Content uploaded by Robert A Field
Author content
All content in this area was uploaded by Robert A Field
Content may be subject to copyright.
Peracetylated a-D-glucopyranosyl
fluoride and peracetylated a-maltosyl
fluoride
Simone Dedola,
a
David L. Hughes
b
* and Robert A. Field
a
a
Department of Biological Chemistry, John Innes Centre, Colney Lane, Norwich
NR4 7UH, England, and
b
School of Chemistry, University of East Anglia, Norwich
NR4 7TJ, England
Correspondence e-mail: d.l.hughes@uea.ac.uk
Received 23 November 2009
Accepted 29 January 2010
Online 3 February 2010
The X-ray analyses of 2,3,4,6-tetra-O-acetyl--d-glucopyran-
osyl fluoride, C
14
H
19
FO
9
, (I), and the corresponding maltose
derivative 2,3,4,6-tetra-O-acetyl--d-glucopyranosyl-(1!4)-
2,3,6-tri-O-acetyl--d-glucopyranosyl fluoride, C
26
H
35
FO
17
,
(II), are reported. These add to the series of published
-glycosyl halide structures; those of the peracetylated
-glucosyl chloride [James & Hall (1969). Acta Cryst. A25,
S196] and bromide [Takai, Watanabe, Hayashi & Watanabe
(1976). Bull. Fac. Eng. Hokkaido Univ. 79, 101–109] have been
reported already. In our structures, which have been
determined at 140 K, the glycopyranosyl ring appears in a
regular
4
C
1
chair conformation with all the substituents, except
for the anomeric fluoride (which adopts an axial orientation),
in equatorial positions. The observed bond lengths are
consistent with a strong anomeric effect, viz. the C1—O5
(carbohydrate numbering) bond lengths are 1.381 (2) and
1.381 (3) A
˚in (I) and (II), respectively, both significantly
shorter than the C5—O5 bond lengths, viz. 1.448 (2) A
˚in (I)
and 1.444 (3) A
˚in (II).
Comment
Glycosyl fluorides are widely used in carbohydrate chemistry
and biochemistry. The F atom is comparable in size with a
hydroxy group, hence the steric demand upon introduction of
this group is quite small (O’Hagan 2008; Howard et al., 1996).
The popularity of glycosyl fluorides in chemical synthesis is
due to their remarkable stability yet ease of chemospecific
activation in performing glycosylation reactions. One notable
advantage in using glycosyl fluorides as glycosyl donor is their
high thermal stability compared with glycosyl chlorides,
bromides or iodides. The utilization of carbohydrate fluorides
as glycosyl donors originates from the work by Mukaiyama et
al. (1981) on the synthesis of simple glucosides and disac-
charides. Progress made in the utilization of glycosyl fluorides
as donors in the synthesis of O-andC-glycosides has been
reported by Toshima (2000) and updated in the more recent
review by Carmona et al. (2008). Interest in glycosyl fluorides
has increased since Hayashi et al. (1984) developed a reliable
and safe method for the preparation of these compounds by
exposing suitably protected sugars to a 50–70% mixture of
hydrogen fluoride in pyridine. The stability of glycosyl fluor-
ides in their deprotected form also makes them important
compounds for use as mechanistic probes in the elucidation of
enzyme mechanisms and as reagents for enzymatic synthesis
(reviewed by Williams & Withers, 2000). Extending our
interest in the impact of fluorine substitution on carbohydrate
biotransformations (Errey et al., 2009) and the generation of
amylose mimetics (Marmuse et al., 2005; Nepogodiev et al.,
2007; Cle
´et al., 2008), we had cause to investigate glucosyl
fluorides. In this paper, we report the crystal structures of the
2,3,4,6-tetra-O-acetyl--d-glucopyranosyl fluoride, (I), and the
corresponding maltose derivative 2,3,4,6-tetra-O-acetyl--d-
glucopyranosyl-(1!4)-2,3,6-tri-O-acetyl--d-glucopyranosyl
fluoride, (II). The crystal structures obtained integrate with
the published series of -glycosyl halide derivatives; X-ray
structures of peracetylated -glucosyl chloride (James & Hall,
1969) and bromide (Takai et al., 1976) have been reported
previously and the members of this series show most clearly
the anomeric effect, where the preference for the axial
orientation of the halogen atom renders synthesis of the
equatorial counterpart a synthetic challenge. Results from
X-ray analyses typically allow direct evaluation of the impact
of the anomeric effect on sugar structure.
The glucosyl unit in (I) (Fig. 1) adopts a
4
C
1
chair confor-
mation. All bond lengths and angles conform with the values
found in acetylated glucose. Values for the bond lengths which
are affected by the anomeric effect, together with results from
the X-ray crystal structures of other acetylated glucosyl
halides, are summarized in Table 1. The conformational
properties of pyranosyl halides have been explored by a
number of theoretical studies using model compounds such as
2-fluorotetrahydropyran or 2-chlorotetrahydropyran. The
theoretical approaches to generate three-dimensional struc-
tures rely on experimental data to generate the necessary set
of parameters. In this context, good agreement was obtained
by Tvaroska & Carver (1994) by comparison of their theore-
tical results with experimental ones obtained for the acetyl
and benzoyl d-xylopyranose fluorides. To our knowledge, no
crystal structure of anomeric aldohexosyl fluorides has been
reported to date. The structural data reported herein are in
agreement with the theoretical data obtained by Tvaroska &
Carver (1994), supporting the theoretical methodology
reported in their study.
Influences on the bond lengths in a series of X-ray crystal
structures of glycopyranosides have been examined by Briggs
organic compounds
o124 #2010 International Union of Crystallography doi:10.1107/S0108270110003641 Acta Cryst. (2010). C66, o124–o127
Acta Crystallographica Section C
Crystal Structure
Communications
ISSN 0108-2701
et al. (1984). They concluded that there is no correlation
between the electronegativity of the substituent at the
anomeric position and the C5—O5 bond length. Comparison
of C5—O5 bond lengths in the series of halo-derivatives given
in Table 1 shows a similar lack of correlation. The C1—O5
bonds in the fluoro- and chloroglucosides have similar values
[1.381 (2) A
˚in the fluoride, (I), 1.383 A
˚in the chloride and
1.381 (3) A
˚in the maltosyl fluoride, (II)]; the same bond is
shorter in the glucosyl bromide (1.346 A
˚). Comparing the
sugar-ring bond lengths in these halides with those in penta-
acetyl--d-glucopyranose (Jones et al., 1982), it seems that the
shortening of the C1—O5 bond is accompanied by a propor-
tional lengthening of the C1—C2 and C3—C4 bonds. In
contrast, the C2—C3, C4—C5 and C5—O5 bond lengths
change little, with no apparent correlation with the C1—O5
bond lengths.
In the maltosyl fluoride structure, (II), both pyranose rings
adopt a
4
C
1
chair conformation (Fig. 2). It is interesting to
observe in (II) the orientation of the contiguous pyranose
rings, which is described by the torsion angles around the
glycosidic bonds, C4—O4 and O4—C41, denoted as confor-
mational angles and [in (II), = H4—C4—O4—C41 =
29and = C4—O4—C41—H41 = 32], and by the
valence angle = C4—O4—C41, which is 116.66 (14)in (II).
All these values are in good agreement with those in
-maltoseoctaacetate (Brisse et al., 1982) and -octapropanoate
(Johnson et al., 2007) and conform closely with those in other
maltose derivatives discussed by Johnson et al. (2007) in
respect of having short chains containing an -(1!4) inter-
sugar glycosidic linkage, and are therefore useful as models to
study starch structure. The twist of the nonreducing sugar ring
is defined by the virtual torsion angle O44—C44C41—O4;
this has a value of 4.8 (3)in compound (II), which, if
inserted in an amylose chain of starch (see, for example,
Takahashi & Nishikawa, 2003), would add to the bias of
successive residues, forming a left-handed helix (French &
Johnson, 2007).
Intermolecular interactions in crystals of both (I) and (II)
are principally through weak hydrogen bonds. In (I), there are
five contacts (four C—HO and one C—HF) in which the
HF/O distance is less than 2.55 A
˚. In (II), there are six
interactions (five C—HO and one C—HF). In all these
contacts, the angles subtended at the H atoms (in calculated
sites) are greater than 137and most are greater than 150.
Experimental
The title compounds, (I) and (II), were both obtained as single -
anomers (as judged by
1
H NMR spectroscopy). They were prepared
following known procedures (Juennemann et al., 1993), exposing the
peracetylated glucose or maltose to a 70% mixture of hydrogen
fluoride in pyridine in a Teflon bottle. The resulting products were
purified by crystallization from a mixture of ethyl acetate and hexane
(ratio ca 4:1). Crystals suitable for X-ray diffraction were obtained as
colourless blocks in both cases by slow recrystallization from the
same solvent system.
Compound (I)
Crystal data
C
14
H
19
FO
9
M
r
= 350.29
Monoclinic, P21
a= 5.35502 (11) A
˚
b= 7.96182 (14) A
˚
c= 20.1151 (5) A
˚
= 92.061 (2)
V= 857.06 (3) A
˚
3
Z=2
Mo Kradiation
= 0.12 mm
1
T= 140 K
0.55 0.31 0.11 mm
organic compounds
Acta Cryst. (2010). C66, o124–o127 Dedola et al. C
14
H
19
FO
9
and C
26
H
35
FO
17
o125
Figure 2
The molecular structure of the fully acetylated maltosyl fluoride, (II),
showing the atom-numbering scheme. Displacement ellipsoids are drawn
at the 50% probability level and H atoms are shown as white rods.
Figure 1
The molecular structure of the fully acetylated glucosyl fluoride, (I),
showing the atom-numbering scheme. Displacement ellipsoids are drawn
at the 50% probability level and H atoms are shown as white rods. The
methyl groups of three of the acetyl groups were refined as disordered in
two distinct orientations; only one arrangement for each is shown here.
Data collection
Oxford Xcalibur 3 CCD area-
detector diffractometer
Absorption correction: multi-scan
(CrysAlis RED; Oxford
Diffraction, 2008)
T
min
= 0.970, T
max
= 1.033
24426 measured reflections
2677 independent reflections
2325 reflections with I>2(I)
R
int
= 0.037
Refinement
R[F
2
>2(F
2
)] = 0.033
wR(F
2
) = 0.073
S= 1.02
2677 reflections
224 parameters
1 restraint
H-atom parameters constrained
max
= 0.22 e A
˚
3
min
=0.14 e A
˚
3
Compound (II)
Crystal data
C
26
H
35
FO
17
M
r
= 638.54
Monoclinic, P21
a= 5.63832 (9) A
˚
b= 18.2908 (3) A
˚
c= 14.8144 (2) A
˚
= 94.4966 (15)
V= 1523.09 (4) A
˚
3
Z=2
Mo Kradiation
= 0.12 mm
1
T= 140 K
0.42 0.37 0.14 mm
Data collection
Oxford Xcalibur 3 CCD area-
detector diffractometer
Absorption correction: multi-scan
(CrysAlis RED; Oxford
Diffraction, 2008)
T
min
= 0.923, T
max
= 1.070
40401 measured reflections
4545 independent reflections
3785 reflections with I>2(I)
R
int
= 0.052
Refinement
R[F
2
>2(F
2
)] = 0.048
wR(F
2
) = 0.117
S= 1.07
4545 reflections
404 parameters
1 restraint
H-atom parameters constrained
max
= 0.70 e A
˚
3
min
=0.46 e A
˚
3
Since the anomalous scattering does not allow definitive deter-
mination of the absolute configurations in either of these compounds,
the intensities of Friedel pairs were merged (using the MERG 3
command in SHELXL97; Sheldrick, 2008). The configurations were
already established since these compounds were prepared from -d-
glucose and -d-maltose.
All H atoms were included in idealized positions, with C—H =
0.96–0.98 A
˚and U
iso
(H)=1.5U
eq
(C) for methyl groups or 1.2U
eq
(C)
otherwise. The methyl groups were refined as rigid groups rotating
about the C—Me bond. In compound (I), three of the methyl groups
showed disorder over alternative orientations, all of which were
included as idealized methyl groups with two positions rotated by 60
from each other. These were allowed to rotate about the C—Me
bond, and the site-occupation factors of the two orientations refined
to 0.25 (3):0.75 (3), 0.39 (2):0.61 (2) and 0.22 (2):0.78 (2) for the H
atoms at C22, C42 and C62, respectively.
For both compounds, data collection: CrysAlis CCD (Oxford
Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffrac-
tion, 2008); data reduction: CrysAlis RED; program(s) used to solve
structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine
structure: SHELXL97 (Sheldrick, 2008); molecular graphics:
ORTEPII (Johnson, 1976) and ORTEP-3 (Farrugia, 1997); software
used to prepare material for publication: SHELXL97.
This study was supported by the BBSRC.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: JZ3170). Services for accessing these data are
described at the back of the journal.
References
Briggs, A. J., Glenn, R., Jones, P. G., Kirby, A. J. & Ramaswamy, P. (1984).
J. Am. Chem. Soc. 106, 6200–6206.
Brisse, F., Marchessault, R. H., Pe
´rez, S. & Zugenmaier, P. (1982). J. Am.
Chem. Soc. 104, 7470–7476.
Carmona, A. T., Moreno-Vargas, A. J. & Robina, I. (2008). Curr. Org. Synth. 5,
33–60.
Cle
´, C., Gunning, A. P., Syson, K., Bowater, L., Field, R. A. & Bornemann, S.
(2008). J. Am. Chem. Soc. 130, 15234–15235.
Errey, J. C., Mann, M. C., Fairhurst, S. A., Hill, L., McNeil, M. R., Naismith,
J. H., Percy, J. M., Whitfield, C. & Field, R. A. (2009). Org. Biomol. Chem. 7,
1009–1016.
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.
French, A. D. & Johnson, G. P. (2007). Carbohydr. Res. 342, 1223–1237.
Hayashi, M., Hashimoto, S. & Noyori, R. (1984). Chem. Lett. 10, 1747–1750.
Howard, J. A. K., Hoy, V. J., O’Hagan, D. & Smith, G. T. (1996). Tetrahedron,
52, 12613–12622.
organic compounds
o126 Dedola et al. C
14
H
19
FO
9
and C
26
H
35
FO
17
Acta Cryst. (2010). C66, o124–o127
Table 1
Selected bond lengths (A
˚), including those affected by the anomeric effect, in glycosyl halide derivatives and pentaacetyl--d-gluopyranose.
.
XRC5—O5 O5—C1 C1—XC1—C2 C2—C3 C3—C4 C4—C5
Br
a
Ac 1.458 (14) 1.347 (15) 2.002
f
1.572 (16)
g
1.531 (16)
g
1.600 (16)
g
1.500 (16)
g
Cl
b
Ac 1.445
f
1.383
f
1.777
f
F
c
Ac 1.4477 (18) 1.381 (2) 1.3981 (19) 1.514 (3) 1.512 (2) 1.515 (2) 1.516 (2)
F
d
(Ac)
4
Glc 1.444 (3) 1.381 (3) 1.393 (3) 1.513 (4) 1.527 (4) 1.532 (3) 1.529 (4)
OGly
d
(Ac)
4
Glc 1.433 (3) 1.420 (3) 1.409 (3) 1.514 (4) 1.517 (4) 1.514 (3) 1.532 (4)
OAc
e
Ac 1.422 (4) 1.403 (4) 1.431 (4) 1.507 (4) 1.524 (4) 1.504 (4) 1.534 (4)
Notes: (a) Takai et al. (1976); (b) James & Hall (1969); (c) this work, compound (I); (d) this work, compound (II); (e) Jones et al. (1982); (f) s.u. values are not available; (g) s.u. values are
taken from a mean value.
James, M. & Hall, D. (1969). Acta Cryst. A25, S196.
Johnson, C. K. (1976). ORTEPII. Report ORNL-5138. Oak Ridge National
Laboratory, Tennessee, USA.
Johnson, G. P., Stevens, E. D. & French, A. D. (2007). Carbohydr. Res. 342,
1210–1222.
Jones, P. G., Sheldrick, G. M., Kirby, A. J. & Glenn, R. (1982). Z. Kristallogr.
161, 237–243.
Juennemann, J., Thiem, J. & Pedersen, C. (1993). Carbohydr. Res. 249,
91–94.
Marmuse, L., Nepogodiev, S. A. & Field, R. A. (2005). Org. Biomol. Chem. 3,
2225–2227.
Mukaiyama, T., Murai, Y. & Shoda, S. I. (1981). Chem. Lett. 3, 431–432.
Nepogodiev, S. A., Dedola, S., Marmuse, L., de Oliveira, M. T. & Field, R. A.
(2007). Carbohydr. Res. 342, 529–540.
O’Hagan, D. (2008). Chem. Soc. Rev. 37, 308–319.
Oxford Diffraction (2008). CrysAlis CCD and CrysAlis RED. Versions
1.171.32.24. Oxford Diffraction, Yarnton, Oxfordshire, England.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Takahashi, Y. & Nishikawa, S. (2003). Macromolecules,36, 8656–8661.
Takai, M., Watanabe, H., Hayashi, J. & Watanabe, S. (1976). Bull. Fac. Eng.
Hokkaido Univ. 79, 101–109.
Toshima, K. (2000). Carbohydr. Res. 327, 15–26.
Tvaroska, I. & Carver, J. C. (1994). J. Phys. Chem. 98, 6452–6458.
Williams, S. J. & Withers, S. G. (2000). Carbohydr. Res. 327, 27–46.
organic compounds
Acta Cryst. (2010). C66, o124–o127 Dedola et al. C
14
H
19
FO
9
and C
26
H
35
FO
17
o127
