Novel autoxidation and Michael addition of a butenolide-containing sugar leading to a C-branched-chain glucopyranosidulose, and X-ray structure of intermediates

Article abstract of DOI:10.1016/S0008-6215(03)00257-X

A butenolide-containing sugar available from the aldol condensation of methyl 4,6-O-benzylidene-α-D-glucopyranosid-2-ulose with diethyl malonate is autoxidized at the C-3 position into the corresponding α,β-unsaturated γ-lactone sugar by air, which subsequently undergoes 1,4-conjugate (Michael) addition of hydroxide ion (or water) leading to a C-branched-chain glucopyranosidulose. The autoxidations are also performed in weakly basic, neutral and weakly acidic medium, respectively.

Full text of DOI:10.1016/S0008-6215(03)00257-X

Carbohydrate Research 338 (2003) 1737ꢀ1743
/
www.elsevier.com/locate/carres
Novel autoxidation and Michael addition of a butenolide-containing
sugar leading to a C-branched-chain glucopyranosidulose, and X-ray
structure of intermediates
Hong-Min Liu,* Fuyi Zhang, Jianye Zhang, Shi Li
Department of Chemistry, Zhengzhou University, Daxue Road, Zhengzhou 450052, PR China
Received 18 February 2003; accepted 28 May 2003
Abstract
A butenolide-containing sugar available from the aldol condensation of methyl 4,6-O-benzylidene-a-
D-glucopyranosid-2-ulose
with diethyl malonate is autoxidized at the C-3 position into the corresponding a,b-unsaturated g-lactone sugar by air, which
subsequently undergoes 1,4-conjugate (Michael) addition of hydroxide ion (or water) leading to a C-branched-chain
glucopyranosidulose. The autoxidations are also performed in weakly basic, neutral and weakly acidic medium, respectively.
# 2003 Elsevier Ltd. All rights reserved.
Keywords: Butenolide-containing sugar; 2-Oxoglucopyranoside; Autoxidation
1. Introduction
2-C-branched-chain and a carbonyl group at the C-3
position. These types of functionalities could be very
useful for the construction of five- and six-membered
carbocyclic ring carbohydrates by an intermolecular
Claisen condensation and a Robinson annulation.
As a continuation of our studies, in this paper we
report on the mechanism of this transformation by
presenting evidence of autoxidation, followed by Mi-
chael addition, and report on the synthesis of two
butenolide-containing intermediates. Butenolide-con-
taining compounds are of interest as they are considered
to be potential anticancer agents, cycooxygenase inhi-
bitors, and phospholipase A2 inhibitors, etc.12ꢀ16
Since C-branched-chain glycopyranosiduloses are very
efficient chiral building blocks for the synthesis of
biologically active substances containing carbocyclic
ring systems,1ꢀ3 synthesis of such types of structural
units has gained importance in recent years. Although
the stereoselective addition of a nucleophile to a
glycosidulose is an efficient method for synthesis of C-
branched-chain sugars, previous studies on their synth-
eses were focused on the use of fully protected sugars,4,5
because partially protected and unprotected glycosidu-
loses are very difficult to synthesize selectively, and are
unstable.6ꢀ9 A C-branched-chain sugar has never been
synthesized from a partially protected or unprotected ‘2-
oxoglycoside,’ except for that which we reported on the
synthesis of indole derivatives,10 as well as a one-step
synthesis of a 2-C-branched-chain glycopyranosid-3-
ulose (2) (Scheme 1), by the reaction of ‘2-oxoglucopyr-
anoside’ (1) with diethyl malonate.11 We were intrigued
by the reaction mechanism, as well as by the structural
features of 2, which contains an active methylene at the
2. Results and discussion
The reaction of compound 18 with diethyl malonate in
the presence of sodium methoxide for 3.5ꢀ4 h affords
/
the 2-C-branched-chain sugar 2. Reaction monitoring at
different time intervals enabled the trapping of the
reaction intermediates and gave evidence for the me-
chanism. Compound 1 in chloroform was added drop-
wise to a stirred solution of diethyl malonate and
sodium methoxide in methanol, and stirring was con-
tinued for 30 min at 0 8C. The reaction was neutralized
* Corresponding author. Tel./fax: ꢁ86-371-7767200.
/
E-mail address: liuhm@zzu.edu.cn (H.-M. Liu).
0008-6215/03/$ - see front matter # 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0008-6215(03)00257-X

1738
H.-M. Liu et al. / Carbohydrate Research 338 (2003) 1737ꢀ1743
/
intermediate 5, generated from 3 by hydrogen abstrac-
tion, permits extensive delocalization of the unpaired
electron into a five-membered ring conjugate system. It
remains reactive toward oxygen to produce peroxy
radical 6, which then abstracts hydrogen from 3 or
other substances to generate the hydroperoxy butenolide
derivative 7. This hydroperoxide is then reduced,
resulting in the formation of 4.
Further experiments were performed to investigate
the autoxidation of 3 followed by Michael addition.
Compound 3 or a mixture of 3 and 4 as starting material
was treated under the same conditions as described
above, resulting in the formation of 2 in both cases. In
addition, we found that 3 can be autoxidized in weakly
basic, neutral, and weakly acidic medium, even without
added air. Table 1 depicts the results. In the presence of
water, 2-C-branched-chain sugar 2 were obtained (en-
Scheme 1. Stereoselective synthesis of 2-C-branched-chain
glycopyranosid-3-ulose 2 from 1.
with acetic acid, and the butenolide-containing sugar 3
(Scheme 2) was isolated in 68% yield in another
experiment. Alternatively, the mixture was stirred for
30 min, and then heated at 25ꢀ28 8C for 1 h while
/
simultaneously bubbling air into the mixture. This
mixture was then quenched with acetic acid to give a
mixture of 3 and the corresponding oxidation inter-
mediate product 4, which was recrystallized from
methanol to give mixed crystals in a ratio of about
2:3. Its 1H NMR spectrum and X-ray structure are
shown in Figs. 1 and 2, respectively. The mixed crystal
was chromatographed on silica gel, affording 3 and 4,
respectively. Compound 4 was recrystallized from
ethanol and acetone also to give a single crystal. Fig. 3
shows an ORTEP of its structure. However, when the
silica gel was eluted with chloroform, 2 was obtained
besides compound 3 and a small amount of 4, indicating
that 4 can be transformed into 2 in weakly acidic
medium. When the reaction was continued for about
2.5 h, and a small amount of water was added, 2 was
eventually obtained as the sole product.
tries 1ꢀ3). This is because 4, which is formed in basic
/
solution, was then subjected to Michael addition by
hydroxide ion or water. Under anhydrous conditions,
the terminal products were 4 (entries 4ꢀ6). Except for
/
the hydroxide ion, oxygen nucleophiles such as alkoxide
ions and carboxylate anions cannot effectively attack on
4 to generate the corresponding C-branched-chain
sugars.
The intermediates 316 and 4 and the mixed crystal of 3
and 4 were all characterized by spectroscopic data and
X-ray crystallographic analysis. The high-resolution
mass spectrum of compound 3 displayed an [Mꢁ1]
/
Obviously, the reactants undergo an aldol condensa-
tion, with subsequent autoxidation, followed by 1,4-
conjugate (Michael) addition as the three main steps in
one pot, as described in Scheme 2. The reaction
sequence starts with a base-catalyzed aldol condensation
between ‘2-oxoglucopyranoside’ 1 and diethyl malonate
to form the five-membered ring butenolide-containing
intermediate 3, in which case, ester exchange and
intramolecular cyclization are involved. This is followed
by autoxidation of 3 at the C-3 position to give 4. Both 3
and 4 bear a,b-unsaturated g-lactone structures, which
are considered as potentially biologically active
compounds.12ꢀ15 1,4-Conjugate (Michael) addition of
hydroxide ion to the a,b-unsaturated g-lactone sugar
(4), followed by decarboxylation, eventually generates 2.
In this procedure, 3 can be easily autoxidized into 4,
perhaps due to the fact that its five-membered lactone is
peak at m/z 363.1065, indicating the formula to be
C18H18O8. 13C NMR signals at d 165.7 and 160.2, and
absorptions at 1808 and 1735 cmꢂ1 in the IR spectrum
were assigned to carbonyl groups of the lactone and
COOMe groups, respectively. In the 1H NMR spectrum,
the proton that appeared as a singlet at d 6.15 was
assigned to H-1. The proton at d 5.25 (d, Jꢃ
/
10.0 Hz)
was coupled with that at d 4.08 (t, Jꢃ
/
10.0 Hz). They
were ascribed to H-3 and H-4. The 13C NMR peak at d
94.6 was assigned to C-1. The two signals at d 77.5 and
61.7 were ascribed to C-3 and C-4, respectively. The
newly formed CÄ/C exhibited two peaks at d 166.6 (C-2)
and d 118.3. All the assignments were made on the basis
of 2D NMR spectra. The X-ray analysis of 4 showed
that crystalline structure has molecular stacking along a
one-dimensional chain. Fig. 4 depicts the interaction
among the molecules. In each parallel stacking, they are
assembled in polymers through intermolecular hydrogen
bonds between O-5 of one molecule and 3-OH of the
˚
very planar, with an r.m.s deviation of 0.0091 A among
the five atoms.16 A possible mechanism for the auto-
xidation of 3 is as shown in Scheme 3. The radical
Scheme 2. A possible pathway for the formation of 2.

H.-M. Liu et al. / Carbohydrate Research 338 (2003) 1737ꢀ
/
1743
1739
Fig. 1. 1H NMR spectrum of the mixed crystal for 3 and 4 isolated in a ratio of ꢀ
2:3.
/
Fig. 2. X-ray crystal structure of the mixed crystal for 3 and 4 isolated in a ratio of about 2:3.
˚
next one. The distance of 3-OHÁ Á ÁO-5 is 2.858 A and the
recorded on a Shimadzu IR-435 instrument using KBr
disks in the 400ꢀ
4000 cmꢂ1 region. NMR spectra were
taken in CDCl3 with Me4Si as the internal standard on a
Bruker DPX-400 spectrometer, and the chemical shifts
are given in d values. Liquid secondary-ion mass
spectrometry spectra were taken with a ZAB-2SE
double-focusing mass spectrometer (VG Analytical,
angle of 3-OHÁ Á ÁO-5 is 138.438.
/
3. Experimental
3.1. General methods
Manchester, UK). Methyl 4,6-O-benzylidene-a-
D-glu-
copyranosid-2-ulose was prepared as we reported pre-
viously.8 Dry CHCl3 was prepared by refluxing it with
CaH2. All organic solutions from workups were dried
over anhyd sodium sulfate.
TLC was performed on precoated plates of silica gel 60
F254. Components were detected by UV light. Melting
points were determined on a WC-1 melting-point
apparatus and are uncorrected. Infrared spectra were
3.2. Methyl (2R,4aR,6S,9aR,9bS)-4,4a,6,8,9a,9b-
hexahydro-6-methoxy-8-oxo-2-
phenylfuro[2?,3?:4,5]pyrano[3,2-d]-1,3-dioxin-7-
carboxylate (3)
Diethyl malonate (1.2 mL, 7.4 mmol) was added
dropwise to a solution of Na (0.60 g, 26.1 mmol) in
anhyd MeOH (20 mL) at 0 8C with stirring. After 10
min, a solution of methyl 4,6-O-benzylidene-a-
D-gluco-
pyranosid-2-ulose (1, 0.40 g, 1.43 mmol) in 20 mL of dry
CHCl3 was added. The mixture was stirred for another
30 min, made neutral with 50% HOAc, and evaporated.
The residue was dissolved in water, extracted with
EtOAc, then dried. The solvent was evaporated, and
the residue was crystallized from MeOH to afford the
title compound 3 (0.35 g, 68%), which was recrystallized
Fig. 3. X-ray crystal structure of intermediate 4.

1740
H.-M. Liu et al. / Carbohydrate Research 338 (2003) 1737ꢀ1743
/
Scheme 3. A possible mechanism for the autoxidation of 3.
from MeOHꢀ
172 8C; IR (KBr): 1808 (lactone CÄ
965, 748, and 699 cmꢂ1 (Ph); 1H NMR (400 MHz,
CDCl3): d 3.57 (s, 3 H, OMe), 3.62ꢀ3.69 (m, 1 H, H-5),
3.79 (t, 1 H, J 10.0 Hz, H-6a), 3.93 (s, 3 H, COOCH3),
4.08 (t, 1 H, J 10.0 Hz, H-4), 4.41 (dd, 1 H, J 4.8, 10.0
Hz, H-6b), 5.25 (d, 1 H, J 10.0 Hz, H-3), 5.56 (s, 1 H,
/
acetone as colourless crystals: mp 170ꢀ
/
(Mꢂ1); Anal. Calcd for C18H18O8 (362.33): C, 59.67; H,
5.01. Found: C, 59.76; H, 5.10.
/
/
O), 1735 (CÄO),
/
/
3.3. Methyl (2R,4aR,6S,9aR,9bS)-4,4a,6,8,9a,9b-
hexahydro-9a-hydroxy-6-methoxy-8-oxo-2-
phenylfuro[2?,3?:4,5]pyrano[3,2-d]-1,3-dioxin-7-
carboxylate (4)
ArÃ
7.49ꢀ
CDCl3) d 52.8 (COOMe), 55.9 (OMe), 61.7 (C-4), 68.4
(C-6), 77.5 (C-3), 84.3 (C-5), 94.6 (C-1), 101.6 (ArÃC),
118.3 (ÄCÇ), 126.1, 128.3, 129.3, 136.3 (Ar), 160.2
(COOMe), 165.7 (lactone CO), 166.6 (C-2); HRLSIMS:
Calcd for C18H19O8, m/z 363.1080 (Mꢁ1), C18H17O8 m/
z 361.0923 (Mꢂ1). Found, 363.1062 (Mꢁ1), 361.0951
/
CH), 6.15 (s, 1 H, H-1), 7.37ꢀ
/
7.41 (m, 3 H, ArÃ
/
H),
/
7.51 (m, 2 H, ArÃ
/
H); 13C NMR (100 MHz,
3.3.1. Method 1. As for the procedure described above,
after the mixture was stirred for another 30 min, instead
/
of neutralization, it was heated at 25ꢀ28 8C while
/
/
simultaneously bubbling air into the mixture. One
hour later, the mixture was treated as described above
to afford white powder, which was recrystallized from
MeOH to give colourless crystals suitable for X-ray
crystallograhpic analysis. The 1H NMR spectrum of the
colourless crystals were taken in CDCl3, which is shown
in Fig. 1. The mixed crystals were chromatographed on
/
/
/
silica gel with petroleum etherꢀ
afford the title compound 4 (0.23 g, 42%) (4:1).
Compound 4 was recrystallized from ethanolꢀacetone
to afford colourless crystals, also suitable for X-ray
crystallograhpic analysis: mp 208ꢀ210 8C; IR (KBr):
3446 (OH), 1791 (lactone CÄO), 1728 (ester CÄO), 753,
and 707 cmꢂ1 (Ph); H NMR (400 MHz, CDCl3): d
3.59 (s, 3 H, OMe), 3.78ꢀ3.85 (m, 2 H, H-4, H-6), 3.94
(s, 3 H, COOMe), 4.32 (dt, 1 H, Jꢃ4.8, 10.0 Hz, H-5),
4.44 (dd, 1 H, J 4.8, 10.0 Hz, H-6a), 5.69 (s, 1 H, ArÃ
CH), 6.16 (s, 1 H, H-1), 7.38-7.40 (m, 3 H, ArÃH), 7.49ꢀ
7.51 (m, 2 H, ArÃ
H); 13C NMR (100 MHz, CDCl3) d
53.0 (COOMe), 56.6 (OMe), 61.5 (C-4), 68.5 (C-6), 82.9
(C-5), 95.2 (C-1), 99.4 (C-3), 101.7 (ArÃC), 121.6 (Ä
CÇ), 126.2, 128.4, 129.4, 136.0 (Ar), 160.0 (COOMe),
160.8 (lactone CÄO), 164.0 (C-2); HRLSIMS: Calcd for
/
acetone as eluent to
/
/
/
/
1
/
/
/
/
/
/
/
/
Fig. 4. Perspective ORTEP view of molecules of intermediate 4,
exhibiting the intermolecular hydrogen bonds. Hydrogen
omitted.
/
Table 1
Autoxidation of 3 into 4 under various conditions
Entry Reagents
Time (h) Temperature (8C) Product (yield) (%)
1
2
3
4
5
6
Butenolide-containing intermediate 3, NaOCH3, MeOH, moist air
3 and 4, NaOCH3, MeOH, moist air
3, NaHCO3, H2O, THF
˚
3, H2NNHCSNH2, NH4Cl, CHCl3, MeOH, 4 A sieves
˚
3, p-Anisidine, NH4Cl, CHCl3, 4 A sieves
3
25ꢀ
/
28
2 (47)
2 (50)
2 (55)
4 (55)
4 (54)
4 (64)
3
25ꢀ
/
28
21
1
rt
50
1.5
70
55ꢀ
/
60
˚
3, NBS, DMF, 4 A sieves
rt

H.-M. Liu et al. / Carbohydrate Research 338 (2003) 1737ꢀ
/
1743
1741
C18H19O9, m/z 379.1029 (Mꢁ
377.0873 (Mꢂ1). Found, 379.1052 (Mꢁ
(Mꢂ1); Anal. Calcd for C18H18O8 (378.33): C, 57.14; H,
/
1), C18H17O9 m/z
Table 2
Summary of crystallographic data for the mixed crystal of 3
and 4 in a ratio of 2:3, and 4
/
/
1), 377.0877
/
4.80. Found: C, 57.01; H, 4.75.
The mixed crystal of 3
and 4 in a ratio of 2:3,
and 4
3.3.2. Method 2. A mixture of 3 (0.30 g, 0.83 mmol),
˚
NH4Cl (0.030 g, 0.56 mmol), 4 A molecular sieves (5 g),
Chemical formula C18H17.63O8.63
Formula weight 371.95
C18H18O9
378.32
18
and dry CHCl3 (20 mL) was heated at 50 8C with
stirring, to which H2NNHCSNH2 (0.075 g, 0.82 mmol)
in anhyd MeOH (12 mL) was added. After 1 h, the
molecular sieves were removed. The mixture was
evaporated, dissolved in EtOAc, then washed twice
with water, dried and evaporated. Some ethanol was
added, and the residue was crystallized to afford the title
compound 4 (0.17 g, 55%), identical in all respects with
the sample obtained as described above.
Temperature (8C) 18
Wavelength (Mo 0.71073
0.71073
˚
Ka, A)
Crystal system
Space group
Unit cell dimen-
sions
Orthorhombic
P212121
Orthorhombic
P212121
˚
a (A)
6.2914(13)
11.579(2)
23.725(5)
1728.3(6)
4
6.3659(13)
11.591(2)
23.782(5)
1754.8(6)
4
˚
b (A)
˚
c (A)
3.3.3. Method 3. A mixture of 3 (0.21 g, 0.58 mmol), p-
anisidine (0.071 g, 0.58 mmol), NH4Cl (0.020 g, 0.37
˚
mmol), 4 A molecular sieves (4 g), and dry CHCl3 (20
3
V (A )
˚
Z
Dcalc (mg mꢂ3
)
1.429
0.115
779
1.432
0.116
792
mL) was heated at 55ꢀ
the molecular sieves were removed. The solution was
washed with water (2ꢄ4 mL), dried, and evaporated.
/
60 8C with stirring for 1.5 h, then
m (mmꢂ1
F(000)
)
/
Crystal size (mm3) 0.30ꢄ
/
0.20ꢄ
/
0.20
0.30ꢄ
/
0.20ꢄ0.20
/
The residue was treated as described in Method 2 to give
the title compound 4 (0.12 g, 54%), identical in all
respects with the sample obtained as described above.
Diffractometer
Rigaku RAXIS-IV
Rigaku RAXIS-
IV
u Range for data 1.72ꢀ
/25.00
1.71ꢀ27.53
/
collection (8)
Index ranges
3.3.4. Method 4. A solution of 3 (0.21 g, 0.58 mmol),
NBS (0.10 g, 0.56 mmol) and 0.8 mL of anhyd DMF
ꢂ
/
75
135
275
2574/2060
R(int)ꢃ0.0738
/
h 5
k 5
l 527
/
7,
ꢂ
/
85
155
305
5999/3520
R(int)ꢃ0.0412
Direct method
SHELX-97)
/
h 5
k 5
l 530
/
8,
ꢂ
/
/
/
0,
ꢂ
/
/
/
0,
ꢂ
/
/
/
ꢂ
/
/
/
was stirred at room temperature (rt) (17ꢀ20 8C) for 70 h,
/
Reflections
then EtOAc (7 mL) was added. The solution was treated
as described in Method 3 to give the title compound 4
(0.14 g, 64%), identical in all respects with the sample
obtained as described above.
collected/unique
/
/
Structure solution Direct method
(
Refinement meth- full-matrix least-
SHELX-97)
(
full-matrix least-
squares on F2
3520/0/244
od
squares on F2
2060/0/249
3.4. Methyl 4,6-O-benzylidene-2-C-
methoxycarbonylmethyl-a-D-ribo-hexopyranosid-3-ulose
(2)
Data/restraints/
parameters
Final R indices
R1ꢃ
wR2ꢃ
1.137
/
0.0851,
R1ꢃ
wR2ꢃ
1.021
/0.0557,
[I ꢁ
/
2s(I)]
/0.1916
/
0.1064
Goodness-of-fit
on F2
3.4.1. Method 1. Na (0.30 g, 13.0 mmol) was dissolved
in MeOH (18 mL), to which 3 (0.30 g, 0.83 mmol) in
CHCl3 (15 mL) was added. The mixture was stirred at
25ꢀ28 8C and moist air was bubbled through. The
/
solvent was added at regular intervals to supplement
the loss of its evaporation by air. After 3 h, the mixture
was neutralised with 50% HOAc and evaporated. The
residue was dissolved in water, extracted with EtOAc,
and dried. The solvent was evaporated, and the residue
was crystallized from MeOH to give 2 (0.14 g, 47%),
identical in all respects with the sample we reported.11
solution, then dried. The solvent was evaporated to
give the titled compound 2 as a white powder (0.16 g,
55%), identical in all respects with the sample obtained
as described above.
3.5. X-ray diffraction experiment
3.4.2. Method 2. 3 (0.30 g, 0.83 mmol) was dissolved in
THF (8 mL), to which NaHCO3 (catalytic amount) and
water (0.4 mL) was added. The mixture was stirred at rt
Crystal data and experimental details for the mixed
crystal of 3 and 4 in ratio of 2:3, and the crystal 4 are
contained in Table 2. All measurements were made on a
(17ꢀ
/
20 8C) for 21 h, then evaporated. The residue was
Rigaku RAXIS-IV imaging plate with graphite mono-
˚
chromated Mo Ka radiation (lꢃ0.71073 A). Ortho-
dissolved in EtOAc, washed twice with satd NaCl
/

1742
H.-M. Liu et al. / Carbohydrate Research 338 (2003) 1737ꢀ1743
/
Table 3
Fractional atomic coordinates and equivalent isotropic displacement factors for the mixed crystal of 3 and 4 in a ratio of 2:3, and 4
2
103)
˚
Atom
x
y
z
Ueq (A ꢄ
/
The mixed crystal of 3 and 4 in a ratio of 2:3
O(3)
O(4)
O(5)
O(6)
O(2)
O(1)
O(7)
O(8)
O(9)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
ꢂ
/
1769(5)
6700(3)
8202(3)
10727(3)
12654(3)
9019(3)
9229(3)
12374(3)
13438(3)
9327(5)
9798(4)
10475(4)
9828(4)
8979(4)
8277(4)
7405(4)
7352(4)
6593(4)
5511(4)
4891(5)
5315(5)
6384(5)
7011(4)
11791(4)
11613(4)
12510(4)
14348(5)
8759(7)
1707(1)
1660(1)
1311(1)
1352(2)
879(1)
45(1)
35(1)
43(1)
59(1)
37(1)
48(1)
63(1)
56(1)
47(2)
31(1)
31(1)
35(1)
30(1)
32(1)
44(1)
40(1)
36(1)
42(1)
51(2)
49(1)
51(2)
42(1)
37(1)
35(1)
41(1)
73(2)
97(3)
697(4)
1423(5)
1392(6)
ꢂ
/
4105(5)
2497(6)
3869(6)
2736(6)
ꢂ
/
ꢂ3(1)
/
ꢂ
/
195(2)
916(1)
ꢂ/
1573(9)
653(2)
ꢂ
/
3302(6)
460(2)
729(2)
ꢂ
/
1518(7)
196(7)
1029(2)
1437(2)
1107(2)
1499(2)
2013(2)
2237(2)
2012(2)
2203(2)
2623(2)
2858(2)
2662(2)
1183(2)
817(2)
ꢂ
/
813(7)
2462(7)
3455(8)
304(8)
ꢂ
/
ꢂ
/
ꢂ/
1449(7)
1911(8)
3624(8)
4915(9)
4444(8)
2754(8)
596(7)
ꢂ
/
1286(7)
2795(8)
4215(11)
4006(11)
ꢂ
/
603(2)
752(3)
ꢂ
/
ꢂ/
ꢂ
/
361(3)
Crystal 4
O(1)
O(2)
7481(4)
3673(4)
3613(4)
4249(3)
9037(3)
6697(3)
8799(4)
7749(4)
3404(4)
8268(5)
6483(5)
4760(5)
5782(5)
7403(4)
8379(5)
9043(8)
6288(5)
7755(5)
9248(7)
5244(5)
3503(5)
2227(6)
533(6)
5759(2)
2320(2)
4258(2)
6782(2)
5980(2)
8298(2)
2629(2)
1562(2)
5677(2)
5189(2)
4520(2)
5152(2)
6008(2)
6713(2)
7595(2)
6204(4)
3394(2)
2489(2)
667(3)
ꢂ
/
2(1)
50(1)
63(1)
47(1)
37(1)
40(1)
49(1)
74(1)
64(1)
65(1)
40(1)
34(1)
35(1)
33(1)
36(1)
49(1)
98(2)
40(1)
46(1)
82(1)
42(1)
40(1)
48(1)
55(1)
54(1)
52(1)
45(1)
45(1)
1361(1)
1327(1)
1663(1)
892(1)
O(3)
O(4)
O(5)
O(6)
1713(1)
184(1)
920(1)
O(7)
O(8)
O(9)
C(1)
656(1)
469(1)
731(1)
C(2)
C(3)
1040(1)
1438(1)
1110(1)
1503(1)
C(4)
C(5)
C(6)
C(7)
C(8)
ꢂ355(2)
/
819(1)
604(1)
757(2)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
7642(3)
8399(2)
7980(2)
8597(3)
9675(3)
10104(3)
9480(2)
3191(2)
2023(1)
2242(1)
2668(1)
2857(1)
2628(1)
2213(1)
2020(1)
1190(1)
92(6)
1368(6)
3076(5)
4429(5)
Ueq is defined as one-third of the trace of the orthogonalized Uij tensor.

H.-M. Liu et al. / Carbohydrate Research 338 (2003) 1737ꢀ
/
1743
1743
rhombic mixed crystal of 3 and 4 (0.30ꢄ
/
0.20ꢄ
/
0.20
0.20 mm)
this work. We thank Dr Yagami (Division of Medical
Devices, NIHS) for the MS measurements.
mm) and single crystal of 4 (0.30ꢄ0.20ꢄ
/
/
were selected and mounted on a glass fiber. All data
were collected at a temperature of 291(2) K and
corrected for Lorentz-polarization effects. A correction
for secondary extinction was applied.
References
3.6. Structure solution and refinement
1. Wood, A. J.; Jenkins, P. R.; Fawcett, J.; Russell, D. R. J.
Chem. Soc. Chem. Commun. 1995, 1567ꢀ
2. Wood, A. J.; Holt, D. J.; Dominguez, M.-C.; Jenkins, P.
R. J. Org. Chem. 1998, 63, 8522ꢀ8529.
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2000, 65, 482ꢀ493.
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501.
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1568.
The two structures were solved by direct methods and
expanded using the Fourier technique. The non-hydro-
gen atoms were refined with anisotropic thermal para-
meters. Hydrogen atoms were included but not refined.
The final cycle of full-matrix least-squares refinement
was based on 2060 reflections and 249 variable para-
meters for the mixed crystal of 3 and 4, and 3520
reflections and 244 variable parameters for 4. All
calculations were performed using the SHELX-97 crystal-
lographic software package.17
/
/
/
/
/
/
The final fractional atomic coordinates and equiva-
lent isotropic thermal displacement factors are listed in
Table 3.
8. Liu, H.-M.; Tsuda, Y. Chem. Pharm. Bull. 1996, 44, 80ꢀ
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87.
9. Liu, H.-M.; Tsuda, Y. Chem. Pharm. Bull. 1996, 44, 88ꢀ
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90.
10. Liu, H.-M.; Xu, W.; Liu, Z.-Z. Carbohydr. Res. 2001, 331,
4. Supplementary material
229ꢀ
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334, 323ꢀ326.
12. Lee, G.C.M. Eur. Pat. Appl. EP. 372, 940 1990; Chem.
Abstr. 1990, 113, 191137j.
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232.
The crystal structure data have been deposited with the
Cambridge Crystallographic Data Centre. These data
may be obtained upon request from The Directory,
Cambridge Crystallographic Data Centre, 12 Union
/
13. Brima, T.S. U.S. Patent 4, 968, 817, 1990; Chem. Abstr.
1991, 114, 185246y.
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http://www.csdc.cam.ac.uk. Deposition numbers CCDC
200167 and CCDC 200166.
14. Lee, G.C.M.; Garst, M.E. PCT Int. Appl. WO 91 16, 055,
1991; Chem. Abstr. 1992, 116, 59197m.
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Appl. WO 95 00 501, 1995; Chem. Abstr. 1996, 124,
55954y.
Acknowledgements
16. Zhang, F.; Du, C.-X.; Liu, H.-M.; Zhu, Y. Acta Crystal-
We are grateful to NNSF of P.R. China (No. 20272054)
and HNNSF (No. 0111030300) for financial support of
logr. Sect. C 2001, 57, 1361ꢀ
17. Sheldrick, G. M. SHELXS-97; Gottingen: Germany, 1997.
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1362.
¨