Crystal structure of methyl 1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronate

Article abstract of DOI:10.1016/S0008-6215(02)00297-5

The identity of the crystalline product formed by the acetylation of a mixture of methyl α- and β-D-glucopyranuronates has been confirmed as being methyl 1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronate (3), which agrees with the assignment from ¹H NMR. The absolute configuration of compound 3 was assigned to agree with the known chirality of the precursor sugar, D-glucono-6,3-lactone.

Full text of DOI:10.1016/S0008-6215(02)00297-5

Carbohydrate Research 337 (2002) 2343–2346
www.elsevier.com/locate/carres
Note
Crystal structure of methyl
1
,2,3,4-tetra-O-acetyl-b- -glucopyranuronate
D
Yuriko Y. Root, Timothy R. Wagner,* Peter Norris*
Department of Chemistry, Youngstown State Uni6ersity, 1 Uni6ersity Plaza, Youngstown, OH 44555-3663, USA
Received 1 April 2002; accepted 31 May 2002
Dedicated to Professor Derek Horton on the occasion of his 70th birthday
Abstract
The identity of the crystalline product formed by the acetylation of a mixture of methyl a- and b-
been confirmed as being methyl 1,2,3,4-tetra-O-acetyl-b- -glucopyranuronate (3), which agrees with the assignment from H
NMR. The absolute configuration of compound 3 was assigned to agree with the known chirality of the precursor sugar,
-glucono-6,3-lactone. © 2002 Elsevier Science Ltd. All rights reserved.
D-glucopyranuronates has
1
D
D
Keywords: Uronate; O-Glycoside; Anomeric configuration; X-Ray analysis; Single-crystal
Acetate esters of carbohydrates serve as useful
derivatives for the study of structure and conformation,
as well as being versatile intermediates in the synthesis
of carbohydrates modified at C-1, the anomeric carbon.
When anomeric mixtures of sugars, either in the fura-
nose or pyranose forms, are acetylated under acidic or
duces a mixture of methyl D-glucopyranuronates, which
are then reacted with acetic anhydride in pyridine to
yield two anomeric acetates, namely methyl 1,2,3,4-
tetra-O-acetyl-a-
D
-glucopyranuronate (2) and methyl
2
1
,2,3,4-tetra-O-acetyl-b- -glucopyranuronate (3). The
D
anomeric acetates are separated by crystallization of the
b anomer 3 from hot 2-propanol to afford compound 3
as needles with melting point 178–180 °C. The two
basic conditions, a mixture of axial (a) and equatorial
1
(
b) products is often produced. H NMR coupling
constants may be used to determine the configuration
at C-1 in common pyranose acetates (apart, for exam-
ple, in the mannopyranose series); however, similar
anomers may be distinguished from coupling constants
1
in their H NMR spectra. For syrupy 2, J
for the
H1ꢀH2
H-1 signal is found to be 3.66 Hz, indicating a gauche
relationship between H-1 and H-2, whereas for crys-
talline 3, JH1ꢀH2 is 7.7 Hz, which usually infers a diaxial
relationship. The crystal structure determination of 3
now confirms the assignment.
1
analysis of furanose acetates is difficult. Determining
the configuration at C-1 is essential to ensure the
stereochemical integrity of the compound in question,
and the application of X-ray diffraction in determining
relative (and when possible absolute) stereochemistry is
very useful.
The single-crystal X-ray crystal structure of 3 (Fig. 1)
4
confirms the expected C conformation of the pyran-
1
As part of a synthesis of glycomimetic compounds
related to bacterial amino sugars, we repeated the
ose ring and the fact that the pyranoses are the thermo-
dynamic products from the opening of lactone 1 with
preparation of glucopyranuronate tetraacetates 2 and 3
2
(
Scheme 1) as previously reported. Treatment of
D-glu-
curono-6,3-lactone (1) with NaOH in methanol pro-
*
Corresponding authors. Tel.: +1-330742-1553; fax: +1-
3
30-742-1579
E-mail address: pnorris@cc.ysu.edu (P. Norris).
Scheme 1.
0
008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00297-5

2
344
Y.Y. Root et al. / Carbohydrate Research 337 (2002) 2343–2346
whereas the endocyclic C-1ꢀO-1 bond is shorter in 3
1.416 A versus 1.426 A). The molecular structure and
(
,
,
numbering scheme for the atoms are shown in Fig. 1.
Fig. 2 shows the packing of the molecules of 3 in the
unit cell, projected along the c-axis. The adjacent layers
of molecules shown along the b-axis are related by the
respective 2-fold screw axis. Intermolecular hydrogen
bonds extend from H(C-5) to O-5, H(C-7) to O-9 and
H(C-13) to O-11 at distances of 2.408, 2.567, and 2.556
A
,
, respectively.
1
. Experimental
General methods.—The melting point was deter-
Fig. 1. Molecular structure of 3, with displacement ellipsoids
at the 50% probability level. Hydrogen atoms drawn as circles
with an arbitrary radius.
mined on a Mel-Temp apparatus and is uncorrected.
1
The H NMR spectrum of 3 was recorded on a Varian
Gemini 2000 instrument at 400 MHz as a solution in
CDCl with Me Si as the internal standard.
3
4
Compound 3 was prepared by treating
D-glucurono-
6
,3-lactone (1) with a methanolic solution of NaOH
and acetylation of the resulting crude product mixture
with acetic anhydride in pyridine as described previ-
2
ously. The b anomer 3 was crystallized from 2-
propanol, and the sample for X-ray analysis was
obtained by recrystallizing the solid twice more from
1
the same solvent. H NMR: l 2.02 (s, 3H, COCH ),
3
2
3
9
.03 (s, 6H, 2×COCH ), 2.10 (s, 3H, COCH ), 3.73 (s,
3
3
H, OCH ), 4.15 (d, J 9.5 Hz, 1H, H-5), 5.11 (dd, J 7.8,
3
.0 Hz, 1H, H-2), 5.20 (dd, J 9.0, 9.5 Hz, 1H, H-4), 5.25
(
dd, J 9.0, 9.0 Hz, 1H, H-3), 5.74 (d, J 7.7 Hz, 1H,
H-1). Evaporation of the mother liquors gave a syrup
1
that was mainly the a-anomer 2 as seen by H NMR
spectroscopy.
Single-crystal X-ray structure of 3.—X-Ray data
were collected at 100 K on a Bruker SMART APEX 4k
CCD Single-Crystal Diffractometer equipped with a
normal focus, 2.4 kW sealed tube X-ray source
Fig. 2. Packing diagram for 3, projected along the c-axis.
Dotted circles O, shaded circles C. Dashed lines represent
intermolecular hydrogen bonds.
(
0
graphite monochromatized MoKa radiation, u=
.71073 A) operating at 50 kV and 40 mA. The diffrac-
,
methoxide. Interestingly in CDCl3 solution the ob-
tion data was obtained by collection of 606 frames at
each of three 8 settings, 0, 120, and 240°, using a scan
width of 0.3° in ꢀ. At the end of the data collection, 50
initial frames were recollected to monitor crystal decay.
The exposure time was 20 s/frame.
1
served H NMR J
of 7.7 Hz for 3 is less than for
H1ꢀH2
the same protons in the related 1,2,3,4,6-penta-O-ace-
-glucopyranose (8.4 Hz) suggesting that replac-
tyl-b-D
ing the CH OAc group in that compound with the
2
CO CH group in 3 alters the conformation of the
2
3
The initial unit cell parameters were determined using
pyranose ring in the latter. The crystal structure of the
4
69 reflections harvested from 900 frames using Bruk-
3
pentaacetate determined by Jones et. al. shows the
4
er’s SMART program. These parameters were then used
to integrate all the data in Bruker’s SAINT program,
pyranose ring to be close to a perfect chair, whereas the
structure of 3 in Fig. 1 clearly shows distortion away
from a perfect chair around the ring, which is compat-
4
where global refinement of the unit cell parameters was
also performed to give the final values utilized in the
subsequent structural analysis. Prior to structure solu-
tion and refinement, the data files written by SAINT
were processed through SADABS5 for correction of er-
rors due to absorption by the glass capillary, crystal
decay, and other effects.
1
ible with the smaller JH1ꢀH2 observed in the H NMR
spectrum of 3. When comparing the acetal CꢀO bond
lengths around the anomeric carbon in the two perac-
etates the exocyclic C-1ꢀO-2 bond is longer in uronate
3
than in the pentaacetate (1.414 A versus 1.408 A),
, ,

Y.Y. Root et al. / Carbohydrate Research 337 (2002) 2343–2346
2345
The structure was solved via direct methods using
Table 2
Fractional atomic coordinates (×10 )
isotropic displacement parameters (A ×10 ) for 3
4
a
6
and equivalent
Bruker’s SHELXS program, and refined via full-matrix
2
3
2
6
least squares against F on all data using SHELXL
.
Structure plots that appear in this paper were obtained
from the program SHELXP. Positions for all non-hy-
b
Atom
x
y
z
U(eq)
6
drogen atoms were refined anisotropically, followed by
isotropic refinement of all hydrogen positions. The
absolute structure could not be determined reliably due
to the absence of significant anomalous scatterers in the
sample, although it was taken to be correct based on
the NMR data. Refinement data are summarized in
O(1)
O(2)
O(3)
O(4)
O(5)
O(6)
O(7)
O(8)
O(9)
O(10)
O(11)
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)
9127(2)
10,883(2)
8566(2)
12,609(2)
15,196(2)
12,638(2)
12,762(2)
9180(2)
10,681(2)
7332(2)
5854(2)
10,163(3)
11,722(3)
11,109(3)
9899(3)
8371(3)
7147(3)
4587(3)
9929(3)
10,851(4)
14,372(3)
15,041(4)
13,337(3)
14,853(3)
9671(3)
10,549(1)
11,221(1)
11,443(1)
9436(1)
10,057(1)
8331(1)
7230(1)
8229(1)
8521(1)
10,789(1)
9419(1)
10,332(1)
9705(2)
8802(2)
9088(2)
9703(1)
10,047(2)
9680(2)
11,731(2)
12,654(2)
9668(2)
9363(2)
7545(2)
7165(2)
8025(2)
7135(2)
902(1)
−32(1)
−856(1)
−265(1)
174(1)
21(1)
24(1)
35(1)
24(1)
34(1)
22(1)
31(1)
22(1)
34(1)
30(1)
27(1)
21(1)
19(1)
20(1)
20(1)
19(1)
21(1)
32(1)
27(1)
39(1)
23(1)
33(1)
22(1)
27(1)
22(1)
28(1)
1231(1)
252(1)
Table
1 and atomic coordinates and equivalent
1915(1)
3043(1)
2249(1)
2019(1)
226(1)
isotropic displacement parameters are listed in
Table 2.
Table 1
452(1)
887(1)
Crystal data summary and refinement results for 3
1561(1)
1243(1)
1890(1)
2628(2)
−579(1)
−767(2)
−340(1)
−1126(2)
857(1)
1328(2)
2675(1)
2957(2)
Structural formula
Formula weight
Color
C H O
20 11
376.31
Colorless
15
Crystal size (mm)
Crystal system
Space group
0.20×0.06×0.04
Orthorhombic
P2 2 2 (No. 19)
1
1 1
a (A
,
)
)
)
7.5120(18)
13.864(3)
16.918(4)
1761.9(7)
4
1.419
0.71073
100(2)
b (A
,
c (A
,
V (A )
,
3
Z
8788(4)
3
zcalc (g/cm )
u(MoK ) (A
Temperature (K)
a
,
)
E.s.d.’s are given in parentheses.
U(eq) is defined as one third of the trace of the orthogo-
a
b
−1
v (mm
)
0.123
nalized U tensor.
ij
q Range for data
collection (°)
1.90–28.37
Limiting indices
−95h59, −185k518,
−
225l521
No. of reflections collected 16136
No. of independent
reflections
No. of parameters
Refinement method
4247 (Rint=0.0643)
Supplementary data
315
Complete structural data has been deposited at the
Cambridge Crystallographic Data Centre, which may
be obtained from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge, CB2 IEZ, UK.
Full-matrix least squares on
2
F
Hydrogen atom positions
Final R indices [I\2|(I)] R (F) =0.0431,
Refined
a
1
2
b
wR (F ) =0.0795
2
a
Final R indices (all data)
R (F) =0.0737,
1
2
b
wR (F ) =0.0881
Acknowledgements
2
2
Goodness-of-fit on F
0.970
Absolute structure
parameter
−0.1(9)
The funds for the CCD X-ray diffractometer at
Youngstown State University were provided by the
National Science Foundation (CCLI-0087210) and the
Ohio Board of Regents Action Fund (Grant CAP-491).
Other funding for this work was provided in part by the
American Chemical Society Petroleum Research Fund
and the University Research Council at Youngstown
State University as part of the PACER initiative.
Largest diff. peak and hole 0.187 and −0.186
−3
(
e A
,
)
a
R (F)=SꢀꢀF ꢀ−ꢀF ꢀꢀ/SꢀF ꢀ with F \4.0|(F).
1
o
c
o
2 2
o
2 2 1/2
o
b
2
2
wR (F )=[S[w(F −F ) ]/S[w(F ) ]] with F \4.0|(F),
2
−
o
c
o
1
2
2
2
2
o
and w =| (F ) +(W·P) +T·P, where P=(Max(F , 0)+
o
2
c
2
F )/3, W=0.0345, and T=0.00.

2
346
Y.Y. Root et al. / Carbohydrate Research 337 (2002) 2343–2346
4
5
6
.
SMART Ver. 5.625. Data Collection and SAINT-Plus Ver.
.22 Data Processing for SMART System, Bruker Analyt-
ical X-Ray Instruments, Madison, WI, USA, 2001.
References
6
1
. Collins, P. M.; Ferrier, R. J. Monosaccharides. Their
Chemistry and Their Roles in Natural Products; John Wiley
and Sons: Chichester, 1995.
. Sheldrick, G. M. SADABS ver. 2.03, Software for Area
Detector Absorptions and Other Corrections, Bruker Ana-
lytical X-Ray Instruments, Madison, WI, USA, 2001.
. Sheldrick, G. M. SHELXTL NT ver. 6.10, Software Package
for the Refinement of Crystal Structures, Bruker
Analytical X-Ray Instruments, Madison, WI, USA,
2000.
2
. Bollenback, G. N.; Long, J. W.; Benjamin, D. G.;
Lindquist, J. A. J. Am. Chem. Soc. 1955, 77, 3310–3315.
. Jones, P. G.; Sheldrick, G. M.; Kirby, J.; Glenn, R. Z.
Kristallogr. 1982, 161, 245–251.
3