Synthesis of levoglucosenone oxazoline derivative

Full text of DOI:10.1134/S1070428010050313

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 5, pp. 768−770. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © L.Kh. Faizullina, M.G. Safarov, L.V. Spirikhin, F.A. Valeev, 2010, published in Zhurnal Organicheskoi Khimii, 2010,
Vol. 46, No. 5, pp. 772−774.
SHORT
COMMUNICATIONS
Synthesis of Levoglucosenone Oxazoline Derivative
L. Kh. Faizullinab, M. G. Safarovb, L. V. Spirikhina, and F.A. Valeeva
aInstitute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences
bGOU VPO “Bashkir State University,” Ufa, 450074 Russia
e-mail: lfajzullina@yandex.ru
Received June 25, 2008
DOI: 10.1134/S1070428010050313
Aminosugars are extensively used in the chemistry of
natural compounds for preparation of modified glycosides.
The amino derivative of levoglucosenone I [1] is a
promosing compound for the synthesis of unsaturated
glycopyranoside fused with an oxazoline ring for its further
application as a glycosylation agent [2–5].
obtained are in agreement with the published data on the
preparation of oxazolines from sugars [7].
Benzoyl derivative IV was obtained by converting
aminosugar I into hydrobromide III which was treated
with benzoyl chloride. The subsequent stages of the
opening of the 1,6-anhydro bridge in the N-benzoyl
derivative and ring closure under the action of TMSOTf
resulted in stable crystalline oxazoline VI [8].
In the 13C NMR spectrum of precursor V the signal
of “amide” carbon atom appeared at 165.1 ppm, and the
closure into the oxazoline ring led to the upfield shift of
this signal to 163.9 ppm.
Amine I necessary for the oxazoline synthesis we
prepared by the procedure previously developed [1]. One
of the most difficult stages in the planned synthesis was
the cleavage of the 1,6-anhydro bridge. Therefore this
stage was tested on a model of initial amine I. It turned
out that unlike the other levoglucosenone derivatives [6]
the 1,6-anhydro bridge in amine I cleanly opened under
the action of H2SO4–Ac2O within 3 days giving
exclusively a-anomer II. The structure of obtained
compound II is confirmed by the coupling constant
J6,5 4.0 Hz characteristic of the α-anomer. The data
In the proton spectrum the change in the coupling
constant of the signal of proton H1 at 6.34 ppm should be
mentioned that on cyclization into oxazoline grows from
4.0 to 7.1 Hz, and also the difference in the chemical
O
OAc
O
O
O
O
O
O
BzCl, Py
72%
Ac2O, H2SO4
89%
HBr, CHCl3
96%
OAc
.
NH2
NHAc
NH2 HBr
NH
Bz
II
III
IV
I
Ac2O, H2SO
470%
OAc
OAc
O
O
TMSOTf, DCE
76%
O
OAc
C Ph
N
NHAc
VI
V
768

SYNTHESIS OF LEVOGLUCOSENONE OXAZOLINE DERIVATIVE
769
solution was evaporated. Yield 0.264 g (97%).
shifts of the protons at the double bond registered as
a doublet of doublets at 6.0 ppm and a multiplet at
6.22 ppm. The coupling was observed between the
protons of acetoxymethyl group, of proton H2 with
J 11.8 and proton H5 with J5,6 6.1 and 3.8 Hz.
N-(7,8-Dioxabicyclo[3.2.1]oct-3-en-2-yl)benz-
amide (IV). In 3.25 ml of pyridine was dissolved 0.264 g
(1.3 mmol) of salt III, at 0°C 0.197 ml was added of
freshly distilled benzoyl chloride. In the course of 5 h
crystals precipitated, the reaction mixture was poured
into ice water, and the product was extracted with ethyl
acetate (3×5 ml), after evaporating the solvent the residue
was recrystallized. Yield 0.281 g (96%). White crystals,
mp 104–106°C, Rf 0.3 (ethyl acetate), [a]D20 –96.3° (C
1.0, CHCl3). 1H NMR spectrum, δ, ppm: 3.76 d.d (1H,
H6, J 6.5, 4.1 Hz), 3.88 d (1H, H6, J 6.5 Hz), 4.52 m (1H,
H2), 4.58 d.d (1H, H5, J 4.1, 4.3 Hz), 5.10 s (1H, H1),
5.26 d.d (1H, H3, J 9.6, 2.4 Hz), 6.25 d.d (1H, H4, J 9.6,
4.3 Hz), 7.48 m (2H, Ph), 7.60 t (1H, 7.3 Hz), 8.14 d
(5H, Ph), 10.9 br.s (NH). 13C NMR spectrum, δ, ppm:
48.0 (C2), 70.4 (C6), 70.5 (C5), 101.8 (C1), 124.4 (C3),
128.6 (C4), 127.1, 128.5, 133.7, 133.9 (Ph), 166.7
(HNC=O). Found, %: C 67.41; H 5.12; N 6.07.
C13H13NO3. Calculated, % : C 67.52; H 5.67; N 6.06.
Therefore oxazoline of high stability was obtained
necessary for the study as a glycosylating reagent.
2-Amino-2,3,4-trideoxy-1,6-anhydro-β-D-eritro-
hex-3-enopyranose (I) was obtained by method [1].
Rf 0.3 (ethyl acetate), [a]D20 –240° (C 1.0, CHCl3).
1H NMR spectrum, δ, ppm: 1.5 br.s (2H, NH2), 2.8 d
(1H, H2, J 3.7 Hz ), 3.64 d.d (1H, H6exo, J 6.4, 4.7 Hz),
3.72 d (1H, H6endo, J 6.4 Hz), 4.58 d.d (1H, H5, J 4.6,
4.4 Hz), 5.35 s (1H, H1), 5.68 d.d (1H, H3, J 9.8, 3.9 Hz),
6.0 d.d (1H, H4, J 9.8, 4.7 Hz). 13C NMR spectrum, δ,
ppm: 51.22 (C2), 70.22 (C6), 70.85 (C5), 104.83 (C1),
128.55 (C3, C4). Found, %: C 56.81; H 7.12; N 11.70.
C6H9NO2. Calculated, %: C 56.68; H 7.13; N 11.02.
(–)-(2S,5R,6R)-6-Acetoxy-5-acetoxyamino-2-
acetoxymethyl-5,6-dihydro-2H-pyran (II). At stirring
and cooling to 0°C to a solution of 0.478 g (3.73 mmol)
of amine I in 20 ml of Ac2O was added a mixture of
0.38 ml of H2SO4 and 18.4 ml of Ac2O. The reaction
mixture was stirred for 39 h at room temperature, then it
was poured into ice water containing 132 g of NaHCO3,
and the mixture was stirred for 2 h at room temperature
and extracted with CHCl3 (5 × 10 ml). Organic solutions
were combined, dried with MgSO4, evaporated, and the
residue was subjected to chromatography. Yield 0.712 g
(89 %). Colorless crystals, mp149–150°C, Rf 0.3 (ethyl
acetate–hexane, 1:1), [a]D20 –16.2° (c 1.0, CH3OH).
1H NMR spectrum, δ, ppm: 1.94 s (3H, CH3), 2.02 s
(3H, CH3), 2.06 s (3H, CH3), 4.08 d.d (1H, CH2, J 11.6,
3.4 Hz), 4.14 d.d (1H, CH2, J 5.3, 11.6 Hz), 4.38 d (1H,
H6, J 2.0, 3.4 Hz), 4.85 m (1H, H3), 5.63 d.t (1H, H4,
J 1.3, 10.4 Hz), 5.76 d.t (1H, H5, J 10.4, 2.0 Hz), 6.10 d
(1H, NH, J 9.1, 4.0 Hz), 6.22 d (1H, H2, J 4.0 Hz).
13C NMR spectrum, δ, ppm: 20.06 (CH3), 20.8 (CH3),
22.9 (CH3), 44.0 (C5), 64.9 (CH2), 68.1 (C2), 89.2 (C6),
125.8 (C3) 126.4 (C4), 169.5 (COOCH3), 170.0
(COOCH3), 170.8 (CONHCH3). Found, %: C 50.81;
H 5.12; N 4.70. C12H17O7N. Calculated, %: C 50.17;
H 5.96; N 4.88.
(–)-(2S,5R,6R)-6-Acetoxy-2-acetoxymethyl-5-
benzoylamino-5,6-dihydro-2H-pyran (V). At stirring
and cooling to 0°C to a solution of 0.1 g (0.43 mmol) of
imide IV in 8 ml of Ac2O was added dropwise a solution
of 0.08 ml of H2SO4 in 3.85 ml of Ac2O. The reaction
mixture was stirred for 39 h at room temperature, then it
was poured into ice water containing 22 g of NaHCO3,
and the mixture was stirred for 2 h at room temperature
and extracted with CHCl3 (5 × 10 ml). Organic solutions
were combined, dried with MgSO4, evaporated, and the
residue was subjected to chromatography. Yield 0.086 g
(60%). Yellow crystals, mp 130–132°C, Rf 0.35 (ethyl
acetate), [a]D20 –56.15° (C 1.0, CHCl3). H NMR
1
spectrum, δ, ppm: 2.02 s (6H, CH3), 4.20 d (2H, CH2,
J 4.6 Hz), 4.68 m (1H, H5), 4.98 m (1H, H2), 6.02 m
(2H, H3, H4), 6.32 d (1H, H6, J 4.0 Hz), 7.45 m (3H, Ph),
7.78 m (1H, Ph), 8.10 m (1H, Ph 13C NMR spectrum, δ,
ppm: 20.07 (CH3), 45.9 (C5), 65.7 (CH2), 71.7 (C2), 92.7
(C6), 125.4 (C4) 128.5 (C3), 127.0, 128.5, 133.6, 133,7
(Ph), 165.1 (CONHPh), 167.1 (COOCH3), 170.7
(COOCH3). Found, %: C 61.81; H 5.19; N 4.01.
C17H19O6N. Calculated, %: C 61.25; H 5.75; N 4.20.
(–)-(1S,3S,6R)-2,9-Dioxa-7-aza-8-phenylbicyclo-
3-acetoxymethyl-[4.3.0]nona-4,7-diene (VI).
A solution of 0.17 ml (0.99 mmol) trimethylsilane triflate
in 3.7 ml of anhydrous dichloroethane was added to
0.242 g (0.9 mmol) of compound V in 5 ml of
dichloroethane. The mixture was stirred at 15°C till the
disappearance of the initial compound (TLC monitoring).
2-Amino-2,3,4-trideoxy-1,6-anhydro-β-D-eritro-
hex-3-enopyranose hydrobromide (III). To a solution
of 0.168 g (1.3 mmol) of amine I in 2 ml of CHCl3 was
added at stirring 0.2 ml (1.3 mmol) of a solution of 46%
HBr in 2 ml CHCl3. In 15 min crystals precipitated. The
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

FAIZULLINA et al.
770
The reaction mixture was passed through a thin bed of
SiO2, the solvent was evaporated, and the residue was
subjected to chromatography. Yield 0.160 g (76%), mp
89–92°C, Rf 0.5 (hexane–ethyl acetate, 1:1), [a]D20 –81.8°
(C 1.0, CHCl3). 1H NMR spectrum, δ, ppm: 2.10 s (3H,
CH3), 4.12 d.d (1H, CH2, J 11.8, 6.1 Hz), 4.25 d.d (1H,
CH2, J 11.8, 3.8 Hz), 4.48 m (1H, H3), 4.62 m (1H, H6),
6.0 d.d (1H, H5, J 10.4, 1.8 Hz), 6.22 m (1H, H4), 6.34 d
(1H, H1, J 7.1 Hz), 7.42 m (3H, Ph), 7.98 m (2H, Ph).
13C NMR spectrum, δ, ppm: 20.8 (CH3), 45.9 (C6), 65.2
(CH2), 66.0 (C3), 101.5 (C1), 126.0 (C5), 127.1, 128.2,
128.4, 128.6 (Ph), 131.8 (C4), 163.9 (–HN=COPh), 170.8
(COOCH3). Found, %: C 65.81; H 5.12; N 5.00.
C15H15O4N. Calculated, %: C 65.92; H 5.53; N 5.13.
column chromatography on silica gel L-40/100 using 30–
100 g per 1 g of substance.
The study was carried out under a financial support of the
Russian Foundation for Basic Research (grant no. 08-03-97033-
p_povolzh’e a) and of the Council for grant of the President of
the Russian Federation (program NSh -1725.2008.3).
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