3-O-acetyl-4-deoxy-4-iodo-β-D-fructofuranosyl 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-D-glucopyranoside

Article abstract of DOI:10.1107/S0108270101009994

At 160 K, the glucopyranosyl ring of the title compound, C₂₀H₂₈ClIO₁₃, has a near-ideal ⁴C₁ conformation and the fructofuranosyl ring has a twist ⁴T₃ conformation. The two hydroxy groups are involved in intra- and intermolecular hydrogen bonds, with the latter interactions linking the molecules into infinite one-dimensional chains. The absolute configuration of the molecule has been determined.

Full text of DOI:10.1107/S0108270101009994

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
acetyl-1,4,6-trichloro-1,4,6-trideoxy-ꢁ-d-tagatofuranosyl 2,3,6-
tri-O-acetyl-4-chloro-4-deoxy-ꢂ-d-galactopyranoside (Lee et
al., 1999). The torsion angles (Table 1) about the anomeric O1
atom are also very similar to those in sucrose (Brown & Levy,
1973). The acetoxymethyl and hydroxymethyl groups of the
two sugar moieties all have the gauche±gauche conformation.
In sucrose, however, the hydroxymethyl substituents at C5 and
C50 (equivalent to C5 and C10 in Fig. 1) are gauche±gauche,
while that at C20 (equivalent to C7 in Fig. 1) is trans±gauche
(Brown & Levy, 1973). These gauche±gauche conformations in
compound (I) position the respective acetoxy and hydroxy
groups so as to avoid possible peri interactions, namely O6
with Cl4, O11 with I9, and O12 with both O8 and O10.
Interestingly, in 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-
ꢁ-d-tagatofuranosyl 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-ꢂ-d-
galactopyranoside (Lee et al., 1999), the C5-hydroxymethyl
substituent adopts a gauche±trans conformation. Since the
pyranosyl ring in this latter sugar is the galacto isomer, the
gauche±trans conformation positions the O atom bonded to
C6 anti to Cl4.
ISSN 0108-2701
3-O-Acetyl-4-deoxy-4-iodo-b-D-
fructofuranosyl 2,3,6-tri-O-acetyl-4-
chloro-4-deoxy-a-D-glucopyranoside
Anthony Linden,a* C. Kuan Leeb and A. S. Muhammad
Sofianb
aInstitute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190,
È
CH-8057 Zurich, Switzerland, and bDepartment of Chemistry, National University
È
of Singapore, Kent Ridge, Singapore 119260
Correspondence e-mail: alinden@oci.unizh.ch
Received 13 June 2001
Accepted 15 June 2001
4
The glucopyranosyl ring in compound (I) adopts the C1
chair conformation. The puckering parameters (Cremer &
At 160 K, the glucopyranosyl ring of the title compound,
C20H28ClIO13, has a near-ideal 4C1 conformation and the
4
fructofuranosyl ring has a twist T3 conformation. The two
Ê
Ê
Pople, 1975) are: Q = 0ꢁ.592 (3) A, q2 = 0.020 (2) A, q3 =
ꢁ
Ê
0.592 (3) A, '2 = 174 (8) and ꢃ = 1.7 (2) . The puckering
amplitudes (q3 >> q2) of the pyranose ring describe a very
slightly distorted chair. Indeed, the total puckering amplitude
(Q) is only slightly lower than that of the ideal cyclohexane
hydroxy groups are involved in intra- and intermolecular
hydrogen bonds, with the latter interactions linking the
molecules into in®nite one-dimensional chains. The absolute
con®guration of the molecule has been determined.
Ê
Ê
chair [0.63 A for d(CÐC) = 1.54 A]. The magnitude of the
distortion is signi®cantly smaller than in sucrose (ꢃ = 5.2ꢁ;
Cremer & Pople, 1975) and both peracylated 1,4,6-trichloro-
1,4,6-trideoxy-ꢁ-d-fructofuranosyl 4-chloro-4-deoxy-ꢂ-d-gal-
actopyranoside and 1,4,6-trichloro-1,4,6-trideoxy-ꢁ-d-tagato-
furanosyl 4-chloro-4-deoxy-ꢂ-d-galactopyranoside [ꢃ = 4.7 (5)
and 5.0 (3)ꢁ, respectively; Lee et al., 1999], but comparable
with that of sucralose (ꢃ = 1.9ꢁ; Kanters et al., 1988). With '2
being close to 180ꢁ, the distortion is towards the inverted boat
B3,0 conformation, which is very close to the conformational
distortion found in sucrose.
Comment
The Shallenberger and Acree±Kier AH,B,ꢀ tripartite
hypothesis (Shallenberger & Acree, 1967; Kier, 1972) is
currently the most widely accepted explanation for sweetness.
However, the location of the AH,B,ꢀ glucophore in many
classes of high intensity sweeteners is still far from de®ned
(Mathlouthi et al., 1993; Suami et al., 1994). Our studies are
aimed at trying to locate this tripartite glucophore and the
determination of the sweet conformation of the intensely
sweet halodeoxy sucrose sweeteners. As part of this
programme, the low-temperature crystal structure of the title
compound, (I), has been determined.
4
The furanoid ring in compound (I) has a T3 twist confor-
mation [ꢃ = 277.1 (3)ꢁ], which is the same as in sucrose
(Rohrer, 1972) and 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-
ꢁ-d-fructofuranosyl 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-ꢂ-d-
galactopyranoside (Lee et al., 1999). The twist is on C8 and C9,
Ê
with these atoms being 0.205 (6) and 0.479 (6) A, respec-
tively, from the plane de®ned by C7, C10 and O10.
It is now generally believed that the AH,B unit of the
Shallenberger and Acree±Kier AH,B,ꢀ glucophore (Shallen-
berger & Acree, 1967; Kier, 1972) spans the two sugar rings of
sucrose (Mathlouthi et al., 1993). From molecular mechanics
and dynamics studies, Hooft et al. (1993) suggested that the
sweet conformation of the sweet chlorinated sucroses should
have values for the torsion angles de®ned by È(C1ÐO1Ð
C7ÐO10) and É(C7ÐO1ÐC1ÐO5) of 75 and 95ꢁ, respec-
tively. In (I), these torsion angles are 42.5 (3) and 104.7 (2)ꢁ,
respectively, which are very similar to those of sucrose
[ 44.75 (11) and 107.82 (10)ꢁ, respectively; Brown & Levy,
1973] and two reported chlorinated sucrose analogues, namely
The absolute con®guration of (I) has been con®dently
determined by re®nement of the absolute structure parameter
and is shown in Fig. 1. The bond lengths and angles exhibit
normal values and generally agree with those of sucrose
(Brown & Levy, 1963, 1973; Hanson et al., 1973) and 3-O-
ꢀ
1098 # 2001 International Union of Crystallography
Printed in Great Britain ± all rights reserved
Acta Cryst. (2001). C57, 1098±1100

organic compounds
for 15 min and then at 273 K for 2 h. The reaction mixture was
worked up in the usual way and treated with LiCl (0.15 g) in acetone
to give, after ¯ash chromatography (ether/hexane, 1:1), 3-O-acetyl-4-
deoxy-4-iodo-1,6-di-O-trityl-ꢁ-d-fructofuranosyl 2,3,6-tri-O-acetyl-4-
chloro-4-deoxy-ꢂ-d-glucopyranoside (0.5 g, 70%), m.p. 366±368 K;
3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-ꢁ-d-fructofuranosyl
2,3,6-tri-O-acetyl-4-chloro-4-deoxy-ꢂ-d-galactopyranoside
[È = 25.1 (5)ꢁ and É = 99.5 (4)ꢁ] and 3-O-acetyl-1,4,6-tri-
chloro-1,4,6-trideoxy-ꢁ-d-tagatofuranosyl 2,3,6-tri-O-acetyl-4-
chloro-4-deoxy-ꢂ-d-galactopyranoside [È = 48.0 (3)ꢁ and
É = 113.1 (2)ꢁ] (Lee et al., 1999), but are very different from
those of another chlorinated sucrose analogue, viz. sucralose
[È = 162.2 (2)ꢁ and É = 91.4 (2)ꢁ; Kanters et al., 1988].
The hydroxy group at O12, which is part of the hydroxy-
methyl group adjacent to the bridging O atom, is involved in
bifurcated hydrogen bonds. One is a weak intramolecular
interaction with the ring O atom of the furanoid ring, forming
1
[ꢂ]D +34.9ꢁ (c 0.57, CHCl3); H NMR (CDCl3, ꢄ, p.p.m.): 1.62, 1.94,
0
0
1.96, 2.07 (4 Â s, 12H, 4 Â CH3), 3.06±3.19 (2 Â d, 2H, J1 a,1 b = 9.7 Hz,
H10a,b), 3.3±3.4 (m, 2H, H60a,b), 3.69 (t, 1H, J3,4 = J4,5 = 10.1 Hz, H4),
4.1±4.3 (m, 5H, H40, 5, 50, 6a,b), 4.54 (dd, 1H, J1,2 = 3.8, J2,3 = 10.1 Hz,
H2), 5.27 (t, 1H, J2,3 = J3,4 = 10.1 Hz, H3), 5.60 (d, 1H, J1,2 = 3.8 Hz,
H1), 5.92 (d, 1H, J3 ,4 = 9.7 Hz, H30) and 7.1±7.4 (m, 30H, Ar-H); 13C
NMR: ꢄ 170.3, 169.5, 169.4, 169.1 (COCH3), 143.6, 143.5 (CPh3),
128.8, 128.7, 127.8, 127.1 (Ar-C), 103.9 (C20), 88.6 (C1), 83.8 (C50),
80.1 (C30), 71.3, 70.4, 70.3 (C2, C3, C5), 65.0, 63.2, 62.2 (C10, C6, C60),
55.4 (C4), 21.0, 20.6, 20.5, 20.3 (COCH3) and 18.4 (C40); HRMS±ESI
(positive mode), calculated for [M + Na]+: 1145.2352:1147.2322;
found: 1145.2370:1147.2375 (3:1). The above 4-chloro-40-iodo deri-
vative (0.42 g, 0.37 mmol) was dissolved in ice-cold CH2Cl2/AcOH
(1:1, 10 ml) and treated with concentrated HCl (0.080 ml) at room
temperature for 30 min to give, after ¯ash chromatography (ethyl
acetate/hexane, 1:1), the title compound, (I) (0.18 g, 75%), m.p. 386±
0
0
1
387 K; [ꢂ]D +5.92ꢁ (c 0.76, CHCl3); H NMR (CDCl3, ꢄ, p.p.m., the
assignments employ the crystallographic atom numbering used in
Fig. 1): 1.99, 2.03, 2.06, 2.20 (4 Â s, 12H, 4 Â CH3), 3.45±3.90 (m, 5H,
H4, 12a,b, 11a,b), 4.17±4.44 (m, 5H, H9, 5, 10, 6a,b), 4.75 (dd, 1H, J1,2
=
3.5, J2,3 = 10.2 Hz, H2), 5.40 (d, 1H, J8,9 = 10.4 Hz, H8), 5.41 (t, 1H,
J2,3 = J3,4 = 10.2 Hz, H3) and 5.58 (d, 1H, J1,2 = 3.5 Hz, H1); 13C NMR:
ꢄ 170.7, 170.4, 170.1, 169.5 (COCH3), 104.3 (C7), 89.5 (C1), 85.4
(C10), 80.5 (C8), 71.1, 70.8, 70.5 (C2, 3, 5), 64.3, 62.2, 58.7 (C12, 6, 11),
54.9 (C4), 20.7, 20.6, 20.5, 20.4 (COCH3) and 16.2 (C9); HRMS±ESI
(positive mode), calculated for [M + Na]+: 661.0161:663.0131; found:
661.0164:663.0105 (3:1). Suitable crystals were obtained by very slow
evaporation of a solution of compound (I) in chloroform.
Crystal data
C20H28ClIO13
Mr = 638.77
Orthorhombic, P212121
Mo Kꢂ radiation
Cell parameters from 39 653
re¯ections
Figure 1
ꢃ = 2.0±30.0ꢁ
Ê
a = 8.8407 (1) A
b = 10.5562 (1) A
View of the molecule of (I) showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 50% probability level. H atoms
are represented by circles of arbitrary size.
1
Ê
Ê
ꢅ = 1.38 mm
T = 160 (1) K
c = 28.2974 (4) A
Ê
V = 2640.83 (5) A
3
Prism, colourless
0.35 Â 0.22 Â 0.20 mm
Z = 4
Dx = 1.607 Mg m
3
a ®ve-membered loop with a graph-set motif of S(5) (Bern-
stein et al., 1995), while the other interaction is a stronger
intermolecular hydrogen bond with the carbonyl O atom of
the acetoxymethyl substituent at C5 of the glucopyranosyl ring
of a neighbouring molecule (Table 2). These interactions link
the molecules into in®nite one-dimensional chains which run
parallel to the [100] direction and have a graph-set motif of
C(10). The hydroxy group at O11 participates in an intramo-
lecular hydrogen bond with the ring O atom of the gluco-
pyranosyl ring. This results in the formation of a nine-
membered loop with a graph-set motif of S(9).
Data collection
Nonius KappaCCD diffractometer
' and ! scans with ꢆ offsets
Absorption correction: multi-scan
(Blessing, 1995)
Tmin = 0.679, Tmax = 0.786
27 635 measured re¯ections
7621 independent re¯ections
6659 re¯ections with I > 2ꢇ(I)
Rint = 0.044
ꢃmax = 30.0ꢁ
h = 12 ! 12
k = 14 ! 14
l = 38 ! 39
Re®nement
Re®nement on F2
R[F2 > 2ꢇ(F2)] = 0.035
wR(F2) = 0.076
(Á/ꢇ)max = 0.001
3
Ê
Áꢈmax = 1.99 e A
3
Ê
1.23 e A
Áꢈmin
=
S = 1.03
7621 re¯ections
323 parameters
H-atom parameters constrained
w = 1/[ꢇ2(Fo2) + (0.0193P)2
+ 2.6788P]
Extinction correction: SHELXL97
Extinction coef®cient: 0.0015 (4)
Absolute structure: Flack (1983),
3319 Friedel pairs
Experimental
A solution of 3-O-acetyl-4-deoxy-4-iodo-1,6-di-O-trityl-ꢁ-d-fructo-
furanosyl 2,3,6-tri-O-acetyl-ꢂ-d-galactopyranoside (0.7 g) (Muham-
mad So®an & Lee, 2001) in dry CH2Cl2/pyridine (15:1, 32 ml) was
treated with tri¯uoromethane sulfonic anhydride (0.2 ml) at 195 K
Flack parameter = 0.021 (14)
2
2
where P = (Fo + 2Fc )/3
ꢀ
Acta Cryst. (2001). C57, 1098±1100
Linden et al. C20H28ClIO13 1099

organic compounds
Table 1
Selected geometric parameters (A, ).
Data collection: COLLECT (Nonius, 2000); cell re®nement:
DENZO-SMN (Otwinowski Minor, 1997); data reduction:
ꢁ
Ê
&
DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997);
program(s) used to solve structure: SIR92 (Altomare et al., 1994);
program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997);
molecular graphics: ORTEPII (Johnson, 1976); software used to
prepare material for publication: SHELXL97.
O1ÐC1
O1ÐC7
O5ÐC1
1.413 (3)
1.426 (3)
1.420 (3)
O5ÐC5
O10ÐC7
O10ÐC10
1.442 (3)
1.416 (3)
1.453 (3)
C1ÐO1ÐC7
117.35 (18)
C7ÐO1ÐC1ÐO5
C7ÐO1ÐC1ÐC2
C17ÐO6ÐC6ÐC5
O5ÐC5ÐC6ÐO6
C4ÐC5ÐC6ÐO6
C1ÐO1ÐC7ÐO10
C1ÐO1ÐC7ÐC12
104.7 (2)
135.5 (2)
179.2 (2)
71.8 (3)
48.5 (3)
42.5 (3)
76.3 (3)
C1ÐO1ÐC7ÐC8
156.28 (19)
64.4 (3)
50.9 (4)
58.3 (3)
179.6 (2)
59.4 (3)
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK1489). Services for accessing these data are
described at the back of the journal.
O10ÐC10ÐC11ÐO11
C9ÐC10ÐC11ÐO11
O10ÐC7ÐC12ÐO12
O1ÐC7ÐC12ÐO12
C8ÐC7ÐC12ÐO12
References
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Table 2
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ꢁ
Ê
Brown, G. M. & Levy, H. A. (1963). Science, 141, 921±923.
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DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
O11ÐH11Á Á ÁO5
O12ÐH12Á Á ÁO10
O12ÐH12Á Á ÁO17i
0.84
0.84
0.84
2.25
2.38
2.16
2.964 (3)
2.773 (2)
2.952 (3)
143
109
158
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1
2
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(1988). Carbohydr. Res. 180, 175±182.
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The methyl and hydroxy H atoms were constrained to an ideal
Ê
geometry (0.98 and 0.84 A, respectively), with Uiso(H)
=
1.5Ueq(parent atom), but were allowed to rotate freely about the CÐ
C and CÐO bonds. All other H atoms were placed in geometrically
Ê
idealized positions (CÐH = 0.99±1.00 A) and constrained to ride on
their parent atoms, with Uiso(H) = 1.2Ueq(C). The determined abso-
lute structure agreed with that expected for a natural sucrose deri-
vative. The largest and the most negative peaks of residual electron
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È
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Ê
density were within 0.9 A of the I atom.
ꢀ
1100 Linden et al. C20H28ClIO13
Acta Cryst. (2001). C57, 1098±1100