Macrocyclic receptors containing sucrose skeleton

Article abstract of DOI:10.1016/j.tet.2005.06.046

Crown ether analogues with incorporated sucrose unit were prepared by reaction of 1′,2,3,3′,4,4′-hexa-O-benzylsucrose with polyethylene ditosylates in up to 52% yield. Stability constants of their complexes with Li⁺, Na⁺, K⁺, NH ₄⁺ were determined by the NMR titration method. The macrocycles were also tested as catalysts in the enantioselective Michael reaction, but with little success (ee up to only 22%). The macrocycle containing nitrogen in the ring was also prepared in good yield. All prepared macrocycles were easily converted into the free sucrose crowns (H₂/Pd/C) without destroying the (very labile) glycosidic bond. The crystal structure of the selected receptor was determined.

Full text of DOI:10.1016/j.tet.2005.06.046

Tetrahedron 61 (2005) 8485–8492
Macrocyclic receptors containing sucrose skeleton
a
a
b
Sławomir Jarosz,a, Arkadiusz Listkowski, Bartosz Lewandowski, Zbigniew Ciunik
*
and Anna Brzuszkiewiczb
aInstitute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
bFaculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland
Received 20 April 2005; revised 24 May 2005; accepted 16 June 2005
Available online 20 July 2005
Abstract—Crown ether analogues with incorporated sucrose unit were prepared by reaction of 10,2,3,30,4,40-hexa-O-benzylsucrose with
polyethylene ditosylates in up to 52% yield. Stability constants of their complexes with LiC, NaC, KC, NH4C were determined by the NMR
titration method. The macrocycles were also tested as catalysts in the enantioselective Michael reaction, but with little success (ee up to only
22%). The macrocycle containing nitrogen in the ring was also prepared in good yield. All prepared macrocycles were easily converted into
the free sucrose crowns (H2/Pd/C) without destroying the (very labile) glycosidic bond. The crystal structure of the selected receptor was
determined.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
analogues modified at the terminal positions. The primary
hydroxyl group in 2 can be differentiated, allowing the
preparation of a number of sucrose derivatives, which—
after removing the benzyl protecting groups—can be
obtained in a free form.3 Also, the diol 3 was prepared
readily from 2.5 Recently, we prepared in high overall yield
(48%) even more convenient dihydroxylated sucrose
derivative: the hexa-O-benzylated diol 4.6
Sucrose (1) represents of a cheap raw material and is
available in more than 100 million tons per year; most of it
being consumed on the food market. This disaccharide is
also a subject of interest for many laboratories, which apply
it in chemical synthesis. For example, it maybe used for the
preparation of bio-degradable polymers and surfactants,1 or
applied as a chiral matrix for the synthesis of complex
natural products.2,3 The very high purity of commercially
available sucrose allows the use of this compound as a
source of chirality for chemical synthesis without any
additional purification.
2. Results and discussion
Easy access to the diol 4 opened the possibility for the
preparation of the crown ether analogues with incorporated
sucrose unit, in which the C-6 and C-60 positions are
connected via a heteroatomic bridge (Fig. 1).
Recently we synthesized several such derivatives (5a–9a)6,7
albeit in moderate yields (ca. 12% for 5a up to 31% for 9a)
by reaction of the diol 4 with the corresponding
polyethylene ditosylates. By the improved procedure
reported here, these yields are now improved up to 52%.
The important feature of this methodology lies in the easy
deprotection of the macrocycles without destroying the very
labile glycosidic bond. Simple hydrogenolysis removes the
benzyl protecting groups and allows to obtain the free
compounds, further isolated as peracetates 5b–11b.
As a part of an on-going program, we elaborated a
convenient route to 2,3,30,4,40-penta-O-benzyl-sucrose4
(2), a convenient starting material for the preparation of
The structure of one of these derivatives—7b—was
assigned by X-ray analysis. The numbering scheme and
overall conformation of 7b is shown in Figure 2. The
Keywords: Sucrose; Chiral receptors; Crown ether analogues.
*
Corresponding author. Tel.: C48 22 3432322; fax: C48 22 6326681;
e-mail: sljar@icho.edu.pl
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.046

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S. Jarosz et al. / Tetrahedron 61 (2005) 8485–8492
Figure 1. Preparation of sucrose-based crown ether analogues.
asymmetric part of the crystal consists of two symmetry
independent molecules A and B. The sucrose units of both
molecules are very similar. The Cremer and Pople ring-
puckering parameters8,9 Q, q and f (calculated using
program PUCK210) for glucopyranoid rings of molecules
˚
A and B [0.581(7) A, 6.6(7)8, 309(6)8 and 0.583(7) A,
˚
4
5.8(6)8, 312(6)8] indicate the typical C1(D)-chair confor-
mation and for the furanoid rings the q2 and f2 parameters
Figure 2. X-ray structure of compound 7b.

S. Jarosz et al. / Tetrahedron 61 (2005) 8485–8492
8487
Table 1. Selected torsion angles (8)
Molecule A (iZ0)
Molecule B (iZ50)
C(5Ci)–O(1Ci)–C(1Ci)–O(7Ci)
C(1Ci)–O(1Ci)–C(5Ci)–C(6Ci)
O(1Ci)–C(5Ci)–C(6Ci)–O(2Ci)
C(7Ci)–O(2Ci)–C(6Ci)–C(5Ci)
C(6Ci)–O(2Ci)–C(7Ci)–C(8Ci)
O(2Ci)–C(7Ci)–C(8Ci)–O(3Ci)
C(9Ci)–O(3Ci)–C(8Ci)–C(7Ci)
C(8Ci)–O(3Ci)–C(9Ci)–C(14Ci)
O(3Ci)–C(9Ci)–C(14Ci)–O(4Ci)
C(15Ci)–O(4Ci)–C(14Ci)–C(9Ci)
C(14Ci)–O(4Ci)–C(15Ci)–C(16Ci)
O(4Ci)–C(15Ci)–C(16Ci)–O(5Ci)
C(17Ci)–O(5Ci)–C(16Ci)–C(15Ci)
C(16Ci)–O(5Ci)–C(17Ci)–C(18Ci)
O(5Ci)–C(17Ci)–C(18Ci)–O(6Ci)
C(21Ci)–O(6Ci)–C(18Ci)–C(17Ci)
C(18Ci)–O(6Ci)–C(21Ci)–O(7Ci)
C(1Ci)–O(7Ci)–C(21Ci)–O(6Ci)
C(21Ci)–O(7Ci)–C(1Ci)–O(1Ci)
56.4(7)
K171.3(5)
K68.7(6)
K163.6(5)
93.9(7)
K66.7(8)
K89.6(8)
151.1(6)
K7.2(9)
178.5(6)
170.2(6)
K76.7(7)
K163.1(5)
179.7(5)
67.3(7)
58.6(7)
K169.3(5)
K75.0(6)
169.1(6)
77.4(8)
K67.0(9)
175.1(6)
K146.1(7)
8.9(9)
K175.5(6)
K174.5(6)
K67.0(7)
K160.8(5)
179.9(5)
68.9(7)
93.6(6)
95.9(6)
K99.6(6)
K86.5(6)
63.2(7)
K94.7(6)
K88.7(6)
65.2(7)
[0.259(7), 142(2) and 0.218(6), 14(2)] indicate the
18E-envelope [with the C(18) atom in the apex] and the
did not afford any diester. Compound 14a was easily
converted into the peracetylated analogue 14b by simple
hydrogenolysis followed by acetylation.
71
T
twist conformations, respectively.
70
This difference has rather a minor influence on the crown
ring conformation. The respective torsion angles listed in
Table 1, which characterize this part of molecules have very
similar values. On the other hand, the molecules A and B
have different conformations near the aromatic ring. The
C(9)–O(3)–C(8)–C(7) and C(59)–O(53)–C(58)–C(57)
torsion angles are equal K89.6(8) and 175.1(6)8, and the
C(8)–O(3)–C(9)–C(14) and C(58)–O(53)–C(59)–C(64) are
equal 151.1(6) and K146.1(7)8, respectively.
Reaction of 15 with benzylamine, which would provide the
direct precursor of 14-imide 16—was unsuccessful. Also
trans-esterification of 15 into dimethyl ester (which should
react with benzylamine more readily than 15) under various
conditions failed.
The 1,4-addition of nucleophiles to a,b-unsaturated ketones
catalyzed by chiral crown ethers may provide the
corresponding adducts in high optical purity. One such
reaction is the addition of 2-nitropropane to chalcone
leading to 1,4-adducts 17. When such catalysts based on
simple sugar were used, the optical purity of 17 amounted to
95%.11 We tested our analogues in such a process, however,
with no success. Optical purities of product 17 in the
reaction catalyzed by sucrose crowns were very low and did
not exceed 22% (see Table 2).
The starting material for the preparation of the aza-analogue
14a—the diol 12—was synthesized by two different routes
from 4 (Scheme 1). The first involved double allylation
followed by cleavage of the double bonds with OsO4/NaIO4
and subsequent reduction. The second was based on the
reaction of the diol 4 with t-butyl bromoacetate and
reduction of the resulting diester 15 with LiAlH4. The
second method afforded diol 12 in higher yield (66 vs 49%).
Surprisingly, reaction of diol 4 with methyl bromoacetate
The stability constants of complexes formed can be easily
determined by NMR titration;12 the results obtained for
Scheme 1. (i) a. AllBr, NaH, DMF, 3 h, rt, 95%; b. OsO4, NaIO4, THF/H2O (1:1) then NaBH4 , 52%; (ii) a. MsCl, Et3N, DMAP, CH2Cl2, b. NaI, acetone,
reflux, 6 h, 69%; (iii) BnNH2, NaCO3, CH3CN, 50 h, reflux, 73%; (iv) BrCH2COt2Bu, 50% NaOH, toluene, Bu4NBr, 69%; (v) LiAlH4, THF, 95%.

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S. Jarosz et al. / Tetrahedron 61 (2005) 8485–8492
Table 2. Base-catalyzed 1,4-addition of 2-nitropropene to chalcone
catalyzed by sucrose crowns
Catalyst
Chemical yield %
17% ee
5a
6a
7a
8a
9a
10a
14a
88
88
77
56
85
9
15 (S)
22 (S)
13 (S)
9 (R)
17 (S)
16 (S)
17 (S)
Figure 3. Complexes of sugar derived macrocycles with t-bytulammonium
thiocyanate.
catalysts in enantioselective Michael reaction was not
successful.
66
sucrose receptors are shown in Table 3. The stability
constants are rather moderate; they depend on the cavity of
the macrocycle, but do not depend on the counter ion as can
be noticed for compound 7a (entry 2; Table 3). The highest
values were noted for complexes of 5a with sodium and
potassium and the aza-analogue 14a for potassium cation.
4. Experimental
4.1. General
1H NMR spectra were recorded with a Varian Mercury 400
BB (for 10b), or a Bruker DRX 500 spectrometers for
solutions in CDCl3 (internal Me4Si). NMR titration of
macrocycles with thiocyanates (and KPF6) was performed
with a Varian Gemini 2000 BB spectrometer in acetone-d6
according to a standard methodology.12,14 Most of the
The stability constants of complexes of sucrose receptors
were low. First (most likely) reason results from a distorted
crown structure of sucrose macrocycles described here.
Second one is a consequence of a sugar unit being part of a
macrocycle. It is reported, that the complexing abilities of
monosaccharide based crown ethers strongly depend on the
configuration of a sugar. For example, mannose derived
proton resonances were assigned by the H–1H- and the
1
carbon resonances in 5b by the 1H–13C- correlations. Mass
spectra (ESI) were recorded with PE SCIEX API 365, or
Mariner PerSeptive Biosystems apparatus. Optical rotations
were measured with a Digital Jasco polarimeter DIP-360
for solutions in chloroform (cZ1) at room temperature.
Column chromatography was performed on silica gel
(Merck, 70–230 or 230–400 mesh). THF was distilled
from potassium prior to use. For chromatography purposes
a fraction of mineral oil with a boiling point in range
70–90 8C was used as mixture of hexanes. All solutions
were dried over anhydrous sodium sulfate.
t
receptor 18 forms strong complex with butylammonium
thiocyanate (KaZ39,000 MK1), while analogous complex
of macrocycle 19—differing only in configuration at the
C-3 atom of the sugar skeleton—is very weak (Ka!50 MK1
see Fig. 3).13
3. Conclusion
X-ray data of 7b were collected at low temperature using an
Oxford Cryosystem device on a Kuma KM4CCD k-axis
diffractometer with graphite-monochromated Mo Ka radia-
The sucrose macrocycles—analogues of the crown ethers—
are easily prepared from ‘sucrose diol’, which has the C6
and C60 positions free and the other hydroxyl groups
protected as benzyl ethers. These macrocyclic derivatives
are easily converted into the free analogues by simple
hydrogenation. The complexing properties of the ‘crowns’
studied are rather moderate. The highest stability constant
with potassium ion was measured for compound 5a and 14a
having a 16-membered ring.
˚
tion (lZ0.71073 A). The crystal was positioned at 65 mm
from the CCD camera. 612 frames were measured at 0.758
intervals with a counting time of 20 s. Accurate cell
parameters were determined and refined by least-squares
fit of 3900 the strongest reflections. The data were corrected
for Lorentz and polarization effects. No absorption
correction was applied. Data reduction and analysis were
carried out with the Oxford Diffraction (Poland) Sp. z o.o.
programs. The structure was solved by direct methods
Application of such sucrose-derived macrocycles as
Table 3. Stability constants of 1:1 complexes (calculated from the shift of the H-1 signal) of ‘crown sucroses’ with cations (compound 6a formed complexes of
different stoichiometry); measured in acetone-d6
Compound
LiSCN
NaSCN
KSCN
NH4SCN
1.
2.
3.
4.
5.
6.
7.
5a
7a
7b
8a
9a
10a
14a
!5
250
31
9
19
60
14
258
57a
12
18
66
17
9
!5
7
25
!5
234
50
125
aKZ63 MK1 with KPF6.

S. Jarosz et al. / Tetrahedron 61 (2005) 8485–8492
8489
Table 4. Crystal data and structure refinement
sodium hydride (50% suspension in mineral oil, 110 mg ca.
2.25 mmol) and a catalytic amount of imidazole (30 mg)
were added under an argon atmosphere and the mixture
was stirred for 20 min at room temperature. The correspond-
ing ditosylate (0.98 mmol) in DMF (15 mL) was then
added dropwise over 30 min, and stirring was continued
for 12 h. The excess of hydride was then carefully
decomposed with water and the products were extracted
with ethyl acetate. The organic phase was washed with
water, dried, concentrated and the products 5a–11a were
isolated by column chromatography (eluent: hexane–ethyl
acetate).
Empirical formula
Formula weight
T/K
l/A
Crystal system
C34H44O19
756.69
100(2)
0.71073
Monoclinic
P21
17.645(19)
8.957(10)
22.74(3)
˚
Space group
˚
a/A
˚
b/A
˚
c/A
b/8
V/A
92.370(10)
3591(7)
3
˚
Z
4
1.400
0.115
1600
Dc/mg mK3
m/mmK1
F(000)
This preparation essentially followed the procedure applied
recently by us, except the solvent. When the reaction was
performed in THF the yields of macrocycles were low.6
However, changing the solvent to dry DMF increased the
yields significantly.
Crystal size/mm
q range for data collection/8
Ranges of h,k,l
Reflections collected
Independent reflections (Rint
Data/parameters
GOF(F2)
0.25!0.17!0.10
3.34–28.54
K23/22,K8/11,K30/29
25,113
11,423 (0.0816)
11,423/968
1.097
)
† Compound 6a, 35% (after column chromatography with
hexane/ethyl acetate, 2:1 to 1:1). Previously reported
yield: 12%.
Final R1/wR2 indices (IO2sI)
Extinction coefficient
˚
Largest diff. peak/hole (e A
0.0837/0.2093
0.0123(15)
0.330/K0.331
K3
)
† Compound 7a, 48% (after column chromatography with
hexane/ethyl acetate, 2:1, then HPLC with hexane/ethyl
acetate, 5:2). Previously reported yield: 15%.
† Compound 9a, 52% (after column chromatography with
hexane/ethyl acetate, 3:2). Previously reported yield:
31%.
(program SHELXS9715) and refined by the full-matrix
least-squares method on all F2 data using the SHELXL9716
program. Non-hydrogen atoms were refined with aniso-
tropic displacement parameters; hydrogen atoms were
included from geometry of molecules and Dr maps. During
the refinement their parameters were fixed. Crystal data are
given in Table 4, together with refinement details.
4.3.1. 10,2,3,30,4,40-Hexa-O-benzyl-6,60-O-(5,5-dimethyl-
3,7-dioxanonan-1,9-di-yl)-sucrose (10a). (Eluent: hexane/
ethyl acetate, 4:1, then HPLC). Colorless oil, [a]D C37.4.
Crystallographic data for the structures reported in this
paper (excluding structure factors) have been deposited with
the Cambridge Crystallographic Data Centre, CCDC No.
272641. Copies of this information may be obtained free of
charge from the Director, CCDC, 12 UNION Road,
Cambridge 1EZ, UK (fax: C44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
IR (film) n 3031, 2868, 1454, 1092, 1028, 736, 698 cmK1
;
1H NMR d: 5.66 (d, J1,2Z3.5 Hz, 1H, H-1), 0.86, 0.83 (2!
s, 2!3H, 2!CH3). 13C NMR d: 138.9, 138.72, 138.67,
138.47, 138.40, 138.3 (6!Cq benzyl), 104.1 (C-20), 89.4
(C-1), 83.4, 82.02, 81.99, 79.9, 79.7, 77.8 and 70.82
(C-2,3,30,4,40,5,50), 76.6, 76.4, 75.4, 74.7, 73.3, 72.65,
72.57, 72.55, 71.7 (double intensity), 71.0, 70.78, 70.75,
70.73, 69.6 (C-10,6,60, 6!OCH2Ph and 6!–OCH2–
from the macrocyclic ring) 36.1 (CMe2), 22.3, 22.1 (2!
CH3). m/z: 1061 [M(C63H74O13)CNaC]. Anal. Calcd
for C63H74O13: C, 72.81; H, 7.18. Found: C, 72.8; H,
7.2%.
4.2. Synthesis of the diol 4
This compound was prepared from 10,2,3,30,4,40-hexa-O-
benzyl-6,60-dichloro-6,60-dideoxysucrose according to Ref.
6 by substitution of both 6,60chlorine atoms with acetates
using 5 equiv of Bu4NOAc (75% yield) followed by
hydrolysis of acetates under Zemplen conditions.
4.3.2. 10,2,3,30,4,40-Hexa-O-benzyl-6,60-O-(1,2-diphen-
oxy-3-oxapentylidene)-sucrose (11a). (Eluent: hexane/
ethyl acetate, 1:1, then HPLC. Colorless oil, [a]D C40.2.
IR (film) n 2918, 2869, 1498, 1454, 1257, 1127, 1091, 1028,
738, 698 cmK1; 1H NMR d: 5.65 (d, J1,2Z3.6 Hz, 1H, H-1).
13C NMR d: 149.18, 149.13 (2!C from –C6H4–), 139.0,
138.7, 138.4, 138.34, 138.26, 138.0 (6!Cq benzyl), 121.6
(double intensity), 115.0, 114.7 (4!C from –C6H4–), 104.2
(C-20), 89.4 (C-1), 83.4, 81.9, 81.8, 79.9, 79.5, 77.9 and
71.08 (C-2,3,30,4,40,5,50), 75.4, 74.7, 73.3, 72.59, 72.58,
72.49, 71.8, 71.7, 71.1, 70.95, 70.92, 70.5, 69.84, 69.80,
69.7, 69.5, 69.4 (C-10,6,60, 6!OCH2Ph and 8!–OCH2–
from macrocyclic ring). m/z: 1155 [M(C68H76O15)CNaC].
Anal. Calcd for C68H76O15: C, 72.07; H, 6.76. Found: C,
72.3; H, 6.6%.
We have found that Bu4NOAc can be replaced with sodium
acetate without significant decrease of the yield of 6,60-
diacetate, although the time of this substitution is much
longer. Thus, to a0solution of 10,2,3,30,4,40-hexa-O-benzyl-
6,60-dichloro-6,6 -dideoxysucrose (400 mg) in DMF
(100 mL) anhydrous sodium acetate (2 g) was added and
the mixture was stirred at 100–110 8C for 20 days. After
cooling it was poured into the water (150 mL) and the
product was extracted with ether (3!100 mL) to afford
diacetate 4-Ac in (290 mg, 69%).
4.3. General procedure for the preparation of macro-
cycles 5a–11a
To a solution of 4 (0.66 g, 0.75 mmol) in dry DMF (25 mL),

8490
S. Jarosz et al. / Tetrahedron 61 (2005) 8485–8492
4.4. General procedure for deprotection of macrocycles;
synthesis of pearacetetas 5b–11b and 14b
(double intensity), 69.81, 69.3, 69.2, 63.1 (C-10,6,60 and 8!
–OCH2– from macrocyclic ring), 20.72, 20.67, 20.63
(double intensity), 20.57, 20.54 (6!COCH3). HRMS:
867.2926 [C38H52O21Na (MCNa)C requires: 867.2893].
Anal. Calcd for C38H52O21: C, 50.02; H, 6.20. Found: C,
49.8; H, 6.2%.
To a solution of the appropriate perbenzylated derivative (0.
4 mmol) in ethanol (7 mL), ethyl acetate (7 mL), and water
(0.1 mL), 10% Pd/C (20 mg) was added, and the mixture
was hydrogenolyzed for 24 h under standard conditions.
Solvents were removed in vacuum, the residue was
suspended in pyridine (5 mL), to which acetic anhydride
(2 mL) and DMAP (ca. 30 mg) were added and the mixture
was stirred at room temperature for 2 h. Products were
isolated by column chromatography.
4.4.4. 10,2,3,30,4,40-Hexa-O-acetyl-6,60-(3-azabenzyl-
penta-1,5-di-yl)-sucrose (14b). (Eluent: hexane/ethyl acet-
ate, 2:3–1:2). Yellowish oil, [a]D C28.1. IR (film) n 2929,
1
1748, 1643, 1370, 1224, 1046 cmK1; H NMR [Signals
from two conformers in ratio 1.72 (a-major) to 1 (b-minor)]
d: 5.64 (d, J1,2Z3.6 Hz, 1H, H-1, b), 5.57 (d, J1,2Z3.5 Hz,
1H, H-1, a), 2.22 (a), 2.20 (b), 2.12 (a), 2.112 (b), 2.107 (a),
2.104 (aCb), 2.90 (a), 2.072 (b), 2.067 (a), 2.063 (b), 2.01
(b), 2.00 (a), 1.96 (b) (7!s, 6!3H, 6!COCH3 from a and
7!s, 6!3H, 6!COCH3 from b). 13C NMR d: 170.9 (a),
170.7 (b), 170.07 (b), 170.06 (a), 170.00 (b), 169.98 (a),
169.93 (a), 169.90 (double intensity, 2!a), 169.88 (double
intensity, 2!b), 169.81 (b), 169.77 (b), 169.67 (a) (7!CO
from a and 7!CO from b), 103.7 (C-2, a), 103.4 (C-2, b),
90.0 (C-10, a), 89.6 (C-1, b), 81.0 (a), 80.0 (b), 76.4 (a), 76.3
(b), 76.0 (a), 75.1 (b), 70.4 (b), 70.28 (a), 70.1 (b), 69.7 (a),
69.57 (a), 69.4 (b), 69.3 (b), 69.2 (a) (C-2,3,30,4,40,5,50
from a and C-2,3,30,4,40,5,50 from b), 71.4 (a), 71.2 (aCb),
70.94 (a), 70.91 (b), 70.8 (b), 70.26 (b), 69.51 (a), 62.9 (a),
(C-10,6,60 and 3! –OCH2– from macrocyclic ring from a
and 5! –CH2– from b), 50.0 (NCH2–, b), 49.4 (NCH2–, a),
47.2 (NCH2–, a), 46.5 (NCH2–, b). HRMS: 728.2407
[C30H43O18NNa (MCNa)C requires: 728.2372]. Anal.
Calcd for C30H43O18N: C, 51.06; H, 6.17; N, 1.98. Found:
C, 51.3; H, 6.1; N, 2.0%.
4.4.1. 10,2,3,30,4,40-Hexa-O-acetyl-6,60-O-(3-oxapentan-1,
5-diyl)-sucrose (5b). (Eluent: ethyl acetate). White,
amorphous solid, [a]D C26.8; 1H NMR d: 5.55 (dd,
0
0
0
0
0
J3 ,4 Z7.1 Hz, J4 ,5 Z7.1 Hz, 1H, H-4 ), 5.54 (d, J1,2
Z
3.6 Hz, 1H, H-1), 5.48 (d, 1H, H-30), 5.43 (dd, J3,4Z9.6 Hz,
J2,3Z10.2 Hz, 1H, H-3), 4.93 (dd, J4,5Z10.3 Hz, 1H, H-4),
4.92 (dd, 1H, H-2), 4.40–4.20 (m, 1H, H-5), 04.17–4.13 (m,
1H, H-50), 4.09 (d, JA,BZ11.7 Hz, 1H, H-1 of AB) 4.04–
4.01 (m, 2H, both H-60), 4.00 (d, 1H, second H-10 of AB),
3.73–3.52 (m, 10H, both H-6 and 4!CH2O), 2.24, 2.125,
2.124, 2.11, 2.09, 2.02 (6!s, 6!3H, 6!COCH3). 13C
NMR d: 170.3, 170.2, 170.10, 170.06, 169.86, 169.82 (6!
CO), 102.5 (C-20), 89.5 (C-1), 79.8 (C-50), 76.1 (C-40), 76.0
(C-30), 72.7 (C-60), 72.5 (C-6), 70.44, 70.41, 70.25 (double
intensity, 4!CH2O), 70.22 (C-2), 69.8 (C-3), 69.7 (C-5),
69.5 (C-4), 63.8 (C-10), 20.9, 20.7, 20.65, 20.64, 20.60,
20.56 (6!COCH3). HRMS: 687.2132 [C28H40O18Na (MC
NaC) requires: 687.2107]. Anal. Calcd for C28H40O18: C,
50.60; H, 6.07. Found: C, 50.8; H, 5.9%.
4.4.2. 10,2,3,30,4,40-Hexa-O-acetyl-6,60-O-(5,5-dimethyl-
3,7-dioxanonan-1,9-diyl)-sucrose (10b). (Eluent: hexane/
ethyl acetate, 1:1). Pale yellow oil, [a]D C43.3. IR (film) n
2955, 2872, 1750, 1370, 1224, 1097, 1038 cmK1; 1H NMR
d: 5.66 (d, J1,2Z3.6 Hz, 1H, H-1), 5.47–5.38 (m, 3H, H-3,
H-30, H-40), 5.11 (dd, J3,4Z9.8 Hz, J4,5Z9.8 Hz, 1H, H-4),
4.88 (dd, J2,3Z10.4 Hz, 1H, H-2), 2.19, 2.10, 2.08, 2.06,
2.05, 2.01 (6!s, 6!3H, 6!COCH3), 0.88, 0.86 (2!s, 2!
3H, 2!CH3). 13C NMR d: 170.22, 170.18, 170.02, 169.98,
169.93, 169.62 (6!CO), 103.3 (C-20), 89.5 (C-1), 80.08,
75.7, 74.9, 70.3, 69.9, 69.5 and 69.1 (C-2,3,30,4,40,5,5 ),
76.1, 75.90, 71.2 (double intensity), 71.0, 70.8, 70.6, 69.6,
63.1 (C-1 ,6,60 and 6!–OCH2– from macrocyclic ring),
35.9 (CMe2), 22.3, 22.2 (2!CH3), 20.76, 20.72, 20.65,
20.61, 20.52 (double intensity, 6!COCH3). HRMS:
773.2822 [C33H50O19Na (MCNa)C requires: 773.2839].
Anal. Calcd for C33H50O19: C, 52.80; H, 6.71. Found: C,
53.0; H, 6.5%.
4.4.5. 6,60-Bis-(O-2-hydroxyethyl)-10,2,3,30,4,40-hexa-O-
benzylsucrose (12). Method A. 10,2,3,30,4,40-Hexa-O-
benzylsucrose (4) was converted into the diallyl ether as
described previously17 in 95% yield. Thus, obtained 6,60-
di-O-allyl-10,2,3,30,4,40-hexa-O-benzylsucrose (0.974 g,
1.0 mmol) was dissolved in THF (13 mL) and H2O
(13 mL), to which NaIO4 (1.3 g, 6.0 mmol) was added
followed by OsO4 (70 mL of a w2% solution in toluene).
The resulting mixture was stirred at room temperature for
1.5 h and then partitioned between water (100 mL) and
ether (80 mL). The organic phase was collected, dried,
concentrated and the residue was dissolved in CH2Cl2
(10 mL) and MeOH (10 mL). The solution was cooled to
K78 8C, NaBH4 (0.6 g) was added in several portions, the
mixture was stirred for 1 h at K78 8C, and 2 h at room
temperature. Water (40 mL) was added and product was
extracted with CH2Cl2 (50 mL). The organic layer was
dried, concentrated, and the crude product was purified by
column chromatography (hexane/ethyl acetate, 1:1–2:3) to
afford the title compound 12 (0.508 g, 0.5 mmol, 52%; 49%
overall from 4) as a pale yellow oil, [a]D C44.3. IR (film) n
2916, 2866, 1454, 1086, 1072, 736, 697 cmK1; 1H NMR d:
6.12 (d, J1,2Z4.0 Hz, 1H, H-1). 13C NMR d: 139.2, 138.08,
138.3, 138.2, 137.98, 137.95 (6!Cq benzyl), 103.8 (C-2 ),
87.8 (C-1), 83.4, 802.0, 079.002, 78.95 (double intensity), 77.1
and 70.6 (C-2,3,3 ,4,4 ,5,5 ), 75.2, 74.6, 73.4, 73.1, 73.0,
72.9 (double intensity), 72.3, 71.9 (C-10,6,60, 6!OCH2Ph),
68.49, 68.47, 61.69, 61.66 (4!CH2 from 2-hydroxyethyl).
m/z: 993.5 [M(C58H66O13)CNaC]. Anal: Calcd for
4.4.3. 10,2,3,30,4,40-Hexa-O-acetyl-6,60-O-(1,2-diphenoxy-
3-oxapentylidene)-sucrose (11b). (Eluent: hexane/ethyl
acetate, 1:1). Colorless oil, [a]D C46.6. IR (film) n 2924,
1
2874, 1750, 1371, 1245, 1223, 1040 cmK1; H NMR d:
6.92–6.86 (m, 4H, –C6H4–), 5.66 (d, J1,2Z3.8 Hz, 1H, H-1),
2.2, 2.09, 2.08, 2.05, 2.00, 1.99 (6!s, 6!3H, 6!COCH3).
13C NMR d: 170.16, 170.15, 170.0 (double intensity), 169.9,
169.7 (6!CO), 149.1, 149.0, 121.5 (double intensity),
114.5, 114.4 (aromatic from macrocyclic ring), 103.6
(C-20), 89.7 (C-1), 80.6, 75.9, 75.2, 70.4, 69.94, 69.7 and
69.1 (C-2,3,30,4,40,5,50), 71.5, 71.4, 71.0, 70.9, 70.6, 69.86

S. Jarosz et al. / Tetrahedron 61 (2005) 8485–8492
8491
C58H66O13!1⁄2H2O: C, 71.07; H, 6.89. Found: C, 71.0; H,
7.1%.
–CH2). m/z: 1213.2 [M(C58H64O11I2)CNaC]. Anal. Calcd
for C58H64O11I2C2H2O: C, 56.78; H, 5.26. Found: C, 56.8;
H, 5.5%.
Method B. 10,2,3,30,4,40-Hexa-O-benzylsucrose (0.15 g, 0.
170 mmol) was dissolved in toluene (15 mL), to which a
50% aqueous solution of sodium hydroxide (15 mL) and
tetrabutylammonium bromide (0.01 g, 0.03 mmol) were
added. Then tert-butyl bromoacetate (0.15 mL) was added
dropwise and the mixture was stirred vigorously at room
temperature for 4 h. Water (30 mL) and toluene (15 mL)
were added to the mixture, and the organic layer was
separated, washed with water (10 mL) and brine (10 mL),
dried and concentrated. Purification of the crude product by
column chromatography (hexane/ethyl acetate, 7:1)
4.4.7. 10,2,3,30,4,40-Hexa-O-benzyl-6,60-(3-azabenzyl-
penta-1,5-di-yl)-sucrose (14a). Compound 13 (0.48 g,
0.41 mmol) was dissolved in acetonitrile (25 mL), to
which benzylamine (45 mL, 0.18 mmol) and Na2CO3
(0.15 g) were added. The reaction mixture was stirred
under reflux for 50 h concentrated and the residue was
partitioned between ethyl acetate (50 mL) and water
(50 mL). The organic layer was separated, washed with
water (30 mL), dried, and concentrated, and the product was
isolated by column chromatography (hexane/ethyl acetate,
2:1–1:1) as a pale yellow oil (0.306 g, 0.29 mmol, 73%),
[a]D C28.7. IR (film) n 2921, 2866, 1453, 1091, 1073,
1027, 734, 697 cmK1; 1H NMR d: 5.44 (d, J1,2Z3.3 Hz, 1H,
H-1). 13C NMR d: 139.5, 138.8, 138.7, 138.6, 138.3, 138.00,
137.98 (7!C from benzyl), 104.2 (C-20), 90.1 (C-1)0, 84.09,
83.7, 81.6, 80.01, 71.98, 79.5, and 70.95 (C-2,3,30,4,4 ,5,5 ),
75.4, 74.8, 73.4, 73.2, 72.7, 72.2 (double intensity), 71.7,
71.1, 70.7, 69.1, 60.4, 53.6, 53.2 (C-10,6,60, 7!OCH2Ph
and 4! –CH2–). m/z: 1042.5 [M(C65H71O11N)CNaC].
afforded compound 15 as colorless oil (0.13 g,
Z
1
0.117 mmol, 69%), [a]D C30.7; H NMR d: 5.7 (d, J1,2
3.64 Hz, 1H, H-1), 1.50 (s, 9H, tert-butyl), 1.49 (s, 9H, tert-
Bu). 13C NMR (125 MHz) d: 169.4, 169.2 (2!CO), 139.0,
138.8, 138.4, 138.3, 138.2, 138.0 (6!Cq benzyl), 104.6
(C-20), 90.1 (C-1), 83.8,082.4, 81.9, 79.7 (double intensity),
77.4, 70.6 (C-2,3,30,4,4 ,5,50), 81.3, 81.2 (2!C, Cq tert-
butyl) 75.4, 74.7, 73.4, 72.9, 72.7, 72.5, 72.3, 71.2 (6!
OCH2Ph, 2!CH2COO), 28.1 (6!CH3). m/zZ1133.4
[M(C66H78O15)CNaC]. Anal. Calcd for C66H78O15!
H2O: C, 70.21; H, 7.09. Found: C, 70.2; H, 7.1%.
4.5. Reaction of chalcone with 2-nitropropane catalyzed
by sucrose crown ether analogues†
Compound 15 (0.126 g, 0.114 mmol) was dissolved in dry
THF (45 mL), to which a suspension of LiAlH4 (0.09 g,
2.368 mmol) in THF (15 mL) was added. The mixture was
stirred at room temperature for 3 h and the excess of hydride
was decomposed by careful addition of water. Then it was
partitioned between water (75 mL) and diethyl ether
(60 mL). The layers were separated and the aqueous phase
was extracted with diethyl ether (2!60 mL). The extracts
were combined, washed with water (30 mL), dried and the
solvents were removed in vacuum to give product 14
(0.105 g, 0.108 mmol, 95%; 66% overall from 4) identical
in all respects with the material prepared in Method A.
Chalcone (200 mg, 0.96 mmol), 2-nitropropane (0.2 mL),
and the appropriate crown analogue 5a–10a and 14a
(0.067 mmol) were dissolved in dry toluene (5 mL).
Potassium tert-butoxide (40 mg, 0.37 mmol) was added
and the mixture was stirred at room temperature for 2 days.
Then it was partitioned between water (25 mL) and ethyl
acetate (25 mL), the organic phase was separated, washed
with brine and water, dried and concentrated. The crude
product 17 was isolated by column chromatography
(hexane/ethyl acetate, 9:1). The optical purity of the adduct
17 was determined by comparison of the [a]D value with the
analogous data of the pure enantiomer.18 The results are
shown in Table 3.
4.4.6. 6,60-Bis-(O-2-iodoethyl)-10,2,3,30,4,40-hexa-O-ben-
zylsucrose (13). Compound 12 (0.300 g, 0.31 mmol) was
dissolved in CH2Cl2 (25 mL) containing triethylamine
(3 mL) and DMAP (ca. 7 mg) and cooled to 0 8C. Mesyl
chloride (0.073 mL, 0.9 mmol) was added, the reaction
mixture was stirred for 15 min at 0 8C, 1 h at room
temperature, and then partitioned between water (70 mL)
and CH2Cl2 (100 mL). The organic layer was washed with
water (50 mL), dried, concentrated, and the residue was
dissolved in acetone (25 mL). Sodium iodide (1.3 g,
8.6 mmol) was added and the mixture was stirred under
reflux for 6 h. Acetone was removed under reduced
pressure, and the residue was partitioned between ethyl
acetate (70 mL) and water (70 mL). The organic phase was
washed with water (50 mL), dried, concentrated and the
residue was purified by column chromatography (hexane/
ethyl acetate, 5:1) to give 13 (0.253 g, 0.21 mmol, 69%) as a
References and notes
1. Lichtenthaler, F. W. Carbohydr. Res. 1998, 313, 69–89. an
overview of sucrose chemistry is included in Carbohydrates as
Organic Raw Materials; Lichtenthaler, F. W., Ed.; VCH:
Weinheim, 1991. Descotes, G.; Gagnaire, J.; Bouchu, A.;
Thevenet, S.; Giry-Panaud, N.; Salanski, P.; Belniak, S.;
Wernicke, A.; Porwanski, S.; Queneau, Y. Pol. J. Chem. 1999,
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2. Chan, J. Y. C.; Hough, L.; Richardson, A. C. J. Chem. Soc.,
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Khan, R. Pure Appl. Chem. 1984, 56, 833–844 and references
therein.
brown oil, [a]D C29.2. IR (film) n 2921, 2867, 1454, 1090,
1
1074, 1027, 735, 697 cmK1; H NMR d: 5.71 (d, J1,2
Z
3.6 Hz, 1H, H-1). 13C NMR d: 138.8, 138.7,0138.3, 138.20,
138.17, 137.9 (6!Cq benzyl), 104.7 (C-2 ), 90.2 (C-1),
83.9, 82.3, 81.9, 79.8, 79.6, 77.4 and 70.6 (C-2,3,30,4,
40,5,50), 75.5, 74.9, 73.4, 73.0, 72.47, 72.42, 72.2, 72.0, 71.8,
71.1, and 69.2, 2.78, 2.69 (C-10,6,60, 6!OCH2Ph and 4!
3. Jarosz, S.; Mach, M. Eur. J. Org. Chem. 2002, 769–780 and
references therein.
† The procedure essentially followed the method described in Ref. 18.

8492
S. Jarosz et al. / Tetrahedron 61 (2005) 8485–8492
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¨
Refinement; University of Gottingen, 1997.
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