Synthesis, characterization, and crystal structure of sodium (methyl α- D -mannopyranosid)uronate monohydrate

Article abstract of DOI:10.1055/s-0033-1340843

TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl)-mediated oxidation of methyl α-d-mannopyranoside with sodium hypochlorite gave sodium (methyl α-d-mannopyranosid)uronate, which was obtained as a crystalline monohydrate in ~70% yield without chromatography. Its purity was proved by NMR spectroscopy, a newly developed HPLC method, combustion analysis, and X-ray crystallography. The crystal structure, solved from synchrotron diffraction data in space group P2₁2₁2₁, revealed that the packing of the uronate molecules is connected by an extensive network of hydrogen bonds, and that the Na⁺ ion is coordinated by six oxygen ligands from one water and three surrounding sugar molecules. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340843

PAPER
▌1073
pSapyenr thesis, Characterization, and Crystal Structure of Sodium
(
Methyl α-D-Mannopyranosid)uronate Monohydrate
Sodium (Methyl α-D-M
a
annopyranosid)uronate Monohydrate
b
a
Peng Xu, Zbigniew Dauter, Pavol Kováč*
a
NIDDK, LBC, National Institutes of Health, Bethesda, MD 20892-0815, USA
Fax +1(301)4805703; E-mail: kpn@helix.nih.gov
b
Macromolecular Crystallography Laboratory, NCI, Argonne National Laboratory, Argonne, IL 60439, USA
Received: 07.01.2014; Accepted after revision: 29.01.2014
cious metal catalyst or protection and deprotection of in-
termediates, and gives the desired product in higher yield.
In addition, the newly developed HPLC method, which al-
lows assessing the presence or absence of salts in product
Abstract: TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl)-mediat-
ed oxidation of methyl α-D-mannopyranoside with sodium hypo-
chlorite gave sodium (methyl α-D-mannopyranosid)uronate, which
was obtained as a crystalline monohydrate in ~70% yield without
chromatography. Its purity was proved by NMR spectroscopy, a 2, may be generally applicable in the uronic acid series.
newly developed HPLC method, combustion analysis, and X-ray
When the TEMPO-promoted oxidation with sodium hy-
crystallography. The crystal structure, solved from synchrotron dif-
pochlorite was applied to 1 (Scheme 1), we initially expe-
rienced difficulties in separating large amount of salts
drogen bonds, and that the Na ion is coordinated by six oxygen li- from the desired product.
fraction data in space group P2 2 2 , revealed that the packing of
1
1 1
the uronate molecules is connected by an extensive network of hy-
+
gands from one water and three surrounding sugar molecules.
Key words: mannuronic acid, oxidation, chemoselective methyla-
tion, TEMPO, HPLC
ONa
HO
HO
HO
OH
O
O
HO
HO
TEMPO, NaOCl (aq), KBr
–3 °C, ~70%
OH
O
0
1
OMe
2
OMe
In connection with other work in this laboratory, a need
arose for a convenient intermediate toward derivatives of
methyl α-D-mannopyranosiduronic acid. As with other
glycosides of hexuronic acids, older preparations of such
Scheme 1 Oxidation of methyl α-D-mannopyranoside (1) with
TEMPO
Previous reports on oxidation of unprotected hexopyrano-
sides in this way lack relevant information regarding the
above, as they describe the isolation of product of oxida-
1
,2
compounds involve multistep synthesis through oxida-
tion of variously protected derivatives of methyl α-D-
mannopyranoside (1). Isolation of products in these situa-
tions is usually straightforward because the desired prod-
uct can be readily isolated from crude reaction mixtures
by extraction into organic solvent and purification by
chromatography. Unprotected glycosides can be oxidized
1
0
11
tion as the corresponding ester, acid, or do not offer
4
,12
sufficient experimental details. Also, assessing the de-
gree of purity (absence of salts) of the sodium uronate dur-
ing various stages of purification was not straightforward
at first because, for obvious reasons, TLC or NMR spec-
troscopy could not be used for this purpose. Since 3 does
not show strong rotary power and decomposes before
melting temperature, these techniques do not provide ad-
equate evidence of purity. TLC on normal-phase silica gel
of a sample of 2 that contained salts showed, after char-
ring, a single compact spot, but purification by preparative
chromatography using the same medium was inconsis-
tent. Eventually, guided by the excellent review by Tojo
3
–5
catalytically (O /Pt) but results vary considerably. In
2
this way, for example, potassium (methyl α-D-mannopy-
ranosid)uronate was obtained in 57.7% yield from 1 but
6
attempts to oxidize phenyl-α- and -β-D-glucosides failed.
Unprotected alkyl glycosides have been selectively oxi-
7
dized at the primary position also with calcium or sodium
hypochlorite in the presence of 2,2,6,6-tetramethylpiperi-
8
dine-1-oxyl (TEMPO), the method being based on the
9
work by Semmelhack and co-workers. Alkali metal salts
8
and Fernandez, we developed a protocol allowing isola-
of uronic acids are important intermediates to alkyl uro-
nates, which are starting points toward more complex de-
rivatives in these series. Here we describe the application
tion of crystalline 3 in good yield (~70%) without chroma-
tography. It involves termination of the oxidation reaction
by addition of HCl to slight acidity, and conversion of ex-
cess of the acid and most of salts present to NaCl, some of
which could be precipitated and filtered off. Pure 3 could
be obtained readily from the filtrate by crystallization (see
experimental section). Purity of the material obtained,
which was confirmed by X-ray and combustion analysis,
could be confidently proved also by a reverse-phase
HPLC method that we have developed (Figure 1). Sam-
ples of 3 containing various amounts of NaCl (e.g., B, C,
or D, Figure 1) are eluted from a C18 column as two
8
of the method for the preparation of sodium (methyl α-D-
mannopyranosid)uronate (2), which is now described and
fully characterized through its crystalline monohydrate 3
for the first time. Compared to protocols toward mannuro-
nate intermediates developed earlier, the advantage of the
one described here lies in that it does not require a pre-
SYNTHESIS 2014, 46, 1073–1078
Advanced online publication: 19.02.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1340843; Art ID: SS-2014-M0005-OP
Georg Thieme Verlag Stuttgart · New York
©

1074
P. Xu et al.
PAPER
peaks, one co-eluting with a sample of NaCl (Figure 1, A)
and the other with material that gave correct combustion
analysis figures for 3 (Figure 1, G). That 3 was a monohy-
drate was confirmed by X-ray analysis. Presence of ~1%
NaCl in 3 can be readily seen by our HPLC analysis (Fig-
ure 1, D). HPLC analysis of the crystalline material isolat-
ed here (two crops, combined yield, ~70%) showed that
the amount of NaCl present was negligible (Figure 1, E
and F), evidence for which was provided by each crop
passing the test of purity by combustion analysis (see ex-
perimental section) as confidently as the recrystallized
material that was subjected to the X-ray crystal structure
analysis.
The overall yield of oxidation could be somewhat in-
creased by chemoselective methylation13 of the material
remaining in the mother liquor after crystallization of 3, to
give the corresponding methyl ester. Methyl (methyl α-D-
mannopyranosid)uronate (4) was previously synthesized
Figure 2 ORTEP plot of the molecule 3 with anisotropic displace-
ment ellipsoids at 50% probability
1
4–17
1
13
Sodium (methyl α-D-mannopyranosid)uronate monohy-
drate (3) crystallized in the space group P2 2 2 with one
and characterized.
Our material produced H and C
1
1 1
NMR data (see experimental section), which agreed with
those found in a not readily accessible source.17
molecule in the asymmetric unit and one accompanying
molecule of water. The crystal structure was solved from
Figure 1 HPLC analysis of products of TEMPO-catalyzed, NaOCl oxidation of methyl α-D-mannopyranoside (1); inset shows expansion of
the relevant region at sensitivity ~5 times increased. A, NaCl; B, 1:1 (w/w) NaCl/3 mixture; C, 1:10 (w/w) NaCl/3 mixture; D, 1:100 (w/w)
NaCl/3 mixture; E, first crop of crystals (59% yield); F, second crop of crystals (recrystallized material obtained from mother liquor after crys-
tallization of the first crop, making the total yield to ~70%); G, analytical sample of 3 that was subjected to X-ray crystal structure analysis; S:
HPLC area count; T: retention time.
Synthesis 2014, 46, 1073–1078
© Georg Thieme Verlag Stuttgart · New York

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Sodium (Methyl α-D-Mannopyranosid)uronate Monohydrate
1075
the diffraction data measured at the synchrotron beam line possessing the mannuronate moiety are available, but the
and refined to R1 = 0.034 and wR2 = 0.125, with other de- bond lengths and angles of the carboxylate ring show typ-
tails available in Table 1. The coordinate uncertainty of ical values, close to those observed in the structures of the
the non-hydrogen atoms is better than 0.002 Å. The se- similar compounds, for example sodium D-glucuronate
1
8
lected geometrical parameters are shown in Table 2. The monohydrate, potassium and rubidium D-glucuronate
1
9
20
molecular structure and atom numbering scheme are pre- dihydrates, D-galacturonic acid monohydrate, and
sented in Figure 2.
2
1
methyl 4-O-methyl-α-D-glucopyranuronate.
4
The sugar moiety adopts a chair C conformation with All hydrogen atoms in the hydroxyl groups and the water
1
axially connected methoxy group at C1 and hydroxyl molecule are engaged in intermolecular hydrogen bonds,
+
group at C2 and equatorially connected two hydroxyl and with the geometry indicated in Table 3. The Na ion is co-
one carboxylate group at C3, C4, and C5, respectively. ordinated in the form of slightly distorted octahedron by
The carboxylate group is symmetric in terms of both C–O O3 and O4 hydroxyl oxygen atoms of one sugar molecule,
bond lengths, but its torsion angle with respect to the py- the ring O5 oxygen and O52 carboxylate oxygen atoms of
ranose ring is twisted to about 90° from the ideal gauche the second molecule, the O53 carboxylate oxygen atom of
conformation. No other crystal structures of compounds the third molecule and a water oxygen atom. The coordi-
Table 1 Diffraction Data and Refinement Statistics
Empirical formula
Formula weight
Beamline
C H NaO
7 13 8
248.16
24-ID-C @ APS
0.61992
Wavelength (Å)
Crystal size (mm)
Temperature (K)
Space group
Cell dimensions
a (Å)
0.10 × 0.15 × 035
100
P2 2 2
1
1
1
6.96
b (Å)
11.79
12.07
990.4
0.19
c (Å)
Volume (Å3)
–
1
Absorption coefficient (mm )
F(000)
544
θmax (°)
31.7
Index ranges
–9 ≤ h ≤ +9, –19 ≤ k ≤ +19, –20 ≤ l ≤ +20
Reflections measured/unique
Data (Friedel mates separate)
Data (Friedel mates separate) [F >4σ (F)]
Restraints
17981/2417
4230
4180
0
Parameters
154
R(int)
0.043
Flack parameter
0.096(59)
0.0337
0.0340
0.1249
CCDC964974
Final R1 factor [F >4σ (F)]
Final R1 factor (all data)
Final wR2 factor (all data)
CSD deposition code
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Georg Thieme Verlag Stuttgart · New York
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P. Xu et al.
PAPER
Table 2 Selected Geometrical Parameters of 3a
Bond
Distance (Å)
1.5243(21)
1.5362(19)
1.5196(17)
1.5398(19)
1.5325(17)
1.4021(16)
1.4248(16)
1.4349(21)
1.4228(16)
1.4174(18)
1.4216(17)
1.4340(16)
1.2593(15)
1.2595(16)
Angle (°)
Bond angle
O5–C1–C2
C1–C2–C3
C2–C3–C4
C3–C4–C5
C4–C5–O5
C5–O5–C1
C1–O1–C11
C5–C51–O52
C5–C51–O53
O52–C51–O53
Angle (°)
C1–C2
112.39(9)
110.74(11)
111.03(10)
110.26(9)
109.05(11)
114.06(10)
112.39(12)
116.81(10)
118.11(10)
124.93(10)
C2–C3
C3–C4
C4–C5
C5–C51
C1–O1
C1–O5
O1–C11
C2–O2
C3–O3
C4–O4
C5–O5
C51–O52
C51–O53
Torsion angle
O5–C1–C2–C3
O5–C1–C2–O2
O5–C1–O1–C11
C2–C1–O5–C5
C1–C2–C3–C4
C1–C2–C3–O3
C2–C3–C4–C5
C2–C3–C4–O4
C3–C4–C5–O5
C3–C4–C5–C51
C4–C5–O5–C1
C4–C5–C51–O52
C4–C5–C51–O53
Torsion angle
Angle (°)
50.92(11)
O1–C1–C2–C3
O1–C1–C2–O2
C2–C1–O1–C11
O1–C1–O5–C5
O2–C2–C3–C4
O2–C2–C3–O3
O3–C3–C4–C5
O3–C3–C4–O4
O4–C4–C5–O5
O4–C4–C5–C51
C51–C5–O5–C1
O5–C5–C51–O52
O5–C5–C51–O53
– 72.74(11)
164.93(8)
–157.90(9)
62.99(13)
70.49(12)
– 50.01(12)
176.74(8)
– 61.12(12)
– 177.39(7)
64.55(10)
178.85(8)
– 29.35(13)
154.98(9)
– 71.41(12)
78.15(12)
– 58.25(12)
– 49.71(11)
–170.21(8)
53.61(12)
175.75(8)
– 57.78(10)
–175.84(8)
60.79(11)
89.04(13)
– 86.63(13)
+
Coordination of Na ion
Bond
Distance (Å)
Bond angle
Angle (°)
69.69(6)
89.04(8)
150.38(4)
126.85(7)
91.29(7)
66.97(6)
143.11(5)
84.12(6)
Bond angle
Angle (°)
Na1–O3′
2.3641(18)
2.4439(20)
2.5105(20)
2.2638(18)
2.5540(24)
2.3017(21)
O3′–Na1–O4′
O3′–Na1–O5
O3′–Na1–O52
O3′–Na1–O53′′
O3′–Na1–W1
O5–Na1–O52
O5–Na1–O53′′
O5–Na1–W1
O4′–Na1–O5
103.87(7)
98.39(8)
84.18(5)
158.93(4)
76.30(5)
102.67(8)
101.23(5)
Na1–O4′
O4′–Na1–O52
O4′–Na1–O53′′
O4′–Na1–W1
O52–Na1–O53′′
O52–Na1–W1
O53–Na1–W1
Na1–O5
Na1–O52
Na1–O53′′
Na1–W1
Symmetry of O3′ and O4′ atoms is 1 + x, y, z and of O53′′ atom is 1/2 + x, 1/2–y, 1–z.
a
The standard uncertainties are shown in parentheses.
Synthesis 2014, 46, 1073–1078
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PAPER
Sodium (Methyl α-D-Mannopyranosid)uronate Monohydrate
1077
nation geometry of sodium ion is shown in Figure 3. Inci- ed at 200 nm. Conversion of crude 2 to the corresponding methyl es-
1
3
ter was performed as described except that Na CO was used as
dentally, analogous atoms of the three sugar and one water
2
3
+
the base. Unless stated otherwise, solutions were concentrated (ro-
tary evaporator) at 40 °C/2 kPa. Combustion analyses were per-
formed by Atlantic Microlab, Inc., Norcross, GA.
molecules coordinate the Na ion in the structure of sodi-
1
8
um D-glucuronate, but in the latter structure the coordi-
nation is much more distorted from the octahedral
geometry. The intermolecular hydrogen bonds and coor-
X-ray Crystal Structure Analysis
A single crystal of 3 was glued at the tip of the thin glass capillary,
mounted at the goniometer head and placed in the stream of 100 K
+
dination of Na by three sugar molecules create three-
dimensional network of strong interactions extending
throughout the whole crystal.
N gas at the goniostat of the NE-CAT beam line 24-ID-C at the Ad-
2
vanced Photon Source, Argonne, USA. The data collection param-
eters are presented in Table 1. Diffraction images were integrated,
reflection intensities scaled and merged with program HKL2000.22
Pairs of reflections related by center of symmetry (Friedel mates)
were kept separate to utilize the potential anomalous diffraction sig-
nal contained in the data. The structure was solved using program
SHELXD and refined by full-matrix least-squares technique using
SHELXL. All non-hydrogen atoms were refined anisotropically
and all hydrogen atoms, identified in the difference electron density
map, were refined isotropically as riding on their parent atoms. The
2
3
2
4
Flack parameter refined to 0.096(59), confirmed the chirality of
the molecule on the basis of weak, but significant amount of anom-
alous signal in diffraction data, despite using short X-ray wave-
length at which the anomalous correction of sodium is
2
5
f′′(Na) = 0.019.
Sodium (Methyl α-D-Mannopyranosid)uronate Monohydrate
(
3)
TEMPO (48 mg, 0.31 mmol, 0.02 equiv) and 0.5 M KBr (3.09 mL,
.54 mmol, 0.1 equiv) were added to a solution of methyl α-D-man-
1
nopyranoside (1; 3.0 g, 15.4 mmol, 1.0 equiv) in H O (20 mL) con-
2
tained in a 200 mL two-necked round-bottomed flask equipped with
a thermometer. While the temperature of the yellow solution
formed was kept between 0–3 °C (ice-salt bath), an aq solution of
NaOCl (made from commercial, household bleach containing
6.15% of NaOCl, 57 mL, 46.3 mmol, 3.0 equiv) was added during
+
Figure 3 Coordination of the Na ion. Distances to neighboring at-
oms are given in Å. O3′ and O4′ atoms belong to molecule trans-
formed by 1 + x, y, z and O53′′ atom to molecule transformed by 1/2
x, 1/2–y, 1–z from the original position.
+
30 min, dropwise with stirring. The stirring of the clear solution was
continued at 0–3 °C for 1 h, when pH was adjusted to 10 by the ad-
dition of aq 1 N NaOH (~20 mL). Additional amount of NaOCl so-
lution was added (19 mL, 15.4 mmol, 1.0 equiv), and the mixture
was stirred for 3 h. TLC (R = 0.5, CH Cl –MeOH, 1:1) showed that
Table 3 Hydrogen Bondsa
D–H
d(D.A.) < DHA
A
Symmetry of A
f
2
2
(
Å)
(°)
all the starting material was consumed and that a slower moving
product was formed. The pH of the solution was adjusted to 5.0 with
aq 1 N HCl (~3.5 mL, portionwise) and then brought to pH 7.0 by
the addition of solid NaHCO (~1.5 g). After washing with CH Cl
O2–HO2
O3–HO3
O4–HO4
W1–HW1
2.786
2.663
2.586
2.894
2.761
162.3
164.1
173.1
125.6
157.0
O53
O4
[–x, ½ + y, 3/2–z]
[–x, ½ + y, 3/2–z]
[–1/2 + x, ½–y, 1–z]
[1/2 – x,1–y, –1/2 + z]
[x, y, z]
3
2
2
(150 mL) to remove TEMPO, the aqueous phase was concentrated.
O53
O1
The residual H O was removed by co-evaporation with absolute
2
EtOH (3 × 200 mL) and drying at r.t. and <133 Pa overnight. MeOH
(150 mL) was added and the mixture was stirred for 20 min, filtered,
and the solids were washed with MeOH until no desired product
could be detected (TLC, eluent: same as above) in the filtrate (~6
times). The filtrates were combined and concentrated to give 6.3 g
of solid crude product. Pure 3 (colorless crystals, 2.25 g, 59%, Fig-
W1–HW2
O2
a
d(D.A.) is the donor–acceptor distance and < DHA is the donor–hy-
drogen–acceptor angle.
ure 1, E) was obtained by crystallization from H O and drying at
2
60 °C and <133 Pa overnight. For crystallization, the crude product
(
6.3 g) was dissolved in warm (~60 °C) H O (30 mL) and the solu-
2
Methyl α-D-mannopyranoside (1) was purchased from Sigma
Chemical Co. and used as supplied. Optical rotations were mea-
tion was concentrated slowly at 60 °C/13 kPa. Shortly after the first
crystals appeared, the flask was removed from the evaporator, and
crystallization was completed at r.t. with occasional manual stirring.
After ~30 min, the crystals were filtered, washed with cold (~0 to
sured at r.t. for solution in H O with a digital Jasco automatic polar-
2
imeter, Model P-2000. Melting points were measured on a Kofler
hot stage. TLC was performed on silica gel 60 coated glass slides.
Visualization of spots was effected by charring with 5% H SO in
+5 °C) 20% H
O in MeOH (3 × 2 mL) and sucked dry; mp 267–269
2
°C (dec.); [α]
+48.5 (c 1, H O).
2
4
D
2
1
EtOH. NMR spectra were recorded at 600 MHz ( H) and 150 MHz
C) with a Bruker Avance spectrometer. Assignments of NMR
Anal. Calcd for C H NaO ·H O: C, 33.88; H, 5.28. Found: C,
7
11
7
2
1
3
(
33.77; H, 5.25.
signals were made by homonuclear and heteronuclear 2-dimension-
al correlation spectroscopy, run with the software supplied with the
spectrometers. HPLC was performed with Agilent 1100 Series
Chromatography System, using a 4.6 × 250 mm SunFire column
packed with C-18 silica gel, particle size, 5 μm (Waters). A mobile
For recrystallization to obtain the analytical sample (Figure 1, G),
the amounts of H O and 80% MeOH for washing were adjusted ac-
2
cordingly.
1
H NMR (600 MHz, D O): δ = 4.79 (d, J = 2.0 Hz, 1 H, H-1), 3.90
2
phase of 100% H O (1 mL/min) was used. Compounds were detect-
(dd, J = 2.0, 3.0 Hz, 1 H, H-2), 3.87 (d, J = 9.0 Hz, 1 H, H-5), 3.80
2
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1073–1078

1078
P. Xu et al.
PAPER
(
3
dd, J = 9.0, 9.3 Hz, 1 H, H-4), 3.77 (dd, J = 3.0, 9.3 Hz, 1 H, H-3),
.41 (s, 3 H, 1-OCH3).
(4) Melvin, F.; McNeill, A.; Henderson, P. J. F.; Herbert, R. B.
Tetrahedron Lett. 1999, 40, 1201.
1
3
(5) Li, K.; Helm, R. F. Carbohydr. Res. 1995, 273, 249.
C NMR (150 MHz, D O): δ = 177.5 (C-6), 101.6 (C-1), 73.6 (C-
2
(6) Marsh, C. A. J. Chem. Soc. 1952, 1578.
5
), 71.0 (C-3), 70.5 (C-2), 69.5 (C-4), 55.6 (1-OCH3).
(
7) McDonald, C. E.; Nice, L. E.; Shaw, A. W.; Nestor, N. B.
Tetrahedron Lett. 1993, 34, 2741.
+
HRMS-ESI: m/z [M + H] calcd for C H NaO : 231.0475; found:
2
7
12
7
31.0477.
(
8) Tojo, G.; Fernandez, M. I. TEMPO-mediated oxidations, In
Oxidation of Primary Alcohols to Carboxylic acids. A Guide
to Common Practice; Tojo, G.; Fernandez, M. I., Eds.;
Springer Verlag: Berlin, 2007, 79–103.
Anal. Calcd for C H NaO ·H O: C, 33.88; H, 5.28. Found: C,
3
7
11
7
2
4.01; H, 5.12.
Crystallization in the same manner of the material which remained
in the mother liquor gave a second crop of crystals (1.0 g), which
showed the presence of small amount of salts (HPLC profile not
shown in Figure 1). Recrystallization from H O gave, after drying,
additional pure 3 (Figure 1, F, 0.38 g, 10%; total yield ~70%).
(9) Semmelhack, M. F.; Chou, C. S.; Cortes, D. A. J. Am. Chem.
Soc. 1983, 105, 4492.
(
10) Becher, J.; Seidel, I.; Plass, W.; Klemm, D. Tetrahedron
2
2
006, 62, 5675.
(
(
11) Baisch, G.; Öhrlein, R. Carbohydr. Res. 1998, 312, 61.
12) Ciriminna, R.; Blum, J.; Avnir, D.; Pagliaro, M. Chem.
Commun. 2000, 1441.
(13) Walvoort, M. T. C.; Sail, D.; van der Marel, G. A.; Codée, J.
D. C. Synthesis of Methyl Glycuronates by Chemo- and
Regioselective TEMPO/BAIB-Oxidation, In Carbohydrate
Chemistry: Proven Synthetic Methods; Vol. 1; Kováč, P.,
Ed.; CRC/Taylor and Francis: Boca Raton, 2011, 99–105.
Anal. Calcd for C H NaO ·H O: C, 33.88; H, 5.28. Found: C,
7
11
7
2
3
4.04; H, 5.32.
Variable amount of methyl (methyl α-D-mannopyranosid)uronate
4), corresponding to 5–10% of the desired product of oxidation,
was obtained as a syrup by methylation (with MeI and Na CO in
(
2
3
DMF) of the material from the combined mother liquors.
1
H NMR (600 MHz, D O): δ = 4.83 (d, J = 2.3 Hz, 1 H, H-1), 4.20
d, J = 9.3 Hz, 1 H, H-5), 3.94 (dd, J = 2.3, 3.0 Hz, 1 H, H-2), 3.90
t, J = 9.3 Hz, 1 H, H-4), 3.82 (s, 3 H, 6-OCH ), 3.81 (dd, J = 3.0,
.3 Hz, 1 H, H-3), 3.43 (s, 3 H, 1-OCH3).
2
(
14) Edington, R. A.; Hirst, E. L.; Percival, E. E. J. Chem. Soc.
(
(
9
1
955, 2281.
3
(
(
15) Schmidt, H. W. H. Tetrahedron Lett. 1967, 235.
16) Evtushenko, E. V.; Ovodov, Y. S. Khim. Prir. Soed. (Engl.
Transl.) 1987, 23, 166; Chem. Abstr. 1988, 108, 112869.
17) Betaneli, V. I.; Brikhanova, O. V.; Ott, A. J.; Kochetkov, N.
K. Bioorg. Khim. 1990, 16, 390; Chem. Abstr. 1990, 113,
152911.
13
C NMR (150 MHz, D O): δ = 172.3 (C-6), 102.0 (C-1), 72.4 (C-
2
5
), 70.7 (C-3), 70.0 (C-2), 68.7 (C-4), 56.0 (1-OCH ), 53.6 (6-
3
(
(
OCH3).
+
HRMS-ESI: m/z [M + Na] calcd for C H NaO : 245.0637; found:
2
8
14
7
45.0633.
18) DeLucas, L. J.; Gartland, G. L.; Bgg, C. E. Carbohydr. Res.
1
978, 62, 213.
(
(
19) Gurr, G. E. Acta Crystallogr. 1963, 16, 690.
20) Tang, H.-R.; Belton, P. S.; Dvies, S. C.; Hughes, D. L.
Carbohydr. Res. 2001, 330, 391.
Acknowledgment
This research was supported by the Intramural Research Program of
the NIH, NCI, and NIDDK.
(
(
21) Hirsch, J.; Langer, V.; Koos, M. Molecules 2005, 10, 251.
22) Otwinowski, Z.; Minor, W. Methods Enzymol. 1997, 276,
3
07.
Supporting Information for this article is available online at
(23) Sheldrick, G. M. Acta Crystallogr., Sect. D 2008, 64, 112.
(24) Flack, H. D. Acta Crystallogr., Sect. A 1983, 39, 876.
http://www.thieme-connect.com/ejournals/toc/synthesis. SnuIoipgfmr tooatrin guSIopi
n
nfo itrmart
(
25) The structural data have been deposited at the Cambridge
Crystallographic Data Centre with the ID code CCDC
964974. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via
References
(1) Ault, R. G.; Haworth, W. N.; Hirst, E. L. J. Chem. Soc. 1935,
www.ccdc.cam.ac.uk/data_request/cif or by writing to the
Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; fax: +44(1223)336033; E-mail:
deposit@ccdc.cam.ac.uk.
5
17.
(
(
2) Stacey, M.; Wilson, P. I. J. Chem. Soc. 1944, 587.
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Synthesis 2014, 46, 1073–1078
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