davies, M. E. Meyerhoff, L. K. Keefer, Bioorg.
Med. Chem. Lett. 2000, 10, 751–753.
[14] A. K. Tyagi, D. A. Cooney, Adv. Pharmacol. Chemother., Vol. 20,
Academic Press, New York, 1984, pp. 69–121.
3
3
3Jꢁ0.1, 2.3 Hz; H-2), ꢁ3.77 (H-3), 3.74 (t, Jꢁ9.4 Hz; H-4), 3.58 (ddd, J
ꢁ2.3, 6.2, 9.0 Hz; H-5), 3.94 (dd, 3Jꢁ2.3, 2Jꢁ12.5 Hz; H-6), ꢁ3.81 (H-
6’); 13C NMR (D2O, 30 8C): d=93.9 (C-1), 72.3 (C-2), 75.6 (C-3), 69.0
(C-4), 81.8 (C-5), 63.5 (C-6); UV (H2O): lmax (e)=253 nm
(7970mÀ1 cmÀ1); elemental analysis calcd for C6H11N2NaO7 (246.2): C
29.27, H 4.50, N 11.38; found: C 29.18, H 4.65, N 11.10.
[15] A. K. Tyagi, D. A. Cooney, Cancer Res. 1980, 40, 4390–4397.
[16] H. N. Jayaram, D. A. Cooney, Cancer Treat. Rep. 1979, 63, 1095–
1108.
Cesium 2-(a-d-mannofuranosyl)diazene-1-olate-2-oxide (34): Isopentyl
nitrite (3.52 g, 30 mmol), and then a solution of CsOH·H2O (1.85 g,
11 mmol) in H2O (5 mL), were added at 58C to a suspension of com-
pound 30 (1.96 g, 10 mmol) in MeOH (20 mL). Stirring at 58C for 24 h,
filtration and washing of the residue with MeOH and Et2O furnished a
colorless powder (3.00 g, 84%), which was dissolved in H2O (30 mL).
After addition of MeOH (300 mL) and keeping at 58C for 3 days, color-
less fine needles of title compound 34 (2.10 g, 59%) were isolated by fil-
tration and washed with MeOH and Et2O. Decomposition with evolution
of gas and blackening 198–2038C; [a]2D3 =+79.0 (c=1.0, H2O); 1H NMR
(D2O, 30 8C): d=5.66 (d, 3J=6.6 Hz; H-1), 4.84 (dd, 3J=6.6, 4.3 Hz; H-
2), 4.43 (dd, 3J=4.3, 2.3 Hz; H-3), 4.32 (dd, 3J=2.3, 2J=9.0 Hz; H-4),
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2
3.95 (m; H-5), 3.77 (dd, 3J=2.7, J=12.5 Hz; H-6), 3.68 (dd, 3J=5.1, 2J=
12.5 Hz; H-6’); 13C NMR (D2O): d=101.1 (C-1), 75.8 (C-2), 74.1 (C-3),
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Potassium 2-(a-d-mannofuranosyl)diazene-1-olate-2-oxide (35): With
KOH (0.62 g, 11 mmol) in place of CsOH·H2O the procedure for the
preparation of 34 afforded the K salt 35 as a crystalline colorless powder
(2.31 g, 88%). Decomposition with evolution of gas and blackening 212–
2158C; [a]2D3 =+108.1 (c=1.0, H2O); 1H NMR (D2O): d=5.66 (dd, 3J=
6.6, 4Jꢁ0.3 Hz; H-1), 4.85 (dd, 3J=6.6, 4.3 Hz; H-2), 4.43 (dd, 3J=4.3,
4
3
2.7 Hz; H-3), 4.32 (ddd, Jꢁ0.3, J=2.7, 9.0 Hz; H-4), 3.95 (m; H-5), 3.77
(dd, 3J=2.7, 2J=12.1 Hz; H-6), 3.69 (dd, 3J=5.1, 2J=12.1 Hz; H-6’);
13C NMR (D2O): d=101.1 (C-1), 75.8 (C-2), 74.1 (C-3), 84.4 (C-4), 71.5
(C-5), 65.5 (C-6); UV (H2O): lmax (e)=253 nm (9237mÀ1 cmÀ1); elemental
analysis calcd for C6H11KN2O7 (262.3): C 27.48, H 4.23, N 10.68; found:
C 27.52, H 4.28, N 10.45. Acetylation of 35 with Ac2O/pyridine at 58C af-
1
forded a pentaacetate, the H and 13C NMR spectra of which were identi-
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