2,3:4,6-Di-O-isopropyl-idene - L-sorbofuran-ose and 2,3-O-isopropyl-idene - L-sorbofuran-ose

Article abstract of DOI:10.1107/S0108270109008294

In the title compounds, C12H20O6, (I), and C9H16O6, (II), the five-membered furan-ose ring adopts a ⁴ T 3 conformation and the five-membered 1,3-dioxolane ring adopts an E 3 conformation. The six-membered 1,3-dioxane ring in (I) adopts an almost ideal ^O C 3 conformation. The hydrogen-bonding patterns for these compounds differ substanti-ally: (I) features just one intra-molecular O - H...O hydrogen bond [O...O = 2.933 (3) A], whereas (II) exhibits, apart from the corresponding intra-molecular O - H...O hydrogen bond [O...O = 2.7638 (13) A], two inter-molecular bonds of this type [O...O = 2.7708 (13) and 2.7730 (12) A]. This study illustrates both the similarity between the con-formations of furan-ose, 1,3-dioxolane and 1,3-di-oxane rings in analogous isopropyl-idene-substituted carbohydrate structures and the only negligible influence of the presence of a 1,3-dioxane ring on the conformations of furan-ose and 1,3-dioxolane rings. In addition, in comparison with reported analogs, replacement of the -CH2OH group at the C1-furan-ose position by another group can considerably affect the conformation of the 1,3-dioxolane ring.

Full text of DOI:10.1107/S0108270109008294

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
prepared (I) from l-sorbose using acetone as an isopropyl-
idenation agent and concentrated sulfuric acid as a catalyst.
Subsequent selective acid hydrolysis of the 4,6-O-isopropyl-
idene group in (I) afforded the monoisopropylidene-substi-
tuted compound (II).
ISSN 0108-2701
2,3:4,6-Di-O-isopropylidene-a-L-
sorbofuranose and 2,3-O-isopropyl-
idene-a-L-sorbofuranose
a
b
ˇb
´
Vratislav Langer, * Bohumil Steiner and Miroslav Koos *
aEnvironmental Inorganic Chemistry, Department of Chemical and Biological
Engineering, Chalmers University of Technology, SE-412 96 Goteborg, Sweden, and
¨
bInstitute of Chemistry, Centre of Excellence GLYCOMED, Slovak Academy of
´
´
Sciences, Dubravska cesta 9, SK-845 38 Bratislava, Slovakia
Correspondence e-mail: langer@chalmers.se, chemmiro@savba.sk
Received 26 February 2009
Accepted 6 March 2009
Online 14 March 2009
The molecular structures of (I) and (II) are illustrated in
Figs. 1 and 2, respectively [the numbering of atoms corre-
sponds to the numbering according to the IUPAC Nomen-
clature of Carbohydrates (McNaught, 1996)]. The puckering
In the title compounds, C12H20O6, (I), and C9H16O6, (II), the
4
five-membered furanose ring adopts a T3 conformation and
the five-membered 1,3-dioxolane ring adopts an E3 conforma-
tion. The six-membered 1,3-dioxane ring in (I) adopts
an almost ideal OC3 conformation. The hydrogen-bonding
patterns for these compounds differ substantially: (I) features
just one intramolecular O—Hꢀ ꢀ ꢀO hydrogen bond [Oꢀ ꢀ ꢀO =
˚
parameters (Cremer & Pople, 1975) Q = 0.250 (2) A and ’ =
112.2 (6)ꢁ, and the relevant torsion angles (see Table 3) are
indicative of an E3 (EO3) conformation for the O2/C2/C3/O3/
C7 five-membered 1,3-dioxolane ring in (I). Considering the
values for (I) of the relevant torsion angles (Table 3) anꢁd the
˚
2.933 (3) A], whereas (II) exhibits, apart from the corre-
sponding intramolecular O—Hꢀ ꢀ ꢀO hydrogen bond [Oꢀ ꢀ ꢀO =
˚
puckering parameters Q = 0.370 (3) A and ’ = 127.0 (4) , the
˚
4
five-membered O5/C2–C5 furanose ring adopts a T3 (C5TC4)
2.7638 (13) A], two intermolecular bonds of this type [Oꢀ ꢀ ꢀO =
˚
2.7708 (13) and 2.7730 (12) A]. This study illustrates both the
similarity between the conformations of furanose, 1,3-
dioxolane and 1,3-dioxane rings in analogous isopropyl-
idene-substituted carbohydrate structures and the only
negligible influence of the presence of a 1,3-dioxane ring on
the conformations of furanose and 1,3-dioxolane rings. In
addition, in comparison with reported analogs, replacement of
the –CH2OH group at the C1-furanose position by another
group can considerably affect the conformation of the 1,3-
dioxolane ring.
Comment
The title isopropylidene derivatives of l-sorbofuranose,
namely 2,3:4,6-di-O-isopropylidene-ꢀ-l-sorbofuranose, (I),
and 2,3-O-isopropylidene-ꢀ-l-sorbofuranose, (II), are useful
intermediates in organic synthesis. They have been used as
starting materials for the stepwise synthesis of 1-deoxy-
nojirimycin (Beaupere et al., 1989), the 6,6-difluoro analog
(Szarek et al., 1997) and N-butyl-1-deoxynojirimycin (N-Bu
DNJ, Zavesca1) (Boucheron et al., 2005; Godin et al., 2002),
known as a very efficient glycosidase inhibitor used, inter alia,
as a therapeutic agent in the treatment of lysosomal disease. In
the context of studies on the synthesis of imino-sugar deri-
vatives related to nojirimycin and mannojirimycin, we have
Figure 1
A view of (I), showing the atom-numbering scheme. Displacement
ellipsoids are shown at the 50% probability level and H atoms are shown
as small spheres of arbitrary radii. The intramolecular O—Hꢀ ꢀ ꢀO
hydrogen bond is shown as a dashed line.
Acta Cryst. (2009). C65, o151–o154
doi:10.1107/S0108270109008294
# 2009 International Union of Crystallography o151

organic compounds
Figure 4
Figure 2
The hydrogen bonding in (II) depicted as dashed lines. H atoms not
involved in the strong hydrogen bonds have been omitted for clarity.
Symmetry codes and geometric details are listed in Table 2.
A view of (II), showing the atom-numbering scheme. Displacement
ellipsoids are shown at the 50% probability level and H atoms are shown
as small spheres of arbitrary radii. The intramolecular O—Hꢀ ꢀ ꢀO
hydrogen bond is shown as a dashed line.
Related structures include 1-phthalimido-1-deoxy-2,3:4,6-di-
O-isopropylidene-ꢀ-l-sorbofuranose (refcode PHISOR; Glass
& Johnson, 1976), cis-6-(2-deoxy-3,5-O-isopropylidene-1,2-
isopropylidenedioxy-ꢂ-l-xylo-furanosyl)-2,3-dimethyl-1,2,5-
oxadiazinane (refcode XAKKUP; Gravestock et al., 2000) and
[2R,3S,4S,5S,5(2S,3S,4R,5S)]-5-(2,3,4-trihydroxy-5-hydroxy-
methyl-2,3:4,50-di-O-isopropylidene-2-tetrahydrofuranyl)-4-
methyl-2-phenyltetrahydrofuran-3-carbaldehyde (refcode
TEZHAI; Kollmann et al., 2007) which have the exocyclic
–CH2OH group replaced by a more complicated organic
functionality and, finally, (2,3-O-isopropylidene-ꢀ-l-sorbo-
furanose)trimethylplatinum(IV) tetrafluoroborate (refcode
GOZJEK; Junicke et al., 1999) which is a metal–carbohydrate
complex where 2,3-O-isopropylidene-ꢀ-l-sorbofuranose re-
presents a tridentate ligand coordinated to the PtIV centre via
the hydroxyl groups at the C1, C4 and C6 positions.
Figure 3
A projection of (I) (red in the online version of the paper) and (II) (blue)
with the furanose ring fitted as a common fragment. H atoms have been
omitted for clarity.
A comparison of (I) and (II) with these structures shows
only small differences in the conformation of the furanose
4
ring. Only TEZHAI exhibits the E (C4 furanose atom in an
endo direction) conformation, while the 4T3 conformation was
observed for the other structures. Conformational similarity
can also be seen for the 1,3-dioxane ring in (I) and in related
structures. Thus, in (I), PHISOR, TEZHAI and DIPKGA, the
OC3 conformation is slightly distorted to the E5 direction,
while a slight shift in the 4H5 direction is observed for
XAKKUP. Regarding the 1,3-dioxolane ring, its conformation
is considerably affected by the substitution at the C1 furanose
position (–CH2OH versus another substituent). In this respect,
the 1,3-dioxolane ring in (I), (II) and GOZJEK adopts the E3
(O3 atom in an endo direction) conformation, while other
conformations observed are 4T3 (for TEZHAI and
XAKKUP), 3E (for DIPKGA) and 4T3 shifted halfway to the
4E direction (for PHISOR).
conformation, with atom C4 lying in the exo and C5 the endo
direction with respect to the O5/C2/C3 reference plane. Based
on the values of relevant torsion angles (Table 3)ꢁand the
˚
puckering parameters Q = 0.509 (3) A, ’ = 300.0 (19) and ꢁ =
8.7 (3)ꢁ, the O4/C4–C6/O6/C10 six-membered 1,3-dioxane
ring adopts an almost ideal OC3 (O4CC6) conformation slightly
shifted to the E5 direction. Similarly, for compound (II), the
ꢁ
˚
puckering parameters Q = 0.2810 (11) A and ’ = 110.4 (2) ,
and the relevant torsion angles (Table 3) are indicative of an
E3 (EO3) conformation for the O2/C2/C3/O3/C7 five-
membered 1,3-dioxolane ring. Analogously, considering the
values of the relevant torsion angles (Table 3) and the puck-
ꢁ
˚
ering parameters Q = 0.3958 (11) A and ’ = 123.07 (16) , the
five-membered O5/C2–C5 furanose ring adopts a T3 (C5TC4)
conformation.
4
Although the presence of a 1,3-dioxane ring fused to a
furanose ring at the 4,6-positions imposes some conforma-
tional rigidity on (I), its influence on the conformations of the
To date, only a few crystal structures of this general type
have been described. Among them, the most closely related
structure is 2,3:4,6-di-O-isopropylidene-ꢀ-l-xylo-hex-2-ulo-
sonic acid (2,3:4,6-di-O-isopropylidene-2-keto-l-gulonic acid)
[CSD (Allen, 2002) refcode DIPKGA; Takagi & Jeffrey, 1978].
4
furanose (in a significant shift of E3 ! T3) and 1,3-dioxolane
rings is, as seen from comparison with (II), negligible (see
Fig. 3). The most dramatic change in the conformation is
ꢂ
o152 Langer et al. C12H20O6 and C9H16O6
Acta Cryst. (2009). C65, o151–o154

organic compounds
Table 2
Hydrogen-bonding geometry for (II) (A, ).
apparent in the C2—C1—O1—H1 torsion angle, which has
values of 8 and 127ꢁ for (I) and (II), respectively.
ꢁ
˚
The hydrogen-bonding patterns are very different in the
two compounds. For (I), there is one strong intramolecular
O—Hꢀ ꢀ ꢀO hydrogen bond (Fig. 1) and some weak inter-
molecular C—Hꢀ ꢀ ꢀO hydrogen bonds (see Table 1 for details).
For (II), there are strong O—Hꢀ ꢀ ꢀO hydrogen bonds, one
intramolecular (denoted as a in Table 2) and two inter-
molecular (b and c), together with other weak intermolecular
C—Hꢀ ꢀ ꢀO hydrogen bonds (Table 2). On the first-level graph-
set, defined by Bernstein et al. (1995) and Grell et al. (1999),
string S(7) (bond a) and chains C(8) (b) and C(6) (c) were
identified. On the second-level graph-set, chains C22(9) and
C22(14) formed by hydrogen bonds b and c could be recog-
nized. On the third-level graph set, rings R55(21) can be found
(a, b and c; see Fig. 4 and Table 2).
Label
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
a
b
c
d
e
O4—H4ꢀ ꢀ ꢀO1
O1—H1ꢀ ꢀ ꢀO6i
O6—H6ꢀ ꢀ ꢀO4ii
C8—H8Aꢀ ꢀ ꢀO5iii
C9—H9Cꢀ ꢀ ꢀO3iv
0.84
0.84
0.84
0.98
0.98
1.95
1.94
1.95
2.45
2.55
2.7638 (13)
2.7708 (13)
2.7730 (12)
3.3682 (15)
3.4508 (16)
164
168
165
155
154
Symmetry codes: (i) x + 1, y, z; (ii) ꢃx + 1, y ꢃ , ꢃz + 12; (iii) x ꢃ , ꢃy + 21, ꢃz; (iv) x + 21,
1
2
1
2
ꢃy + 32, ꢃz.
Table 3
Selected torsion angles (ꢁ) for (I) and (II).
(I)
(II)
O2—C2—C3—O3
C7—O3—C3—C2
C3—O3—C7—O2
C2—O2—C7—O3
C7—O2—C2—C3
13.8 (2)
ꢃ25.6 (2)
27.7 (2)
ꢃ18.3 (2)
16.32 (11)
ꢃ29.03 (10)
30.81 (11)
ꢃ19.73 (12)
2.05 (12)
Experimental
2.7 (2)
Compound (I) was prepared according to a slight modification of the
procedure of Slobodin (1947) (fast neutralization under efficient
cooling using NaOH instead of KHCO3; four extractions with ethyl
acetate instead of 11 extractions with CHCl3 was deemed sufficient).
Compound (II) was obtained by heating (I) in 60% acetic acid at
348 K for 40 min, followed by evaporation of the solvent under
reduced pressure and crystallization of the product from a mixture of
ethyl acetate and hexane. The analytical data for (I) and (II) were in
accordance with those published previously (Szarek et al., 1997;
Beaupere et al., 1989). Colourless single crystals of a quality adequate
for diffraction analysis were obtained by slow crystallization of (I)
from a 2:1 (v/v) mixture of diethyl ether and n-hexane under
moderate cooling in a refrigerator. Analogous crystallization using a
mixture of ethyl acetate and n-hexane (2:1 v/v) afforded suitable
crystals of (II).
O5—C2—C3—C4
C2—C3—C4—C5
C3—C4—C5—O5
C2—O5—C5—C4
C5—O5—C2—C3
10.8 (2)
ꢃ29.7 (2)
38.5 (2)
13.88 (11)
ꢃ32.62 (10)
40.80 (10)
ꢃ33.6 (2)
ꢃ34.03 (10)
14.5 (2)
12.61 (11)
O4—C4—C5—C6
C4—C5—C6—O6
C10—O6—C6—C5
C6—O6—C10—O4
C4—O4—C10—O6
C10—O4—C4—C5
44.4 (3)
ꢃ45.0 (3)
53.1 (3)
ꢃ59.2 (3)
59.8 (3)
ꢃ52.7 (3)
Refinement
R[F2 > 2ꢄ(F2)] = 0.037
wR(F2) = 0.098
S = 1.00
168 parameters
H-atom parameteꢃrs3 constrained
Compound (I)
˚
Áꢅmax = 0.20 e A
ꢃ3
˚
1483 reflections
Áꢅmin = ꢃ0.24 e A
Crystal data
3
˚
C12H20O6
Mr = 260.28
Orthorhombic, P212121
V = 1371.1 (6) A
Z = 4
Compound (II)
Mo Kꢀ radiation
ꢃ = 0.10 mmꢃ1
T = 153 (2) K
0.78 ꢄ 0.48 ꢄ 0.32 mm
˚
a = 6.7203 (16) A
˚
b = 9.286 (2) A
˚
c = 21.972 (5) A
Crystal data
3
˚
V = 1056.34 (9) A
Z = 4
C9H16O6
Mr = 220.22
Data collection
Orthorhombic, P212121
˚
˚
b = 9.1945 (5) A
˚
c = 17.0658 (9) A
Mo Kꢀ radiation
ꢃ = 0.12 mmꢃ1
T = 153 (2) K
1.08 ꢄ 1.06 ꢄ 0.54 mm
a = 6.7321 (3) A
Bruker SMART CCD area-detector
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.440, Tmax = 0.969
15054 measured reflections
1483 independent reflections
1236 reflections with I > 2ꢄ(I)
Rint = 0.067
Data collection
Bruker SMART CCD area-detector
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.690, Tmax = 0.940
19061 measured reflections
2219 independent reflections
2019 reflections with I > 2ꢄ(I)
Rint = 0.037
Table 1
Hydrogen-bond geometry (A, ) for (I).
ꢁ
˚
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
O1—H1ꢀ ꢀ ꢀO4
C1—H1Aꢀ ꢀ ꢀO5i
C4—H4ꢀ ꢀ ꢀO1ii
C8—H8Aꢀ ꢀ ꢀO5iii
0.84
0.99
1.00
0.98
2.17
2.59
2.49
2.50
2.933 (3)
3.551 (3)
3.278 (3)
3.462 (3)
151
165
135
166
Refinement
R[F2 > 2ꢄ(F2)] = 0.031
wR(F2) = 0.082
S = 1.00
141 parameters
H-atom parameteꢃrs3 constrained
˚
Áꢅmax = 0.27 e A
ꢃ3
1
2
3
2
1
2
3
2
˚
Symmetry codes: (i) x þ ; ꢃy þ ; ꢃz; (ii) x ꢃ 1; y; z; (iii) x ꢃ ; ꢃy þ ; ꢃz.
2219 reflections
Áꢅmin = ꢃ0.23 e A
ꢂ
Acta Cryst. (2009). C65, o151–o154
Langer et al. C12H20O6 and C9H16O6 o153

organic compounds
In the absence of significant resonant scattering, the Friedel-
equivalent reflections were merged for compounds (I) and (II), and
therefore the absolute configuration of the molecules in (I) and (II)
were not determined by diffraction techniques. However, the abso-
lute configuration at chiral atoms C2, C3, C4 and C5 in (I) and (II)
was assigned on the basis of the known arrangement in
l-sorbofuranose derivatives, because isopropylidenation at O4 and
O6 does not affect the arrangements of atoms O3, O4 and O5 with
respect to the furanose ring in (I) and acetonation at O2 and O3
affords preferentially the cis-2,3-O-isopropylidenated product with
an ꢀ configuration at anomeric atom C2. For secondary H atoms, the
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GG3193). Services for accessing these data are
described at the back of the journal.
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˚
˚
C—H distance was fixed at 0.99 A and for tertiary at 1.00 A. For
˚
the methyl groups, the C—H distances (0.98 A) and C—C—H
ꢁ
˚
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and 1.5Ueq(O).
)
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The financial support of this work by the Scientific Grant
Agency (VEGA, Slovak Academy of Sciences, grant No.
2/0128/08) and by the Slovak Research and Development
Agency (APVV, Ministry of Education, grant No. APVV-
0366–07) is gratefully acknowledged.
ꢂ
o154 Langer et al. C12H20O6 and C9H16O6
Acta Cryst. (2009). C65, o151–o154