Glucosaminides proceeding from levoglycosenone

Article abstract of DOI:10.1134/S1070428011110182

The possibility was studied of using levoglycosenone in the synthesis of N-(glucosen-2-yl) aminides. New glucosaminides were obtained containing the residues of L-a, isopinocampheol, borneol, and (-)-(1S,2R,3S,7S,8R)-4,4- dimethyl-3-nitro-9,11-dioxatricyc

Full text of DOI:10.1134/S1070428011110182

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 11, pp. 1750−1754. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © L.Kh. Faizullina, M.M. Iskakova, Sh.M. Salikhov, M.G. Safarov, F.A. Valeev, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 11, pp. 1712−1715.
Glucosaminides Proceeding from Levoglycosenone
L. Kh. Faizullinaa,b, M. M. Iskakovab, Sh. M. Salikhova, M. G. Safarovb, and
F. A. Valeeva
aInstitute of Organic Chemistry, Russian Academy of Sciences, Ufa, 450054 Russia
е-mail: lfajzullina@yandex.ru
bBashkir State University, Ufa, 450054 Russia
Received February 8, 2011
Abstract—The possibility was studied of using levoglycosenone in the synthesis of N-(glucosen-2-yl)
aminides. New glucosaminides were obtained containing the residues of L-а, isopinocampheol, borneol, , and
(–)-(1S,2R,3S,7S,8R)-4,4-dimethyl-3-nitro-9,11-dioxatricyclo[6.2.1.02,6]-undec-5-en-7-ol.
DOI: 10.1134/S1070428011110182
The application of unsaturated carbohydrates in the
glucosylation reactions is attractive for it provides a pos-
sibility to avoid the superfluous operations with protective
groups. Besides the lack of hydroxy groups permits a hope
of increasing the efficiency of the process due to reduced
sterical hindrances and to the increased solubility of the
glycoside in organic solvents which is important for its
possible further modification.
Yet in the presence of the catalytic quantity of
50% water solution of HBr in dichlororethane the
isopinocampheol reacted with oxazoline I (Scheme 2).
In the 1Н NMR spectrum of compound IV the proton
Н1 gave rise to a singlet at 5.45 ppm in contrast to the
analogous proton in the initial oxazoline I that appeared
as a doubpet at 6.36 ppm, J 7.1 Hz. These findings indi-
cate the cis-position of the substituents at the С1 and С2
atoms.Apparently at the action of HBr 1,2-trans-glycosyl
bromide was formed accompanied with the first inver-
sion of the configuration at С1. Then the bromine atom is
replaced by the alkoxide anion with the second inversion
in the acetal center resulting in 1,2-cis-glucosaminide IV.
In extension of study [1] we investigated the
glucosylation opportunities of oxazoline I obtained
from the levoglycosenone; compounds of this class were
known to easily convert at treating with alcohols into
1,2-trans-glucosaminides [2].
The attempt to convert oxazoline I into methylacetal
by boiling in methanol failed and resulted in the metha-
nolysis of the acetoxy group (Scheme 1).
In a similar way the reactions of L-menthol and
compound III [3] with oxazoline I afforded 1,2-cis-
glucosaminides V and VI.
The low yields of glycosides prompted us to estimate
the efficiency of the alternative glucosylation procedure
with the use of triacetate VII obtained by the treatment of
1,6-anhydro-5-amino-2,3,4-trideoxy-β-D-glucopyranose
[4] with acetic anhydride in the presence of sulfuric acid
[1].
Scheme 1.
OAc
O
O
C
CH3OH
Ph
+
N
I
The reactions of L-menthol and isopinocampheol
with triacetate VII in dichloromethane in the presence
of a stoichiometric amount of SnCl4 furnished in good
yields 1,2-cis-glucosaminides VIII and IX. The yield in
the reaction with borneol was somewhat lower, and it
OH
O
O
Δ
AcOCH3
+
C
Ph
N
II, 65%
1750

GLUCOSAMINIDES PROCEEDING FROM LEVOGLYCOSENONE
1751
Scheme 2.
H
NO2
H
H
NO2
HO
O
H
OAc
O
OAc
HO
O
O
O
O
III
O
I
O
Bz
N
H
Bz
N
H
IV, 38%
VI, 31%
HO
OAc
OH
O
O
O
O
+
C
Ph
N
Bz
N
H
II, 34%
V, 30%
Scheme 3.
OAc
OAc
O
O
O
O
NHAc
NHAc
HO
VIII, 75%
HO
IX, 77%
OAc
O
OAc
NHAc
VII
HO
HO
OAc
OAc
O
O
O
O
NHAc
NHAc
XI, 28%
Xа, Xb, 50%
The comparative analysis of the parameters of 1Н and
was still worse with adamantan-2-ol. In the latter case it
is likely to occur due to the low solubility of the aglycone
in the dichloromethane (Scheme 3).
The assignement of the signals in the 1Н and 13С NMR
spectra of glycosides VIII –XI was carried out using the
spectra HHCOSY and HETCOR.
13С NMR spectra of glycoside VIII and triacetate VII
showed that at the formation of compound VIII the signal
of proton Н1 suffered an upfield shift (δ 4.77 ppm), and
the signal of atom С1 shifted downfield (δ 98.15 ppm). In
the 1Н NMR spectrum of compound VIII the proton Н1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

FAIZULLINA et al.
1752
gives rise to a doublet at 4.77 ppm, 3J1–2 4.7 Hz indicating
the 1,2-cis-position of the substituents. Consequently, the
asymmetrical center С1 possesses the R-configuration.
The established spectral regularities are also observed
in the spectra of glucosaminides IX–XI.
an appropriate alcohol in 5 ml of 1,2-dichloroethane was
added at stiring a catalytic quantity of 50% HBr solution.
The mixture was stirred at 15°С till complete conversion
of initial oxazoline (TLC monitoring). The solvent was
evaporated, the residue was subjected to chromatography.
Thus the second way proved to be more efficient for
the preparation of N-(glucosen-2-yl)amides containing
a double bond in the carbohydrate fragment. Amidogly-
cosides IV, V exhibited a positive cytotoxic effect in the
test on the cells of a number of human tumors.
(–)-(1'S,2'S,3'S,5'S)-(2,6,6-Trimethylbicyclo-[3.1.1]
hept-3-yl) 6-О-acetyl-2-benzamido-2,3,4-trideoxy-α-
D-erythro-hex-3-enopyranoside (IV). Yield 0.013 g
(38%). Colorless crystals, mp 50°С (from ethyl acetate),
Rf 0.47 (hexane– ethyl acetate, 1 : 1), [α]D20 –71.8° (с 1.0,
СНСl3). 1Н NMR spectrum, δ, ppm (СD3COCD3): 0.75 s
(3Н, СН3), 1.00 m (3Н, СН3), 1.35 s (3Н, СН3), 2.00 m
(5H, СН3, Н7'), 2.30 m (2H, Н4'), 2.91 m (1H, Н2'), 2.75 m
(2H, Н5', Н1'), 3.60 d.d (1H, Н6'А, J 6.3, J 4.1 Hz), 3.80 d
(1H, Н6'B, J 6.3 Hz), 4.02 m (1H, Н3'), 4.35 m (1Н, Н2),
4.75 t (1Н, Н5, J 4.1 Hz), 5.45 s (1Н, Н1), 5.54 m (1Н,
H3), 6.30 m (1Н, Н4), 7.45 m (3Н, Ph), 8.00 m (2Н, Ph).
13С NMR spectrum, δ, ppm: 16.23 (CH3), 16.23 (CH3),
20.71 (CH3), 26.73 (CH3), 22.59 (C7'), 34.06 (C4'), 37.61
(C6'), 44.3 (C2'), 44.60 (C1'), 46.30 (C5'), 47.2 (C2), 53.29
(C3'), 69.9 (С6), 70.1 (С5), 101.4 (С1), 123.6 (Ph), 126.86
(С3), 127.0 (С4), 127.18 (Ph), 127.81 (Ph), 131.02 (Ph),
131.25 (Ph), 133.99 (Ph), 165.68 (C=O), 172.73 (C=O).
EXPERIMENTAL
1Н and 13С NMR spectra were registered on a spec-
trometer BrukerAM-300 at operating frequencies 300.13
and 75.47 MHz respectively, internal reference TMS,
solvent СDCl3. The optical rotation angles were measured
on a polarimeter Perkin Elmer-141. Melting pints were
measured on a Koeffler heating block S 30A/G (DDR).
The analytical TLC was performed on plates Sorbfil
PTSKh-AF-A, development with anise aldehyde. The
products of syntheses were isolated by column chroma-
tography on silica gel L-40/100, 30–100 g of sorbent per
1 g of compound.
(–)-(1'R,5'R,2'S)-(2-Isopropyl-5-methylcyclo-
hexyl) 6-О-acetyl-2-benzamido--2,3,4-trideoxy-α-D-
erythro-hex-3-enopyranoside (V). We obtained 0.014 g
(30%) of glycoside V and 0.016 g (60%) of alcohol II.
Colorless crystals, mp 119°С (from ethyl acetate), Rf 0.5
(hexane–ethyl acetate, 1 : 1), [α]D20 –58.8° (с 1.0, СНСl3).
1Н NMR spectrum, δ, ppm: 0.45 d [3Н, CH(CH3)2,
J 7.0 Hz], 0.65 d [3Н, CH(CH3)2, J 7.0 Hz], 0.82 m (1H,
Н5'A), 0.85 m (1Н, Н4'A), 0.89 d (3Н, СН3), 1.00 m (1H,
Н2'A), 1.22 m (1H, Н6'), 1.30 m (1Н, Н3'), 1.52 m (1Н,
Н5'B), 1.55 m (1Н, Н4'B), 1.95 s (3H, СОCH3), 2.00 m
(1Н, Н2'B), 2.08 a (3H, NHCH3), 2.23 m [1Н, CH(CH3)2],
3.27 d.t (1H, Н1', J 4.3, J 10.6 Hz), 4.00 d.d (2Н, Н6A,
Н6B, J 6.2, J 3.6 Hz), 4.38 d (1Н, Н2, J 3.6 Hz), 4.90 m
(1Н, Н5), 5.00 d (1Н, Н1, J 4.9 Hz), 5.53 m (1H, NHCH3),
5.62 m (2Н, Н3, Н4), 6.25 d (1Н, J 6.5 Hz), 7.30 m
(3Н, Ph), 7.70 m (2Н, Ph). 13С NMR spectrum, δ, ppm:
15.68 (СН3), 20.73 (CОСH3), 21.44 [CH(CH3)2], 22.73
[CH(CH3)2], 23.15 (C5'), 26.02 (C3'), 32.01 [CH(CH3)2],
34.64 (C4'), 43.43 (C2'), 46.59 (C6'), 49.10 (C2), 65.79
(C6), 67.01 (С5), 81.54 (C1'), 97.95 (C1), 126.65 (Ph),
127.37 (С4), 127.67 (C3), 128.32 (Ph), 128.46 (Ph),
131.35 (Ph), 165.42 (C=O), 169.22 (C=O).
(–)-(3aR,5S,7aR)-(2-Phenyl-6-О-acetyl-5,7а-dihydro-
3аН-pyrano[3,2-d][1,3]oxazol-5-yl)-methyl acetate
(I) and (–)-(2S,5R,6R)-[5-(acetylamino)-6-(acetoxy)-
5,6-dihydro-2Н-pyran)-2-yl]methyl avetate (VII) were
obtained by procedure [1], (–)-(1S,2R,3S,7S,8R)-4,4-
dimethyl-3-nitro-9,11-dioxatricyclo[6.2.1.02,6]-undecen-
7-ol (III), by method [3].
(–)-(3aR,5S,7aR)-(2-Phenyl-5,7а-dihydro-3аН-
pyrano[3,2-d][1,3]oxazol-5-yl)methanol (II). A solu-
tion of 0.035 g (0.12 mmol) of oxazoline I in 4 ml of
anhydeous MeOH was boiled for 2 h. Than the solvent
was evaporated, the residue was subjected to chromatog-
raphy. Yield 0.02 g (65%). Oily substance, Rf 0.3 (ethyl
acetate–hexane, 2 : 1), [α]D20 –106.2° (с 1.0, СН2Сl2).
1Н NMR spectrum, δ, ppm (the numeration of atoms of
carbohydrate moiety is conserved): 3.70 d.d (1Н, H6А,
J 11.9, J 5.5 Hz), 3.80 d.d (1Н, H6B, J 11.9, J 2.8 Hz),
4.35 m (1Н, Н2), 4.62 d.d (1Н, Н5, J 5.5, J 2.8 Hz), 6.00 m
(1Н, H3), 6.20 m (1Н, H4), 6.36 d (1Н, H1, J 7.1 Hz),
7.48 m (3Н, Ph), 8.00 m (2Н, Ph). 13С NMR spectrum,
δ, ppm: 59.6 (С2), 64.7 (С6), 68.3 (С5), 101.8 (С1), 125.9
(С3), 128.2, 128.4, 128.6, 129.6 (Ph), 131.7 (С4), 164.0
(N=COPh).
Glucosylation of alcohols with oxazoline I. To
a solution of 1 mmol of oxazoline I and 1 mmol of
(–)-(1'S,4'R,8'S,5'S,8'S,8a'R)-(7,7-Dimethyl-8-
nitro-1,4,5,7,8,8а-hexahydro-2Н-1,4-epoxycyclo-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

GLUCOSAMINIDES PROCEEDING FROM LEVOGLYCOSENONE
1753
penta[d]oxepin-5-yl) 6-О-acetyl-2-benz-amido-2,3,4-
trideoxyhex-3-enopyranoside (VI). Yield 0.013 g
(38%), Rf 0.47 (hexane–ethyl acetate, 1 : 1), [α]D20 –71.8°
(с 1.0, СНСl3). 1Н NMR spectrum, δ, ppm: 1.01 s (3H,
CH3), 1.40 s (3H, CH3), 1.42 s (3H, CH3), 3.46 d.t (1H,
Н8'A, J 9.4, J 3.9 Hz), 3.50 m (1H, H6A), 3.51 m (1H,
H2'A), 3.85 d.d (1H, H2'B, J 6.5, J 3.4 Hz), 3.94 d (1H,
H6B, J 7.6 Hz), 4.16 m (1H, Н5'), 4.21 m (1H, Н2), 4.45 m
(1H, Н1'), 4.70 m (1H, Н5), 4.72 d (1H, Н8'), 5.31 d (1H,
H1, J 5.0 Hz), 5.53 s (1H, Н4'), 5.72 d (1H, Н6', J 2.4 Hz),
5.75 m (2H, Н3, Н4), 7.50 m (3Н, Ph), 7.78 m (2H, Ph).
13С NMR spectrum, δ, ppm: 20.78 (CH3), 26.77 (CH3),
26.91 (CH3), 47.31 (C7'), 47.63 (C8А), 66.16 (C2), 70.02
(C6), 70.33 (C2'), 70.57 (C5), 71.33 (C5'), 74.22 (C1'),
97.41 (C8'), 101.73 (C1), 104.05 (C4'), 124.26 (C3),
127.03, 128.53, 131.28, 131.78 (Ph), 131.71 (C4), 134.89
(C5'А), 135.16 (C6'), 166.58 (C=O), 167.05 (C=O).
J 6.7 Hz], 0.90 d [3H, CH(CH3)2, J 6.7 Hz], 0.92 m (1H,
Н2'А), 0.96 m (1H, Н5'А), 1.21 m (1H, Н6'), 1.37 m (1H,
Н3'), 1.61 m (1H, H5'B), 1.68 m (1H, H4'B), 1.95 m (1H,
H2'B), 2.00 s (3H, NHCOCH3), 2.08 s (3H, OCOCH3),
2.22 m [1H, CH(CH3)2], 3.45 m (1H, Н1'), 4.13 m (2H,
H6A,6B), 4.20 m (1H, Н2), 4.45 m (1H, Н5), 4.73 d (1H, Н1,
J 6.6 Hz), 5.53 m (1H, NH), 5.72 d.d (1H, Н3, J 10.1 Hz),
5.83 d.d (1H, H4, J 10.1 Hz). 13С NMR spectrum, δ,
ppm: 15.59 (CH3), 20.78 (COCH3), 21.02 [CH(CH3)2],
22.31 [CH(CH3)2], 23.07 (C5'), 23.43 (NHCOCH3), 25.13
[CH(CH3)2], 31.56 (C3'), 34.39 (C4'), 40.89 (C2'), 47.78
(C6'), 49.61 (C2), 66.05 (C6), 72.38 (C5), 77.41 (C1'),
97.46 (C1), 126.65 (C3), 128.18 (C4), 169.97 (C=O),
170.81 (C=O).
(1'S,2'R,S)(1,7,7-Trimethylbicyclo[2.2.1]hept-2-yl)
(6-О-acetyl-2-acetamido-2,3,4-trideoxy-α-D-erythro-
hex-3-enopyranoside (Xa, b). Yield 0.03 g (50%),
Rf 0.27 (hexane–ethyl acetate, 1 : 1). 1Н NMR spectrum,
δ, ppm: 0.80 s (3H, CH3), 0.88 s (3H, CH3), 0.92 s (3H,
CH3), 1.00 m (1H, H5'B), 1.21 m (1H, H6'B), 1.50 m (1H,
H5'A), 1.62 m (2H, H3'AB), 1.87 m (1H, H4'), 2.00 s (3H,
CH3), 2.10 s (3H, CH3), 2.13 m (1H, H6'A), 3.59 d.d (1H,
H2', J 3.6, J 8.1 Hz) [4.05 d.d (1H, H2', J 1.6, J 7.9 Hz)],1
4.17 m (2H, H6A,B), 4.40 m (2H, H5,2), 4.70 d (1H, H1,
J 3.8 Hz) [4.72 d (1H, H1, J 3.8 Hz)], 5.49 m (1H, NH),
5.83 m (2H, H3, H4). 13С NMR spectrum, δ, ppm, (Xа):
12.04 (CH3), 20.01 (CH3), 20.19 (CH3), 20.88 (CH3),
23.34 (CH3), 27.20 (C6'), 34.18 (C5'), 39.64 (C4'), 45.03
(C3'), 46.89 (C1'), 47.24 (C2), 49.49 (C7'), 66.30 (C2'),
70.72 (C6), 86.36 (C5), 100.32 (C1), 125.80 (C3), 127.56
(C4), 169.42 (C=O), 170.79 (C=O); (Xb): 13.66 (CH3),
18.90 (CH3), 19.83 (CH3), 20.88 (CH3), 23.34 (CH3),
26.63 (C6'), 28.38 (C5'), 35.87 (C4'), 44.93 (C3'), 46.63
(C1'), 47.88 (C2), 49.03 (C7'), 66.53 (C2'), 70.72 (C6),
82.19 (C5), 98.36 (C1), 125.69 (C3), 127.66 (C4), 169.54
(C=O), 170.79 (C=O).
Glucosylation of alcohols with triaxetate VII. To
a solution of 1 mmol of triacetate VII and 1 mmol of
an appropriate alcohol in 7 ml of CH2Cl2 was added
at stirring 1 mmol of SnCl4. The mixture was stirred at
15°С till complete conversion of initial compounds (TLC
monitoring). The solvent was evaporated, the residue was
subjected to chromatography.
(–)-(1'S,2'S,3'S,5'S)(2,6,6-Trimethylbicyclo-[3.1.1]
hept-3-yl) 6-О-acetyl-2-acetamido-2,3,4-trideoxy-α-
D-erythro-hex-3-enopyranoside (VIII). Yield 0.35 g
(47%), Rf 0.5 (hexane– ethyl acetate, 1:1), [α]D20 +15.7°
(с 1.0, СНCl3). 1Н NMR spectrum, δ, ppm: 0.90 s (3H,
CH3), 1.10 d (3H, CH3, J 7.4 Hz), 1.11 m (1H, H7'А), 1.21 s
(3H, CH3), 1.78 m (1H, Н1'), 1.81 m (1H, Н4'А), 1.91 m
(1H, Н5'), 2.00 s (3H, COCH3), 2.08 s (3H, COCH3),
2.09 m (1H, Н2'), 2.33 m (1H, H7'B), 2.45 m (1H, H4'B),
4.02 m (1H, Н3'), 4.18 m (2H, H6А,6B), 4.29 m (1H, Н2),
4.46 m (1H, Н5), 4.77 d (1H, H1, J 4.7 Hz), 5.70 d (1H,
NH, J 6.5 Hz), 5.84 m (2H, H3,4). 13С NMR spectrum,
δ, ppm: 20.31 (CH3), 20.88 (COCH3), 23.33 (COCH3),
23.78 (CH3), 27.42 (CH3), 33.16 (C7'), 35.65 (C4'), 38.29
(C6'), 41.28 (C1'), 41.4 (C5'), 44.3 (C2'), 47.7 (C2), 66.4
(C6), 71.3 (C5), 77.94 (C3'), 98.15 (C1), 126.30 (C3),
127.35 (C4), 169.81 (C=O), 170.82 (C=O).
(–)-Adamantan-2-yl 6-О-acetyl-2-acetamido-2,3,4-
trideoxy-α-D-erythro-hex-3- enopyranoside (XI). Yield
0.01 g (28%), Rf 0.3 (hexane– ethyl acetate, 1 : 1), [α]D20
–80° (с 1.0, СНCl3). 1Н NMR spectrum, δ, ppm: 1.20–
2.00 m (14Н, Ad), 3.80 m (1H, Н2', Ad), 4.08 d.d (1H,
H6A, J 11.5, J 5.4 Hz), 4.12 d (1H, H6B), 4.28 d.d (1H, H2,
J 3.4, J 8.2 Hz), 4.35 t (1H, H5, J 5.4, J 11.6 Hz), 4.79 d
(1H, H1, J 3.4 Hz), 5.42 d (1H, NH, J 7.8 Hz), 5.80 m
(2H, H3,4). 13С NMR spectrum, δ, ppm: 20.85 (COCH3),
23.3 (COCH3), 27.27, 27.34, 30.62, 31.26, 31.53, 33.18,
(–)-(1'R,3'R,6'S)(6-Isopropyl-1-methylcyclohex-
3-yl) 6-О-acetyl-2-acetamido-2,3,4-trideoxy-α-D-
erythro-hex-3-enopyranoside (IX). Yield 0.03 g (55%),
Rf 0.3 (hexane–ethyl acetate, 1:1). [α]D20 –155.7° (с 1.0,
1
СНCl3). Н NMR spectrum, δ, ppm: 0.78 d (3H, СH3,
J 6.7 Hz), 0.81 m (1H, Н4'А), 0.89 d [3H, CH(CH3)2,
1
Signal of isomer Xb are given in brackets..
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

FAIZULLINA et al.
1754
36.26, 36.74, 37.49 (Ad), 47.41 (С2), 66.42 (C6), 70.71
(C5), 79.49 (C2', Ad), 96.59 (C1), 125.68 (C4), 127.66
(C3), 169.60 (C=O), 170.80 (C=O).
REFERENCES
1. Faizullina, L.Kh., Spirikhin, L.V., Safarov, M.G., and
Valeev, F.A., Zh. Org. Khim., 2010, vol. 46, p. 735.
2. Qochetqov, N.Q., Bochqov, A.F., and Dmitriev, B.A., Khi-
miya uglevodov (Chemistry of Carbohydrates), Moscow,
1967, p. 520.
ACKNOWLEDGMENTS
The study was carried out under the financial support
of the Russian Foundation for Basic Research (grant
no. 08-03-97033-р_Povolzh’e a), NSh-1725.2008.3,
and Federal targeted program «Scientific and scientific-
pedagogical personnel of the innovational Russia (State
comtracy no. 14.740.11.0367).
3. Faizullina, L.Kh., Spirikhin, L.V., Zagreeva, I.A.,
Safarov, M.G., and Valeev, F.A., Butlerov Commun., 2008,
vol. 13, p. 1.
4. Tsypysheva, I.P., Valeev, F.A., Qalimullina, L.Kh.,
Salikhov, Sh.M., Shitiqova, O.V., and Safarov, M.G., Khim.
Popim. Soedin., 2004, p. 429.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011