Phosphorylation of N-glycosides derived from para-substituted aromatic amines

Article abstract of DOI:10.1007/s11172-008-0272-8

New carbohydrate-containing aminophosphoryl compounds were synthesized on the basis of glycosylamines. The reaction pathway suggested for addition of hydrophosphoryl compounds to N-glycosides was confirmed.

Full text of DOI:10.1007/s11172-008-0272-8

Russian Chemical Bulletin, International Edition, Vol. 57, No. 9, pp. 2021—2027, September, 2008
2021
Phosphorylation of Nꢀglycosides derived from paraꢀsubstituted aromatic amines
A. A. Bobrikova,a M. P. Koroteev,a A. M. Koroteev,a Yu. V. Nelyubina,b and E. E. Nifant´eva
aMoscow Pedagogical State University,
3 Nesvizhskii per., 119021 Moscow, Russian Federation.
Fax: +7 (495) 246 5790. Eꢀmail: nastenkaꢀbobrik@yandex.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6549. Eꢀmail: unelya@xrlab.ineos.ac.ru
New carbohydrateꢀcontaining aminophosphoryl compounds were synthesized on the basis
of glycosylamines. The reaction pathway suggested for addition of hydrophosphoryl compounds
to Nꢀglycosides was confirmed.
Key words: glycosylamines, azomethines, diphenylphosphinous acid, aminophosphoryl comꢀ
pounds, furanization, phosphine oxides.
Scheme 1
Easily available glycosylamines acquire evergrowꢀ
ing application for the preparation of natural glycopepꢀ
tides and their analogs, which are currently emꢀ
ployed in enzymology and medicine.1—5 It was found that
some of these compounds possess antidiabetes activity,6
suppress the cancer cells growth.7 Introducing a phosꢀ
phorus atom and combining aminophosphoryl and carboꢀ
hydrate fragments in one molecule allows one to suggest
broadening the range of biological activity in compaꢀ
rison with the starting Nꢀglycosides. The stability of
the C—P bond towards enzyme hydrolysis determines fairly
long lifetime of such compounds in organisms, i.e.,
new drugs with prolonged action can be developed on
their basis.
Glycosylamines8,9 possess many unique properties,
e.g., the ability to undergo isomerization and various rearꢀ
rangements, not characteristic of other groups of glycoꢀ
sides, which allows employing them in unusual chemical
transformations. One of such reactions is the addition of
hydrophosphoryl compounds (HPC) to the anomeric cenꢀ
ter the possibility of which has been shown by us recentꢀ
ly.10 The addition of HPC to imines represents one of the
pathways of the Kabachnick—Fields reaction whose synꢀ
thetic potential is well studied.11
Scheme 2
We suggest that this process involves the isomerization
of the glycosylamine with the formation of an azomethine
and subsequent addition of the phosphorylating agent to
the C=N bond (Scheme 1).
If the reaction follows this pathway, the ringꢀopening
of the glycosylamine molecule is the limiting step. The
rate of tautomeric transformation depends on the electron
density on the nitrogen atom, which in turn is determined
by the nature of the radical bound to the NH group
(Scheme 2).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1986—1992, September, 2008.
1066ꢀ5285/08/5709ꢀ2021 © 2008 Springer Science+Business Media, Inc.

2022
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
Bobrikova et al.
Table. 1. The main bond distances for compound 3
Therefore, in the case of Nꢀarylglycosylamines, the inꢀ
troduction to the aromatic ring of substituents conjugated
with the amino group should lead to the change in the
glycosylamine activities in this reaction.
Bond
d/Å
Bond
d/Å
P(1)—O(1)
P(1)—C(1)
P(1)—C(7)
P(1)—C(13)
1.4858(16)
1.799(2)
1.793(2)
1.821(2)
N(1)—C(13)
N(1)—C(18)
O(3)—C(21)
O(3)—C(21)
1.454(3)
1.403(3)
1.370(3)
1.418(3)
Results and Discussion
The present work deals with the synthesis of tertiary
phosphine oxides starting from pꢀanisidine and pꢀtoluiꢀ
dine Nꢀglycosides, which contain electronꢀdonating subꢀ
stituents in paraꢀposition to the amino group.
crystal of compound 3 with a chiral center C(13), only
(S)ꢀenantiomer is present. The furyl fragment is cis with
respect to the phenyl ring C(7)—C(12) and trans with reꢀ
spect to the ring C(1)—C(6) (Fig. 1). The torsion angles
C(7)—P(1)—C(13)—C(14) and C(1)—P(1)—C(13)—C(14),
which characterize the mutual arrangement of the rings
C(7)—C(12) and C(1)—C(6) with the furan ring are equal
to 58 and 173°, respectively. In turn, the dihedral anꢀ
gle between the planes of the phenyl fragments is equal
to 107°.
The nitrogen atom N(1) is characterized by a pyramiꢀ
dal configuration; the sum of angles C—N(1)—C and
C—N(1)—H is equal to 343°. The geometric parameter
describing the mutual arrangement of the phosphine oxꢀ
ide and the phenyl fragments, viz., the torsion angle
O(1)—P(1)—C(13)—N(1), has the value of 63°. Despite
the presence of appropriate proton acceptor in molecule 3,
the NH group is not involved in the hydrogen bonding.
According to the analysis of the crystal package of 3, the
strongest intermolecular contact apparently is the trifurꢀ
cate bond joining the O(1) atom with the H(19), H(2),
and H(13), the latter being the most acidic among H atꢀ
oms of the CH groups. It can be suggested that the H atom
of the NH fragment is shielded by bulky substituents, viz.,
the furyl and the phenyl rings, which considerably hinders
approach to it by the neighboring molecule.
The addition of diphenylphosphinic acid Ph2POH to
Dꢀxyloꢀ and Dꢀlyxopyranosylamines (1a,b and 2a,b) was
carried out in DMF since the glycosylamines with free
hydroxy groups have only limited solubilities in most orꢀ
ganic solvents. The process was over in 2—3 h, i.e., twice
as fast as in the case of aniline derivatives; the products
were precipitated from the reaction mixtures upon addiꢀ
tion of ethanol. Physicochemical analysis of compounds
obtained showed that in all the cases, furan derivatives 3
and 4 are formed, i.e., the attachment of the phosphorusꢀ
containing fragment is accompanied by dehydration of the
carbohydrate part of the molecules (Scheme 3).
The similar effect was observed by us earlier in the
phosphorylation of Nꢀphenylglycosylamines10 and 2ꢀamiꢀ
nonaphthaline derivatives.* It should specially be noted
that the introduction of substituents in the aromatic ring
also affects stereochemistry of the process. Whereas the
reaction product of Dꢀxylose anilide is a racemate, then in
all the other cases studied the process proceeds with the
formation of dextrorotatory isomers.
The structure of compound 3 was confirmed by the
Xꢀray diffraction analysis, which has shown that the bond
distances and the bond angles in the molecule are close to
those typical of this class of compounds (Table 1). In the
Furan derivatives 3 and 4 obtained can be of interest as
physiologically active substances,12 however, aminophosꢀ
* Unpublished data.
Scheme 3
1a: R = Me, R´ = H, R″ = OH; 1b: R = Me, R´ = OH, R″ = H;
2a: R = OMe, R´ = H, R″ = OH; 2b: R = OMe, R´ = OH, R″ = H;
3: R = Me; 4: R = OMe

Phosphorylation of glycosylamines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
2023
Scheme 4
C(4)
C(5)
C(3)
C(6)
C(2)
C(1)
C(23)
C(8)
C(22)
C(20)
O(1)
C(7)
C(24)
O(3)
P(1)
N(1)
C(21)
C(13)
C(12)
O(2)
C(8)
C(19)
C(14)
C(17)
C(16)
C(11)
C(15)
C(9)
C(10)
Fig. 1. General view of molecule 3. Hydrogen atoms are shown
only for C(13)H and NH groups.
phoryl compounds containing a carbohydrate residue in their
structures seem to be the most promising in this respect.
In order to retain the carbohydrate component in the
reaction product structures, the addition of Ph2POH to
protected glycosylamines has been performed. The addiꢀ
tion of Ph2POH to anilides of protected monosaccharides
has been described by us earlier13 and it was shown that the
process of phosphorylation occurred slowly, heating for
24—27 h in the presence of pyridine as the catalyst has
been required.
5a, 6a: R= Me, R´ = H; 5b, 6b: R = Me, R´ = CH2OAc;
5c, 6c: R = OMe, R´ = H; 5d, 6d: R = OMe, R´ = CH2OAc
Scheme 5
Phosphorylation of peracetates of glycosylamines 5a—d
was carried out in chloroform at room temperature
(Scheme 4). According to the 31P NMR spectroscopic
data, the process was complete in 3—4 h and resulted in
the formation of products 6a—d.
Under similar conditions, the reaction of Ph2POH with
mannose diꢀOꢀisopropylidene derivative was carried out
(Scheme 5). As far as we know, glycosylamines 7a,b have
not earlier been described in the literature.
To sum up, the introduction of the donor substituents
in the paraꢀposition with respect to the amino group alꢀ
lowed us to considerably accelerate this process. It was
found that when protecting groups are present in the startꢀ
ing substrates, the phosphine oxides containing a carbohyꢀ
drate fragment are the phosphorylation reaction products.
That the process stopped after addition of a hydrophosꢀ
phoryl compound also confirmed the reaction pathway
suggested.
Phosphine oxides 6 and 8 were isolated as mixtures of
diastereomers by column chromatography. Their strucꢀ
tures were confirmed by the data from NMR spectroscopy
(1H, 13C, and 31P) and elemental analysis. In the 31P NMR
spectra of the compounds synthesized, two signals with
virtually the same integral intensities or one broad signal in
the region δ 30 were recorded. In addition, doubling of
the signals for all the protons was observed in the 1H NMR
7a, 8a: R = Me; 7b, 8b: R = OMe
spectra. The cause of different stereochemistry of the phosꢀ
phorylation reaction of free and protected glycosylamines
is not yet clear enough. It is possible that in the former
case, the formation of intraꢀ and intermolecular hydrogen
bonds occurs resulting in such a spatial orientation of the

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Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
Bobrikova et al.
Table 2. Some experimental data for the phosphine oxides synthesized
Comꢀ
pound
Yield
(%)
M.p.
/°С
Found
Calculated
Molecular
formula
(%)
C
H
N
P
3
54.5
224—225
216—218
84—86
71.38
71.41
71.08
71.46
62.84
63.49
62.25
61.97
61.84
61.74
60.45
60.65
67.42
67.50
65.62
65.60
5.46
3.65
3.62
3.62
3.47
2.34
2.47
2.14
2.19
2.36
2.40
2.24
2.14
2.59
2.54
2.39
2.47
8.27
8.00
8.22
7.68
5.44
5.46
4.48
4.84
5.52
5.31
4.58
4.72
5.25
5.62
5.34
5.46
C24H22NO2P
C24H22NO3P
С30Н34NО8Р
5.72
5.45
5.50
5.87
6.04
5.74
5.99
5.84
5.97
5.79
5.84
6.93
6.84
6.92
6.85
4
47.5
59
6a
6b
6c
6d
8a
8b
49
100—102
68—70
С33Н38NО10
С30Н34NО9Р
С33Н38NО11Р
С31Н38NО6Р
С31Н38NО7Р
Р
65
52
96—98
54
62—64
64
86—88
Bruker ACꢀ200 spectrometer (200 МHz (1H), 50 МHz (13C),
32.4 МHz (31P—{1H})) in DMSOꢀd6 (3, 4) or CDCl3 (6—8)
using signals of residual protons of the deuterated solvent as the
internal standard and 85% aq. H3PO4 as the external standard.
Assignment of the proton signals were made on the basis of the
double magnetic resonance data. Silufol UVꢀ254 plates were used
for TLC in benzene—acetonitrile—hexane (4 : 2 : 1) as the solꢀ
vent system, visualization of substances on the plates was made
by charring on heating. Column chromatography was performed
on silica gel L40—100 μm using benzene—acetonitrile—hexane
(4 : 2 : 10) as the eluent. Melting points were measured in a sealed
capillary by heating at the rate of 1 deg min–1. Optical rotation
was determined on a Jasco DIPꢀ360 polarimeter for solutions
(c 0.5) in DMSO (3, 4) or CHCl3 (6—8) at 18—20 °C. Perkin—Elꢀ
mer 2400 analyzer was used to obtain elemental analysis data.
Diphenylphosphinic acid. A mixture of water (0.41 g,
22.66 mmol) with dioxane (3 mL) was added dropwise to a soluꢀ
tion of Ph2PCl (5.0 g, 22.66 mmol) in diethyl ether (50 mL) at
5—10 °C. The mixture was stirred for 30 min, the white precipiꢀ
tate that formed was filtered off, washed with ether, and dried
in vacuo. The yield was 3.89 g (85%). 31P NMR (benzene), δ: 18.3,
1JP,H = 483 Hz.
molecule, which favors a directed addition of the phosꢀ
phorylating agent. When such interactions are excludꢀ
ed by introduction of protecting groups, two isomers
are formed.
The yields, melting points, and elemental analysis data
of the phosphine oxides synthesized are given in Table 2.
In conclusion, we have shown that the introduction of
electronꢀdonating substituents conjugated with the NH
group to the aniline fragment facilitates the isomerization
of glycosylamines with the formation of imines and allows
one to carry out the phosphorylation reaction under mild
conditions (without heating and in the absence of a base),
which is important for suppression of side processes, for
example, the Amadory rearrangement,14 and increases the
yields of the target products.
In the the study performed, the confirmations of the
reaction scheme suggested by us were obtained, and new
carbohydrateꢀcontaining aminophosphoryl compounds
based on glycosylamines known for their pharmacological
properties were synthesized.7 They contain aminophosꢀ
phoryl and carbohydrate fragments and are of practical
interest from the point of view of their possible physiologiꢀ
cal activity.
Glycosylamines 1a,b, 2a,b,16,17 and 5a—d18,19 were obtained
according to the known procedures, their physicoꢀchemical charꢀ
acteristics agreed with the literature data.
Glycosylamines 7a,b (general procedure). A solution of
2,3;5,6ꢀdiꢀOꢀisopropylideneꢀDꢀmannose (2.6 g, 10 mmol) and
paraꢀanisidine (1.35 g, 11 mmol) or paraꢀtoluidine (1.18 g,
11 mmol) in ethanol was stirred for 3 h at 55 °C and cooled to
∼20 °C. Fine white crystals that precipitated were filtered off,
washed with ethanol and diethyl ether, and dried in vacuo.
Nꢀ(2,3;5,6ꢀDiꢀOꢀisopropylideneꢀβꢀDꢀmannofuranosyl)ꢀpꢀ
toluidine (7a). The yield was 3.05 g (87.5%), m.p. 145—147 °C,
Rf 0.71, [α]D –100.6. Found (%): C, 65.08; H, 7.85; N, 3.82.
C19H27NO5. Calculated (%): C, 65.31; H, 7.79; N, 4.01.
1H NMR, δ: carbohydrate part, 1.38, 1.41, 1.46, 1.55 (4 s, 4×3 H,
Me); 3.51 (dd, 1 H, C(4)H, 3JH,H(3) = 3.1 Hz, 3JH,H(5) = 8.2 Hz);
On the whole, the addition of hydrophosphoryl comꢀ
pounds to glycosylamines is a convenient preparative
method for obtaining various aminophosphoryl derivatives
of carbohydrates.
Experimental
All the experiments with the use of reagents PIII were carried
out in solvents purified and dried according to the standard proꢀ
cedures under dry argon.15 NMR spectra were recorded on a

Phosphorylation of glycosylamines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
2025
3
4.08 (d, 2 H, C(6)H, C(6)H´, JH,H(5) = 4.9 Hz); 4.43 (m, 1 H,
Phosphine oxides 6a,d and 8a,b (general procedure). A soluꢀ
tion of compound 5a—d, 6a,b (1 mmol) and Ph2POH (1 mmol)
in chloroform (5 mL) was kept for 3—4 h at 25 °C under argon
followed by concentration in vacuo, the residue was chromatoꢀ
graphed.
3
3
C(5)H, JH,H(4) = 8.2 Hz, JH,H(6, 6´) = 4.9 Hz); 4.68 (m, 1 H,
C(2)H, JH,H(3) = 5.8 Hz, JH,H(1) = 3.7 Hz); 4.78 (m, 1 H,
C(3)H, JH,H(2) = 5.8 Hz, JH,H(4) = 3.2 Hz); 4.89 (m, 1 H,
C(1)H, 3JH,H(2) = 3.7 Hz); aglycone, 2.24 (s, 3 H, Me); 6.70 (d, 2 H,
C(3)H, C(5)H, JH,H = 8.4 Hz); 7.01 (d, 2 H, C(2)H, C(6)H,
3
3
3
3
3
1ꢀCꢀDiphenylphosphorylꢀ1ꢀdeoxyꢀ1ꢀ(pꢀtoluidino)ꢀ2,3,4ꢀtriꢀ
OꢀacetylꢀDꢀxylitol (6a), Rf 0.2, [α]D –5.5. 31P NMR, δ: 30.1
(52%), 33.5 (48%). 13C NMR, δ: carbohydrate fragment,
3JH,H = 8.4 Hz).
Nꢀ(2,3;5,6ꢀDiꢀOꢀisopropylideneꢀβꢀDꢀmannofuranosyl)ꢀpꢀ
anisidine (7b). The yield was 2.74 g (75.2%), m.p. 154—156 °C,
Rf 0.63, [α]D –98.4. Found (%): C, 61.88; H, 7.15; N, 3.52.
C19H27NO6. Calculated (%): C, 62.45; H, 7.45; N, 3.83.
1H NMR, δ: carbohydrate part, 1.38, 1.41, 1.46, 1.55 (4 s, 4×3 H,
Me); 3.51 (dd, 1 H, C(4)H, 3JH,H(3) = 3.2 Hz, 3JH,H(5) = 7.9 Hz);
1
20.0—20.6 (m, 3 H3C—C(O)); 58.0 (d, C(1), JC,P = 80.6 Hz);
62.5 (s, C(5)); 69.0 (s, C(4)); 71.2 (s, C(2)); 77.0 (d, C(3),
3JC,P = 32.2 Hz); 170.2 (m, —C(O)—CH3); toluidine fragment,
24.3 (s, Me); 113.5 (s, C(2), C(6)); 117.0 (s, C(4)); 128.6 (s, C(3),
C(5)); 146.0 (s, C(1)); phosphoryl fragment, 128.1—128.5
(m, 2 C(3), 2 C(5)); 129.7—132.2 (m, 2 C(1), 2 C(4), 2 C(2),
2 C(6)). 1H NMR, δ: carbohydrate fragment, 1.85—2.08 (m,
C(O)Me); 3.37 (m, C(5)H); 3.88 (m, C(5´)H); [3.80 (m, C(5)H);
4.13 (m, (5´)H)]*; 4.42 (br.s, OH [OH]); 4.85 (m, C(2)H,
3
4.09 (d, 2 H, C(6)H, C(6)H´, JH,H(5) = 4.8 Hz); 4.44 (m, 1 H,
C(5)H, 3JH(5),H(4) = 7.9 Hz, 3JH(5),H(6,6´) = 4.8 Hz); 4.68 (m, 1 H,
3
3
C(2)H, JH,H(3) = 5.5 Hz, JH,H(1) = 3.4 Hz); 4.78 (m, 1 H,
C(3)H, JH,H(2) = 5.5 Hz, JH,H(4) = 3.2 Hz); 4.89 (m, 1 H,
C(1)H, JH,H(2) = 3.4 Hz); aglycone, 3.75 (s, 3 H, OMe); 6.75
(d, 2 H, C(3)H, C(5)H, JH,H = 9.2 Hz); 6.78 (d, 2 H, C(2)H,
3
3
3
3
[C(2)H], JH,H(1) = 3.3 Hz); 4.97 (m, C(4)H [C(4)H]); 5.39
3
3
(m, C(3)H, [C(3)H)]); 5.23 (m, C(1)H, JH,H(2) = 3.3 Hz,
C(6)H, 3JH,H = 9.2 Hz).
2JH,P = 8.8 Hz); [5.52 (m, C(1)H, JH,H(2) = 3.3 Hz, JH,P
=
3
2
Synthesis of phosphine oxides 3 (4) (general procedure).
A solution of the corresponding derivative of Dꢀxylose (1a, 2a) or
Dꢀlyxose (1b, 2b) (1 mmol) and Ph2POH (1 mmol) in DMF
(2 mL) was kept under argon for 2—3 h at 25 °C followed by
addition of ethanol (10 mL). After ~14 h, the white precipitate
that formed was filtered off, washed with ethanol and diethyl
ether, and dried in vacuo.
= 8.0 Hz)]; toluidine fragment, 2.17 (s, Me); [2.19 (s, Me)]; 5.09
(br.s, NH, [NH]); 6.37 (d, C(3)H, C(5)H, 3JH,H = 8.4 Hz); 6.52
3
(d, C(2)H, C(6)H, JH,H = 8.4 Hz); [6.45 (d, C(3)H, C(5)H,
3
3JH,H = 8.4 Hz); 6.87 (d, C(2)H, C(6)H, JH,H = 8.4 Hz)];
phosphoryl fragment, 7.40 (m, 2 C(3)H, 2 C(4)H, 2 C(5)H);
[7.60 (m, 2 C(3)H, 2 C(4)H, 2 C(5)H)]; 7.80 (m, C(2)H, C(6)H,
[C(2)H, 2 C(6)H], 3JH,P = 11.6 Hz), 8.00 (m, C(2´)H, C(6´)H,
[C(2´)H, C(6´)H], 3JH,P = 11.6 Hz).
Nꢀ[(Diphenylphosphoryl)(2ꢀfuryl)methyl]ꢀpꢀtoluidine (3),
[α]D +15.3. 31P NMR, δ: 29.0. 13C NMR, δ: 51.3 (d, N—CH—P,
1JC,P = 82.4 Hz); furan fragment, 109.7 (d, C(3), 3JC,P = 5.2 Hz);
110.5 (s, C(4)); 142.4 (s, C(5)); 149.7 (s, C(2)); toluidine fragꢀ
ment, 24.3 (s, Me); 113.4 (s, C(3), C(5)); 116.3 (s, C(2), C(6));
1ꢀCꢀDiphenylphosphorylꢀ1ꢀdeoxyꢀ1ꢀ(pꢀtoluidino)ꢀ2,3,4,6ꢀ
tetraꢀOꢀacetylꢀDꢀglucitol (6b), Rf 0.25, [α]D –4.6. 31P NMR,
δ: 27.6. 13C NMR, δ: carbohydrate fragment, 20.8—21.2
1
(m, 4 H3C—C(O)); 58.9 (d, C(1), JC,P = 78.6 Hz); 61.7
3
129.8 (s, C(4)); 144.6 (d, C(1), JC,P = 10.3 Hz); phosphoryl
(s, C(6)); 68.0 (s, C(4)); 69.8 (s, C(2)); 70.8 (s, C(5)); 71.0 (s, C(3));
170.2 (m, —C(O)—CH3); toluidine fragment, 24.3 (s, Me); 113.5
(s, C(2), C(6)); 117.4 (s, C(4)); 128.6 (s, C(3), C(5)); 146.4
(s, C(1)); phosphoryl fragment, 128.4—128.5 (m, 2 C(3), 2 C(5));
fragment, 128.5—129.4 (m, 2 C(3), 2 C(5)); 131.7—132.6 (m, 2 C(1),
2 C(4), 2 C(2), 2 C(6)). 1H NMR, δ: 5.74 (dd, 1 H, NH,
3
3JH,CH = 11.3 Hz, JH,P = 3.7 Hz); 5.95 (dd, 1 H, N—CH—P,
3JH,H = 11.3 Hz, 2JH,P = 11.7 Hz); furan fragment, 6.20 (m, 1 H,
C(4)H, 3JH,H(3) = 3.30 Hz); 6.28 (m, 1 H, C(3)H, 3JH,H(4) = 3.3 Hz,
4JH,CHP = 2.9 Hz); 7.35 (br.s, 1 H, C(5)H); toluidine fragment,
2.10 (s, 3 H, Me); 6.82 (s, 4 H, C(3)H, C(5)H, C(2)H, C(6)H);
diphenylphosphoryl fragment, 7.45—7.51 (m, 6 H, 2 C(3)H,
2 C(4)H, 2 C(5)H); 7.79 (t, 2 H, C(2)H, C(6)H, 3JH,P = 11.0 Hz);
7.97 (t, 2 H, C(2´)H, C(6´)H, 3JH,P = 11.0 Hz).
129.7—132.1 (m, 2 C(1), 2 C(4), 2 C(2), 2 C(6)). H NMR, δ:
1
carbohydrate fragment, 1.98—2.07 (m, C(O)CH3); 4.08
(m, C(6)H, [C(6)H], C(6´)H, [C(6´)H]); 4.27 (m, C(5)H); [4.31
(m, C(5)H)]; 4.73 (m, C(4)H, [C(4)H]); 5.09 (m, C(3)H,
[C(3)H]); 5.36 (m, C(2)H, 3JH,H(1) = 5.1 Hz); [5.47 (m, C(2)H,
3
2
3JH,H(1) = 5.1 Hz)]; 5.70 (m, C(1)H, JH,H(2) = 1.6 Hz, JH,P
=
= 9.2 Hz); [5.87 (m, C(1)H, 3JH,H(2) = 1.6 Hz, 2JH,P = 9.2 Hz)];
toluidine fragment, 2.18 (s, Me); [2.25 (s, Me)]; 6.61 (d, C(3)H,
C(5)H, 3JH,H = 8.1 Hz); [6.77 (d, C(3)H, C(5)H, 3JH,H = 8.1 Hz)];
7.00 (d, C(2)H, C(6)H, JH,H = 8.1 Hz); [7.02 (d, C(2)H,
C(6)H), 3JH,H = 8.1 Hz]; phosphoryl fragment, 7.35 (m, 2 C(3)H,
Nꢀ[(Diphenylphosphoryl)(2ꢀfuryl)methyl]ꢀpꢀanisidine (4),
[α]D +10.6. 31P NMR, δ: 28.9. 13C NMR, δ: 59.3 (d, N—CH—P,
1JC,P = 82.6 Hz); furan fragment, 106.7 (d, C(3), 3JC,P = 5.2 Hz);
110.6 (s, C(4)); 142.1 (s, C(5)); 152.5 (s, C(2)); anisidine fragꢀ
ment, 55.2 (s, CH3), 114.1 (s, C(3), C(5)); 115.3 (s, C(2), C(6));
3
2 C(4)H, 2 C(5)H); [7.50 (m, 2 C(3)H, 2 C(4)H, 2 C(5)H)]; 7.90
3
3
128.6 (s, C(4)); 140.8 (d, C(1), JC,P = 10.5 Hz); phosphoryl
(m, C(2)H, C(6)H, [C(2)H, C(6)H], JH,P = 11.0 Hz); 8.05
fragment, 128.0—128.4 (m, 2 C(3), 2 C(5)); 130.8—131.5 (m, 2 C(1),
(m, C(2´)H, C(6´)H, [C(2´)H, C(6´)H], 3JH,P = 11.0 Hz).
1ꢀCꢀDiphenylphosphorylꢀ1ꢀdeoxyꢀ1ꢀ(pꢀanisidino)ꢀ2,3,4ꢀtriꢀ
OꢀacetylꢀDꢀxylitol (6c), Rf 0.3, [α]D –6.2. 31P NMR, δ: 30.7
(42%), 32.6 (58%). 13C NMR, δ: carbohydrate fragment,
2 C(4), 2 C(2), 2 C(6)). 1H NMR, δ: 5.56 (dd, 1 H, NH,
3
3JH,CH = 11.1 Hz, JH,P = 3.8 Hz); 5.90 (dd, 1 H, N—CH—P,
3JH,NH = 11.1 Hz, 2JH,P = 11.6 Hz); furan fragment, 6.21 (m, 1 H,
3
4
1
C(4)H, JH,H(3) = 3.2 Hz, JH,H(5) = 1.8 Hz); 6.30 (m, 1 H,
21.8—22.2 (m, 3 H3C—C(O)); 58.0 (d, C(1), JC,P = 80.6 Hz);
3
4
C(3)H, JH,H(4) = 3.2 Hz, JH,CHP = 2.4 Hz); 7.35 (m, 1 H,
62.5 (s, C(5)); 68.1 (s, C(4)); 69.3 (s, C(2)); 73.8 (d, C(3),
3JC,P = 34.4 Hz); 170.2 (m, —C(O)—CH3); anisidine fragment,
55.8 (s, OCH3); 113.8 (s, C(2), C(6)); 117.4 (s, C(4)); 128.8
(s, C(3), C(5)); 146.6 (s, C(1)); phosphoryl fragment, 128.3—128.7
4
C(5)H, JH,H(3) = 1.8 Hz); anisidine fragment, 3.60 (s, 3 H,
OMe); 6.64 (d, 2 H, C(3)H, C(5)H 3JH,H = 8.6 Hz); 6.86 (d, 2 H,
C(2)H, C(6)H, 3JH,H = 8.6 Hz); phosphoryl fragment, 7.43—7.53
(m, 6 H, 2 C(3)H, 2 C(4)H, 2 C(5)H); 7.78 (t, 2 H, C(2)H, C(6)H,
3JH,P = 10.7 Hz); 7.98 (t, 2 H, C(2´)H, C(6´), 3JH,P = 11.0 Hz).
* Chemical shifts and spinꢀspin coupling constants for the secꢀ
ond diastereomer are given in square brackets.

2026
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
Bobrikova et al.
(m, 2 C(3), 2 C(5)); 129.7—132.4 (m, 2 C(1), 2 C(4), 2 C(2),
2 C(6)). 1H NMR, δ: carbohydrate fragment, 1.85—2.08
(m, C(O)Me); 3.80 (m, C(5)H); 3.88 (m, C(5´)H); [4.10
(m, C(5)H); 4.33 (m, (5´)H)]; 4.42 (br.s, OH, [OH]); 4.85
(m, C(2)H, [C(2)H], JH,H(1) = 6.6 Hz); 4.98 (m, C(4)H,
[C(4)H]); 5.21 (m, C(3)H); 5.29 (m, C(1)H, 3JH,H(2) = 6.6 Hz,
3JH,P = 11.0 Hz); 7.85 (m, C(2´)H, C(6´)H, [C(2´)H, C(6´)H],
3JH,P = 10.6 Hz).
1ꢀCꢀDiphenylphosphorylꢀ1ꢀdeoxyꢀ1ꢀ(pꢀanisidino)ꢀ2,3;5,6ꢀdiꢀ
OꢀisopropylideneꢀDꢀmannitol (8b), Rf 0.36, [α]D –21.5. 31P NMR,
δ: 30.9 (60%); 34.6 (40%). 13C NMR, δ: carbohydrate fragment,
3
1
26.2—26.5 (m, C(CH3)2); 52.4 (d, C(1), JC,P = 87.8 Hz); 65.5
3
2JH,P = 9.7 Hz); [5.38 (m, C(3)H); 5.52 (m, C(1)H, JH,H(2)
=
(s, C(6)); 66.7 (s, C(5)); 71.9 (s, C(3)); 75.8 (s, C(4)); 78.3
2
2
= 6.6 Hz, JH,P = 9.5 Hz)]; anisidine fragment, 3.69 (s, OCH3,
[OCH3]); 5.09 (br.s, NH, [NH]); 6.39 (d, C(3)H, C(5)H,
3JH,H = 8.8 Hz); 6.64 (d, C(2)H, C(6)H, 3JH,H = 8.8 Hz); [6.49
(d, C(3)H, C(5)H, JH,H = 8.8 Hz); 6.55 (d, C(2)H, C(6)H,
3JH,H = 8.8 Hz)]; phosphoryl fragment, 7.40 (m, 2 C(3)H,
(d, C(2), JC,P = 28.6 Hz); 111.0 (s, O(2)—C(CH3)2—O(3));
113.5 (s, O(5)—C(CH3)2—O(6)); anisidine fragment, 55.8
(s, OCH3); 114.5 (s, C(2), C(6)); 115.1 (s, C(4)); 128.6 (s, C(3),
C(5)); 149.3 (s, C(1)); phosphoryl fragment, 128.7—129.2
(m, 2 C(3), 2 C(5)); 131.7—132.6 (m, 2 C(1), 2 C(4), 2 C(2),
2 C(6)). 1H NMR, δ: carbohydrate fragment, 1.18—1.29
3
2 C(4)H, 2 C(5)H); [7.58 (m, 2 C(3)H, 2 C(4)H, 2 C(5)H)]; 7.80
3
3
(m, C(2)H, C(6)H, [C(2)H, C(6)H], JH,P = 11.6 Hz), 7.90
(m, C(CH3)2); 3.47 (m, C(5)H, [C(5)H], JH,H(4) = 6.2 Hz,
(m, C(2´)H, C(6´)H, [C(2´)H, C(6´)H], 3JH,P = 11.6 Hz).
1ꢀCꢀDiphenylphosphorylꢀ1ꢀdeoxyꢀ1ꢀ(pꢀanisidino)ꢀ2,3,4,6ꢀ
tetraꢀOꢀacetylꢀDꢀglucitol (6d), Rf 0.22, [α]D –4.0. 31P NMR,
δ: 27.3. 13C NMR, δ: carbohydrate fragment, 19.8—20.1
3JH(5),H(6) = 6.2 Hz,, JH(5),H(6´) = 6.6 Hz); 3.83 (m, C(4)H,
3
[C(4)H], 3JH,H(5) = 6.2 Hz, 3JH,H(3) = 1.7 Hz); 4.04 (m, C(6)H,
C(6´)H, [C(6)H, C(6´)H], 3JH(6),H(5) = 6.2 Hz, 3JH(6´),H(5) = 6.6 Hz);
4.34 (m, C(3)H, [C(3)H], 3JH,H(2) = 8.1 Hz, 3JH,H(4) = 1.7 Hz);
4.59 (m, C(2)H, [C(2)H], 3JH,H(3) = 8.1 Hz, 3JH,H(1) = 7.3 Hz);
1
(m, 4 H3C—C(O)); 58.9 (d, C(1), JC,P = 78.6 Hz); 62.9
3
2
(s, C(6)); 68.0 (s, C(4)); 68.8 (s, C(2)); 69.8 (s, C(5)); 70.0 (s, C(3));
170.2 (m, —C(O)—CH3); anisidine fragment, 55.8 (s, OMe);
113.5 (s, C(2), C(6)); 117.4 (s, C(4)); 128.8 (s, C(3), C(5)); 146.4
(s, C(1)); phosphoryl fragment, 128.4—128.7 (m, 2 C(3), 2 C(5));
4.69 (m, C(1)H, [C(1)H], JH,H(2) = 7.3 Hz, JH,P = 8.4 Hz);
anisidine fragment, 3.67 (s, OMe); [3.71 (s, OMe)]; 6.41
3
(d, C(3)H, C(5)H, JH,H = 9.1 Hz); [6.44 (d, C(3)H, C(5)H,
3JH,H = 9.1 Hz)]; 6.56 (d, C(2)H, C(6)H, 3JH,H = 9.1 Hz); [6.66
(d, C(2)H, C(6)H, 3JH,H = 9.1 Hz)]; phosphoryl fragment, 7.50
(m, 2 C(3)H, 2 C(4)H, 2 C(5)H, [2 C(3)H, 2 C(4)H, 2 C(5)H]);
7.69 (m, C(2)H, C(6)H, [C(2)H, C(6)H], 3JH,P = 11.0 Hz); 7.95
(m, C(2´)H, C(6´)H, [C(2´)H, C(6´)H], 3JH,P = 11.0 Hz).
1
129.7—132.1 (m, 2 C(1), 2 C(4), 2 C(2), 2 C(6)). H NMR, δ:
carbohydrate fragment, 1.78—2.04 (m, C(O)Me); 4.01
(m, C(6)H, [C(6)H], C(6´)H, [C(6´)H]); 4.07 (m, C(5)H); [4.27
(m, C(5)H)]; 4.74 (m, C(4)H, [C(4)H]); 5.08 (m, C(3)H,
[C(3)H]); 5.41 (m, C(2)H, 3JH,H(1) = 5.2 Hz); [5.57 (m, C(2)H,
3
2
3JH,H(1) = 5.2 Hz)]; 5.70 (m, C(1)H, JH,H(2) = 1.6 Hz, JH,P
=
= 9.6 Hz); [5.87 (m, C(1)H, 3JH,H(2) = 1.6 Hz, 2JH,P = 9.6 Hz)];
anisidine fragment, 3.70 (s, OMe, [OMe]); 6.44 (d, C(3)H,
C(5)H, 3JH,H = 8.9 Hz); [6.51 (d, C(3)H, C(5)H, 3JH,H = 8.9 Hz)];
6.65 (d, C(2)H, C(6)H, [C(2)H, C(6)H], 3JH,H = 8.9 Hz); phosꢀ
phoryl fragment, 7.35 (m, 2 C(3)H, 2 C(4)H, 2 C(5)H); [7.56
(m, 2 C(3)H, 2 C(4)H, 2 C(5)H)]; 7.90 (m, C(2)H, C(6)H,
Table 3. Principal crystallographic data and refining parameters
for the structure 3
Parameter
Value
Molecular formula
Molecular weight
T/K
C24H22NO3P
403.40
120
3
[C(2)H, C(6)H], JH,P = 10.7 Hz); 8.12 (m, C(2´)H, C(6´)H,
[C(2´)H, C(6´)H], 3JH,P = 10.7 Hz).
Crystal system
Space group
Z
Orthorhombic
P212121
4
1ꢀCꢀDiphenylphosphorylꢀ1ꢀdeoxyꢀ1ꢀ(pꢀtoluidino)ꢀ2,3;5,6ꢀdiꢀ
OꢀisopropylideneꢀDꢀmannitol (8a), Rf 0.3, [α]D –22.6. 31P NMR,
δ: 29.2 (45%); 35.5 (55%). 13C NMR, δ: carbohydrate fragment,
1
a/Å
b/Å
c/Å
α/deg
5.6686(12)
17.646(4)
19.960(4)
90.00
24.4—26.9 (m, C(CH3)2); 52.8 (d, C(1), JC,P = 86.7 Hz); 67.0
(s, C(6)); 69.9 (s, C(5)); 74.3 (s, C(3)); 76.1 (s, C(4)); 80.3
2
(d, C(2), JC,P = 28.7 Hz); 109.0 (s, O(2)—C(CH3)2—O(3));
109.2 (s, O(5)—C(CH3)2—O(6)); toluidine fragment, 20.2
(s, CH3); 112.3 (s, C(2), C(6)); 113.4 (s, C(4)); 128.6 (s, C(3),
C(5)); 144.0 (s, C(1)); phosphoryl fragment, 126.8—128.4
(m, 2 C(3), 2 C(5)); 131.2—132.5 (m, 2 C(1), 2 C(4), 2 C(2),
2 C(6)). 1H NMR, δ: carbohydrate fragment, 1.11—1.47
β/deg
90.00
γ/deg
90.00
1996.5(7)
1.342
V/Å3
dcalc/g cm–3
μ/cm–1
3
(m, C(Me)2); 3.47 (m, C(5)H, [C(5)H], JH,H(4) = 6.0 Hz,
1.64
3
3JH(5),H(6) = 6.3 Hz, JH(5),H(6´) = 6.5 Hz); 3.80 (m, C(4)H,
F(000)
848
[C(4)H], 3JH,H(5) = 6.0 Hz, 3JH,H(3) = 1.9 Hz); 4.05 (m, C(6)H,
C(6´)H, [C(6)H, C(6´)H], 3JH(6),H(5) = 6.3 Hz, 3JH(6´),H(5) = 6.5 Hz);
4.19 (m, C(3)H, [C(3)H], 3JH,H(2) = 8.1 Hz, 3JH,H(4) = 1.9 Hz);
4.38 (m, C(2)H, [C(2)H], 3JH,H(3) = 8.1 Hz, 3JH,H(1) = 7.4 Hz);
2θmax/deg
58
Number of measured reflections
14844
Number of independent reflections
5288
Number of reflections with I > 2σ(I)
3898
3
2
4.62 (m, C(1)H, [C(1)H], JH,H(2) = 7.4 Hz, JH,P = 8.4 Hz);
Number of refined parameters
263
toluidine fragment, 2.14 (s, Me); [2.18 (s, Me)]; 6.39 (d, C(3)H,
R1
wR2
GOF
0.0467
0.1030
1.001
3
3
C(5)H, JH,H = 8.0 Hz); [6.45 (d, C(3)H, C(5)H, JH,H
=
3
= 8.0 Hz)]; 6.79 (d, C(2)H, C(6)H, JH,H = 8.0 Hz); [6.88
(d, C(2)H, C(6)H, JH,H = 8.0 Hz)]; phosphoryl fragment,
3
Residual electron
density/e•Å–3, ρmin/ρ
0.519/–0.278
7.50 (m, 2 C(3)H, 2 C(4)H, 2 C(5)H, [2 C(3)H, 2 C(4)H,
2 C(5)H]); 7.66 (m, C(2)H, C(6)H, [C(2)H, C(6)H],
max

Phosphorylation of glycosylamines
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
2027
Xꢀray study. Clear crystals of 3 suitable for Xꢀray analysis
were obtained by the isothermic concentration of an ethanolic
solution of compound 3 at room temperature. Xꢀray analysis of
compound 3 was performed on a SMART 1000 CCD diffractoꢀ
meter (MoꢀK irradiation, graphite monochromator, ωꢀscanꢀ
ning). The structure was deciphered by the direct method and
refined by the least squares method in an anisotropic fullꢀmatrix
approximation on F 2hkl. The hydrogen atom of the NH group
was localized from the differential Fourier syntheses of the elecꢀ
tron density. Positions of the H(C) hydrogen atoms were calcuꢀ
lated geometrically. All the hydrogen atoms were refined in an
isotropic approximation by the riding model. The principal crysꢀ
tallographic data and refining parameters are given in Table 3.
All the calculations were made using the SHELXTL PLUS proꢀ
gram package.20
6. E. Truscheit, W. Frommer, B. Junge, L. Müller, D. D.
Schmidt, W. Wingender, Angew. Chem., Int. Ed. Engl., 1981,
20, 744.
7. L. Wang, C. A. Maniglia, S. L. Mella, A. C. Sartorelly, J. Med.
Chem., 1983, 26, 629.
8. H. S. Isbell, H. L. Frush, J. Org. Chem., 1958, 23, 1309.
9. G. P. Ellis, G. Honeyman, Adv. Carbohydr. Chem., 1955,
10, 95.
10. E. E. Nifant´ev, S. V. Metlitskikh, M. P. Koroteev, A. N.
Stash, V. K. Bel´skii, Zh. Obshch. Khim., 2006, 76, 1050 [Russ.
J. Gen. Chem., 2006, 76 (Engl. Transl.)].
11. R. A. Cherkasov, V. I. Galkin, Usp. Khim., 1998, 67, 940
[Russ. Chem. Rev., 1998, 67 (Engl. Transl.)].
12. B. Boduszek, Phosphorus Sulfur Silicon Relat. Elem., 1999,
144 (146), 433.
13. A. M. Koroteev, A. A. Bobrikova, M. P. Koroteev, K. A.
Lyssenko, E. E. Nifant´ev, Zh. Obshch. Khim., 2008, 78, 202
[Russ. J. Gen. Chem., 2008, 78 (Engl. Transl.)].
14. J. E. Hodge, Adv. Carbohydr. Chem., 1955, 10, 169.
15. C. Reichardt, Solvents and Solvent Effects in Organic Chemisꢀ
try, VCH, Weincheim, 1998.
This work was partially financially supported by the
Russian Federation President Council for Grants (Proꢀ
gram for the State Support of Leading Scientific Schools
of Russian Federation, Grant NShꢀ582.2008.3).
16. J. Sokolowsky, Z. Swiatacz, Rocz. Chem., 1964, 38, 1511.
17. Z. Swiatacz, A. Moczulska, Carbohydr. Res., 1984, 128, 227.
18. R. Bognar, P. Nanasi, J. Chem. Soc., 1955, 185.
19. L. Wang, T.ꢀSh. Lin, A. C. Sartorelly, J. Org. Chem., 1983,
48, 2891.
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Received April 7, 2008;
in revised form May 23, 2008