Synthesis of C6A-to-C6A and C3A-to-C3A diamide linked γ-cyclodextrin dimers

Article abstract of DOI:10.1016/j.tet.2010.02.005

The syntheses of three new diamide-linked γ-cyclodextrin dimers joined by substitution at either a glucopyranose C6^A or C3^A carbon are reported. The syntheses involve the reaction of either C6^A or C3^A amino-substituted γ-cyclodextrin with bis(4-nitrophenyl)succinate to form succinamide linked γ-cyclodextrin dimers or reaction of C6^A azide-substituted γ-cyclodextrin with carbon dioxide to form a urea linked γ-cyclodextrin dimer.

Full text of DOI:10.1016/j.tet.2010.02.005

Tetrahedron 66 (2010) 2895–2898
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A
A
A
A
Synthesis of C6 -to-C6 and C3 -to-C3 diamide linked g-cyclodextrin dimers
Duc-Truc Pham , Huy Tien Ngo , Stephen F. Lincoln , Bruce L. May , Christopher J. Easton b
a
a
a
,
a
*
a
School of Chemistry and Physics, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia
Research School of Chemistry, Australian National University, ACT 0200, Australia
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 July 2009
Received in revised form 4 January 2010
Accepted 1 February 2010
Available online 10 February 2010
The syntheses of three new diamide-linked g-cyclodextrin dimers joined by substitution at either
a glucopyranose C6 or C3 carbon are reported. The syntheses involve the reaction of either C6 or C3A
A
A
A
amino-substituted
clodextrin dimers or reaction of C6 azide-substituted
linked -cyclodextrin dimer.
g
-cyclodextrin with bis(4-nitrophenyl)succinate to form succinamide linked
g
-cy-
A
g
-cyclodextrin with carbon dioxide to form a urea
g
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Gamma-cyclodextrin
Dimer
Synthesis
1. Introduction
2. Results and discussion
Host–guest complexation by native and modified cyclodextrin
CD) hosts often alters the solubility, chemical reactivity and other
properties of the ground and excited states of the guest species and
The modification of native CDs may be achieved through sub-
2
3
6
(
stitution of either a OH , OH or OH (Fig. 1) but their similarity and
number (6, 7 and 8 of each in CD, CD and CD, respectively) ren-
a
b
g
1,2
12
6
is an area of substantial supramolecular chemical interest.
Prominent in such studies are linked CD dimers in which the
ders selective modification challenging. The OH are the most basic
and usually the most nucleophilic, the OH are the most acidic and
the OH are sterically the most difficult to access. Substitution of OH
CD is usually most readily achieved through 6 -O-(4-methyl-
-cyclodextrin, while substitution of OH and
OH is often achieved through 2 -O-(4-methylbenzenesulfonyl)-b-
cyclodextrin. However, using the literature reaction of
4-toluenesulfonylchloride in aqueous solution for
polysubstitution at C6 probably because of the larger gCD annulus.
Larger arenesulfonyl chlorides have been used to achieve mono C6
substitution, buttheyieldsare lowandthecostof thearenesulfonyl
chlorides is greater than that of 4-toluenesulfonylchloride.
2
b
A
A
3
6
linker is substituted onto two
b
CD at either the C6 or C3 carbon of
a glucopyranose unit.3 The nature of the linker can significantly
–9
in
benzenesulfonyl)-
b
A
1
3
2
influence the stabilities of the host–guest complexes formed by the
b
3
A
linked
stantially greater than those expected statistically on the basis of
native CD complex, which is evidence for cooperativity between
the linked
such as adamantane-1-carboxylate and 6-(4-toluidino)naph-
b
CD dimer. In some cases their stability constants are sub-
1
4
b
CD and
1
3
b
gCD results in
3
–6,9
15
b
CD in complexing the guest species.
While guests
3
A
6
16
thalene-2-sulfonate fit the annuli of
b
CD and linked
b
CD dimers
closely, the CD annulus better accommodates larger guest exem-
g
10
11
14
plified by fullerenes and porphyrins. In principle, understanding
of the host–guest complexation of these and other large guests may
A modification of the method of Murakami for the synthesis of
A
2 -O-(4-methylbenzenesulfonyl)-
the simplest and most economical simultaneous route to 2 - and
b
-cyclodextrin was selected as
A
be enhanced through studies of their complexation by linked
gCD
A
dimers. Accordingly, we have synthesised two linked
g
CD dimers
6 -O-(4-methylbenzenesulfonyl)-
yields are modest. The reaction of
chloride in dimethylformamide (DMF) in the presence of dibutyltin
g-cyclodextrin although the
linked through either two C3A or two C6 by succinamide and
A
gCD and 4-toluenesulfonyl-
A
a third
g
CD dimer linked through two C6 by urea (Fig. 1) which to
A
A
the best of our knowledge are the first reported examples of di-
amide-linked CD dimers.
oxide gave a mixture of 2 - and 6 -O-(4-methylbenzenesulfonyl)-
-cyclodextrin (2 CDTs and 6 CDTs), which were readily separated
on a Diaion HP-20 column in 5–10% yields of each.
g
g
g
g
A
A
6
-Azido-6 -deoxy-
described in the literature, through reaction of 6
dium azide in DMF, and 66 CD ur was prepared in 53% yield by
reacting 6 CDN in CO saturated DMF in the presence of
g
-cyclodextrin, (6
g
CDN
3
) was prepared as
16
gCDTs with so-
*
Corresponding author. Tel.: þ61 08 8303 5559; fax: þ61 08 8303 4358.
E-mail address: stephen.lincoln@adelaide.edu.au (S.F. Lincoln).
g
2
g
3
2
0
040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.005

2896
D.-T. Pham et al. / Tetrahedron 66 (2010) 2895–2898
O
O
S
O
A
O
2
A
O
S
OH
6
HO
5
S
OCl
3
2
O
4
O
1
O
O
O
=
+
6
Bu SnO, DMF
2
OH
8
γCD
6γCDTs
2γCDTs
NH HCO ,
4 3
H O
2
NH HCO ,
4 3
NaN3,
DMF
H O
2
A
A
2
6
NH2
A
6 N
3
O
A
3
6
γCDNH2
6γCDN3
23γCDO
CO2,
PPh3
NH OH
4
DMF
H
A
NH2
3
H
6 N
A
A
N 6
4NPS
pyridine
O
3
γCDNH2
H
N
H
N
6
66γCD ur
2
A
A
6
4NPS
pyridine
O
O
H
N
H
N
A
3
A
3
6
6γCD su
2
O
O
where 4NPS = O N
O
O
NO2
2
3
3γCD su
O
O
2
2 2 2
Figure 1. Synthetic routes from gCD to the diamide-linked gCD dimers: 66gCD ur, 33gCD su and 66gCD su.
triphenylphosphine. The preparation of 33
attempted as previous studies show that linking C3 to C3 of two
CDs through the short urea linker is severely inhibited by steric
g
CD
2
ur was not
3. Conclusion
A
A
The preparative methods described herein for 33
2
gCD su,
A
6
crowding of the adjacent CDs and the inversion at C3 in both CDs.
66g
CD su and 66 CD ur are both facile and economic such that
2
g
2
6
,17
Bis-4-nitrophenyl succinate
required in the preparation of
multigram quantities may be prepared. The preparative method-
ology for the first two are potentially applicable to a range linked
3
3g
CD su and 66 CD su was synthesised by reaction of succinyl
2
g
2
chloride with 4-nitrophenol in a similar manner to that described
in the literature.
g-cyclodextrin dimers of varying diamide linker length. The
products are chemically stable with no degradation observed in
A
A
ꢀ
The first step in the synthesis of previously unreported (2 S,3 S)-
samples stored at ꢁ5 to 0 C for several years. In aqueous solution
3A-amino-3 -deoxy-
A
g
g
-cyclodextrin (3
CDTs with aqueous ammonium bicarbonate to
give 2 ,3 -manno-epoxide- -cyclodextrin (23 CDO), which was
g
CDNH
)
was achieved
the diamide linkers are stable over a wide pH range.
2
through reaction of 2
In preliminary complexation studies 600 MHz 2D 1H NOESY
A
A
ꢁ3
ꢁ3
g
g
NMR spectra of 10 mol dm sodium 6-(4-toluidino)naph-
isolated through chromatography on Diaion HP-20 and BioRex 70
thalenesulfonate, NaTNS, and either equimolar 66
g
CD
2
ur,
þ
ꢀ
(
H ) in 78.6% yield. The product was then reacted with ammonium
33gCD
2
su, or 66
g
CD
2
su in D
2
O at pD 7.0 and 25 C reveal strong
3
ꢀ
3,5,6
hydroxide (25%, 60 cm ) at 60 C for 4 h to give 3
g
CDNH
2
after
cross-peaks arising from dipolar interactions between the H
þ
13
chromatographic separation on BioRex 70 (H ) in 56.7% yield. C and
protons of the linked
TNS consistent with complexation of this guest by the diamide-
g
CD annuli and the aromatic protons of
1
A
A
ꢁ
H NMR spectra indicate that the C2 and C3 carbons of a glycopyr-
anose unit in CD moiety are inverted to form an altropyranose ring
during the synthesis, as is also the case for 3
g
linked gCD dimers. Quantitative studies of the complexation the
1
8,19
b
CDNH
) was converted from
CDTs by treatment with ammonium hydroxide over five days and
2
.
The new
substantially larger porphyrins and also of complexation in
A
A
20
6
6
-amino-6 -deoxy-
g
-cyclodextrin (6
gCDNH
2
hydrophobe substituted poly(acrylate)s are in progress.
g
þ
was isolated through chromatographyon BioRex 70 (H ) in 18% yield.
The 33 CD su and 66 CD su linked CD dimers were syn-
4. Experimental
g
2
g
2
g
thesised through a general method with yields of 75.7 and 91.6%,
respectively. The succinate diester was stirred with 2.5 equiv of
4.1. General
either 3
perature to give 33
g
CDNH
2
or 6
g
CDNH
su and 66
2
in pyridine for 48 h at room tem-
CD su, which were separated on
Proton and 13C NMR spectra were recorded with a Varian
1
gCD
2
g
2
Gemini ACP-300 spectrometer operating at 300.145 MHz ( H) or
þ
13
1
Biorex 70 (H ).
75.4 MHz ( C). 2D H NOESY NMR spectra were recorded with

D.-T. Pham et al. / Tetrahedron 66 (2010) 2895–2898
2897
3
a Varian-Inova 600 spectrometer operating at 599.957 MHz using
a standard pulse sequence with a mixing time of 0.3 s. Thin layer
chromatography (TLC) was carried out on Merck Kieselgel 60 F254
on aluminium-backed sheets. For analysis of cyclodextrin de-
rivatives, plates were developed with 7:7:5:4 v/v ethyl acetate/
propan-2-ol/ammonium hydroxide/water and the compounds
were visualised by drying the plate and then dipping it into a 1%
sulfuric acid in ethanol solution and heating it with a heat-gun. To
visualise amino bearing cyclodextrins plates were dried prior to
dipping into 0.5% ninhydrin in ethanol and heated with a heat-gun,
before dipping in 1% sulfuric acid in ethanol. For the preparations
The crude 6gCDTs was dissolved in water (500–700 cm ) and
loaded onto a Diaion HP-20 column (3ꢂ25 cm). After flushing with
3
water (ca. 1 dm ), followed by 10–20% aqueous methanol solvent
gradient elution of unreacted gCD, 6gCDTs was eluted with 30–40%
aqueous methanol (ca. 250 cm fractions). The fractions containing
the product were combined and evaporated to dryness under vac-
3
uum to give 6
g
CDTs as a white powder. Yield: 2.47 g (4.25%). TLC:
1
R
c
¼1.40. H NMR, (DMSO-d ): 7.78, 7.46 (ABq, J¼8.3 Hz, 4H, ArH),
d
H
6
2
3
6.05–5.35 (m, 16H, OH , OH ), 5.09–4.81 (m, 8H, H1), 4.31–3.20 (m,
6
13
55H, H2-6, OH ), 2.42 (s, 3H, Ar–CH
3
). C NMR,
d
C
(DMSO-d
6
): 133.2,
A
130.7, 128.8, 126.2 (Ar–C); 102.9–101.8 (C1 ); 81.6–80.8 (C4); 73.6–
described below R
c
represents the R
f
of a substituted cyclodextrin
3
69.7 (C2, C3, C5); 60.7 (C6); 40.9–38.4 (DMSO); 21.8 (Ar–CH ).
relative to the R of the parent cyclodextrin, R
points were measured using a Kofler hot-stage apparatus viewed
through a Reichert microscope and are uncorrected. As cyclodex-
f
f
(
g
CD)¼0.42. Melting
A
A
4.2.2. 2 ,3 -Manno-epoxide-
g
-cyclodextrin, 23
gCDO. A solution of
A
2 -O-(4-methylbenzenesulfonyl)- -cyclodextrin (4 g, 2.76 mmol)
in aqueous ammonium bicarbonate (10%, 125 cm ) was stirred at
60 C for 3 h. The solvent was removed under vacuum and the
residue was redissolved in water, followed by evaporation to dry-
ness (this procedure was repeated three times). This crude product
was dissolved in water (20 cm ) and added drop-wise to vigorously
stirred acetone (500 cm ). The precipitate formed was collected by
filtration and washed with acetone and diethylether to give 4 g of
crude product. The crude material was dissolved in water (125 cm )
g
ꢀ
3
trin derivatives decompose without melting above 180 C, melting
ꢀ
points were not determined. Elemental analyses were performed
by the Microanalytical Service of the Chemistry Department, Uni-
versity of Otago, Dunedin, New Zealand. Mass spectrometry was
carried on a Micromass Q-TOF2 instrument. Samples were dis-
solved in HPLC grade methanol, Milli-Q water or a mixture of the
3
3
ꢁ3
two at a concentration of 0.5 mg cm
.
3
Bio-Rex 70 resin was purchased from Bio-Rad Laboratories, Inc,
CA and converted to the acid form using 3 mol dm hydrochloric
ꢁ
3
and loaded onto a Diaion HP-20 column (3ꢂ20 cm). The column
0
3
acid.
g-Cyclodextrin (Nihon Shokuhin Kako Co.), N,N -dicyclohex-
was washed with water (1 dm ) and 10% aqueous methanol and the
ylcarbodiimide (DCC) (Merck), 4-toluenesulfonylchloride (Aldrich)
and 4-nitrophenol (BDH) were used without further purification.
All other reagents and solvents were of good quality reagent grade.
washings were evaporated under vacuum to give the product as
a white powder, which contained traces of 2
g
CDNH
2
by-product.
column
A
A
The pure 2 ,3 -manno-epoxide was run through
a
A
A
16
þ
6
-Azido-6 -deoxy-
g-cyclodextrin and bis-4-nitrophenyl succi-
(4.5ꢂ4.5 cm) of BioRex 70 (H ), 100–200 mesh (BioRad) to remove
6
,17
nate
were prepared by literature methods.
2g
2
CDNH . The fractions containing the product were combined and
evaporated to dryness under vacuum to give as a white powder.
1
Yield: 2.77 g (78.6%). TLC: R
c
¼1.15. H NMR,
H 2
d (D O): 5.27 (s, 1H,
A
4
.2. Synthesis
H1 -epoxide), 5.13–5.07 (m, 7H, H1), 3.95–3.59 (m, 47H, H2-6),
.49 (d, 1H, H2 -epoxide). C NMR, d (D O): 104.5–103.7 (C1),
C 2
83.7–83.0 (C4), 75.7–72.1 (C2 , C3 , C5), 63.6 (C6 ), 62.9
A
13
3
A
B–H
B–H
B–H
4
.2.1. 2 -O-(4-Methylbenzenesulfonyl)-
g
-cyclodextrin, 2
g
CDTs and
A
A
A
A
its 6 - analogue, 6
added to anhydrous DMF (150 cm ) and the mixture was stirred for
two hours at 0 C under dry nitrogen until dissolution was com-
plete. After heating to 100 C, dibutyltin oxide (25.1 g, 100.9 mmol)
g
CDTs.
g
-Cyclodextrin (51.9 g, 40.0 mmol) was
(C6 ), 57.1 (C2 ), 52.2 (C3 ).
3
ꢀ
A
A
A
A
4 . 2 . 3 . 3 - A m i n o - 3 - d e o x y- ( 2 S , 3 S ) -
g
- c yc l o d e x t r i n ,
ꢀ
A
A
3gCDNH . 2 ,3 -Mannoepoxide-g-cyclodextrin (2.6 g, 2.03 mmol)
was dissolved in aqueous ammonium hydroxide (25%, 60 cm ) and
the solution was stirred at 60 C for 4 h. The mixture was then
2
3
was added and stirred for another 2 h. The mixture was then cooled
ꢀ
ꢀ
to 0 C, triethylamine (12.2 g, 120.6 mmol) was added, followed by
dropwise addition of 4-toluenesulfonylchloride (20 g, 105 mmol) in
DMF (50 cm ). The mixture was stirred for 2 h before another
evaporated to dryness and the residual was dissolved in aqueous
3
3
ammonium hydroxide (28%, 20 cm ) and added to acetone
3
portion of 4-toluenesulfonylchloride (9.7 g, 50.9 mmol) in DMF
(500 cm ). The precipitate was collected, washed with acetone and
3
(
20 cm ) was added dropwise. The resultant solution was stirred for
diethylether and dried under vacuum to obtain 2.74 g of the crude
3
a further 10 h at room temperature and then concentrated to
product. This was dissolved in water (20 cm ) and loaded onto
3
þ
a yellow syrup. This was added to 2 dm of vigorously stirred ace-
a column (4.5ꢂ4.5 cm) of BioRex 70 (H ), 100–200 mesh (BioRad).
3
tone and stirring was continued for 30 min. The precipitate formed
was collected by filtration, washed with acetone and diethylether
and dried under vacuum to give 62 g of crude product, which was
recrystallised from ca. 200 ml water. The precipitate was collected
After flushing with water (ca. 500 cm ), the 3
gCDNH
2
product was
ꢁ3
eluted with 1 mol dm
aqueous ammonium hydroxide (ca.
3
100 cm fractions). Fractions containing the product were com-
bined and evaporated to dryness under vacuum (removal of excess
ammonia was achieved by dissolving the residue in water and
and dried under vacuum to give ca. 9 g of crude 6
filtrate was evaporated to dryness to give ca. 47 g of crude 2
g
CDTs, while the
CDTs.
CDTs was dissolved in water (1 dm ) and loaded
onto a Diaion HP-20 column (5ꢂ30 cm). After flushing with ca.
g
evaporating to dryness three times) to afford 3
g
CDNH
2
as a white
(D O): 5.22
(d, 2H, H1 ), 5.16–4.93 (m, 6H, H1), 4.20 (m, 1H, H2 ), 4.00–3.56 (m,
3
1
The crude 2
g
powder. Yield: 1.49 g (56.7%). TLC: R
c
¼0.76. H NMR,
d
H
2
A
A
3
A
13
3
dm of water, followed by 10–15% aqueous methanol solvent
46H, H2-6), 3.10 (d, 1H, H3 ). C NMR,
d
C
(D
2
O): 103.1–99.7 (C1),
B–H
A
gradient elution of unreacted CD, 2 CDTs was eluted with 20–25%
g
g
80.9–80.2 (C4), 79.2–71.1 (C2, C3 , C5), 60.8–59.8 (C6), 52.2 (C3 ).
3
aqueous methanol (ca. 400 cm fractions). The fractions containing
the product were combined, the methanol was removed and the
A
A
A
4.2.4. 6 -Amino-6 -deoxy-cyclodextrin, 6
2
gCDNH . 6 -O-(4-Methyl-
product was dried under vacuum to give the 2
g
CDTs as a white
benzenesulfonyl)- -cyclodextrin, 6 CDTs (3.4 g, 2.3 mmol) was
g
g
1
3
ꢀ
powder. Yield: 4.37 g (7.5%). TLC: R
c
¼1.67. H NMR (DMSO-d ):
d
H
6
3
dissolved in ammonium hydroxide (28%, 250 cm ) at 0 C. The re-
action vessel was closed and left in the dark with occasional stirring
for five days. The ammonium hydroxide was removed under re-
2
7
4
CH
.83, 7.47 (ABq, J¼8.2 Hz, 4H, ArH), 5.91–5.69 (m, 15H, OH , OH ),
6
.88 (s, 8H, H1), 4.30–3.30 (m, 56H, H2-6, OH ), 2.41 (s, 3H, Ar–
1
3
3
3
). C NMR,
d
C
(DMSO-d
6
): 133.4, 129.9, 128.2, 125.7 (Ar–C);
duced pressure, after which water was added (100 cm ) and re-
B–H
A
101.9–101.1 (C1 ), 97.3 (C1 ); 82.3–78.2 (C4); 73.1–69.2 (C2, C3,
moved under reduced pressure. The remaining solid was dissolved
3
C5); 60.2 (C6); 40.9–38.4 (DMSO); 21.3 (Ar–CH ).
3
in ammonium hydroxide (28%, 20 cm ) and the solution added

2898
D.-T. Pham et al. / Tetrahedron 66 (2010) 2895–2898
3
A
drop-wise to vigorously stirring acetone (450 cm ) and stirred for
3
74.4, 74.9, 74.9, 75.2, 75.6 (C2,3,5), 62.4, 62.9 (C6), 53.6 (C3 ), 33.6
2
þ
0 min. The resulting precipitate was dried under vacuum to give
as a cream powder. This was dissolved in water
20 cm ) and loaded onto a BioRex 70 (H ) column. The column was
(CH
2
). Mass spectrum m/z: 1359.9 (MþNa) . Elemental analysis:
crude 6
(
gCDNH
2
C
100
H
164
N
2
O
80$19H
2
O: C, 39.81; H, 6.75; N, 0.93. Found: C, 39.54; H,
3
þ
6.39; N, 0.89.
3
washed with water (400 cm ), and the title compound was eluted
ꢁ
3
0
A
A
with
4ꢂ100 cm fractions). The 6
evaporated to dryness under reduced pressure, and the residue
freeze dried to give 6 CDNH as a white solid. Yield: 0.55 g (18%).
(D O) 5.37 (s, 2H, H1 ), 5.10 (m,14H, H1 ),
0.05–0.1 mol dm
aqueous
ammonium
carbonate
4.3.2. N,N -Bis(6 -deoxy-
g
-cyclodextrin-6 -yl)
succinamide,
3
(
g
CDNH
2
containing fractions were
66
g
CD
2
su. The title compound was prepared by treatment of the
(1.58 g, 1.21 mmol) with bis(4-nitrophenyl) succinate
(176 mg, 0.49 mmol). After the general work-up and purification
6gCDNH
2
g
d
2
1
A
B–H
TLC: R
c
¼0.90. H NMR,
.93–3.58 (m, 48H, H2-6). C NMR,
0.50–79.0 (C4); 73.89–71.88 (C2, C3, C5); 60.33 (C6); 41.05 (C6 ).
2
procedure, the title compound was obtained as a white solid. Yield:
1
3
1
3
8
d(D
2
O): 103.72–101.77 (C1);
1.2 g (91.6%). TLC: R
c
¼0.45. H NMR,
H 2
d (D O): 5.11 (m, 16H, H1),
A
13
3.42–3.93 (m, 96H, H2-H6), 2.59 (m, 4H, CH2). C NMR,
C 2
d (D O):
1
77.5 (C]O), 104.3 (C1), 85.7, 83.1 (C4), 75.6, 75.0, 74.4, 72.8
0
A
A
ur. 6A-
B–H
A
4
.2.5. N,N -Bis(6 -deoxy-
g
-cyclodextrin-6 -yl)urea, 66
-cyclodextrin (1 g, 0.75 mmol) was dissolved in
DMF (20 cm ) and the solution was saturated with dry CO and
stirred at room temperature for 15 min. Triphenylphosphine
g
CD
2
(C2,3,5), 62.9 (C6 ), 42.8 (C6 ), 33.7 (CH
2
). Mass spectrum m/z:
80$20H O: C,
A
2þ
Azido-6 -deoxy-
g
1359.9 (MþNa) . Elemental analysis: C100
H
164
N
2
O
2
3
2
39.58; H, 6.78; N, 0.92. Found: C, 39.48; H, 6.40; N, 0.91.
3
(
297 mg, 1.134 mmol) in DMF (5 cm ) was added dropwise and the
reaction mixture was saturated with CO and stirred for 27 h after
Acknowledgements
2
which it was added drop-wise to vigorously stirred acetone. The
resulting precipitate was collected by centrifugation, washed ace-
tone and diethylether, dried under vacuum and freeze dried. Yield:
The support of this study by the Australian Research Council and
the University of Adelaide is gratefully acknowledged.
1
5
20 mg (53%). TLC: R
c
¼0.40. H NMR,
d
H
(D
(D
04.5 (C1), 85.5–83.0 (C4), 76.4–73 (C2, C3, C5), 63.0 (C6 ), 43.2
2
O): 5.09–5.07 (m, 16H,
Supplementary data
1
2
6
13
H ); 3.9–3.3 (m, 96H, H -H ). C NMR:
d
C
2
O) 163.1 (amide C]O),
B–H
1
(
C
Supplementary 1D 1H and 13C NMR and 2D 1H NOESY NMR
spectra may be found, in the online version, at doi:10.1016/
j.tet.2010.02.005.
A
2þ
C6 ). Mass spectrum m/z: 1332.8 (MþNa) . Elemental analysis:
97
160
H N
2
O
79$21H O: C, 38.8; H, 6.7; N, 1.0. Found: C, 38.6; H, 6.4;
2
N, 1.2.
References and notes
4
.3. General procedure for the preparation of the
succinamide linked CD dimers
g
1. Easton, C. J.; Lincoln, S. F. Modified Cyclodextrins: Scaffolds and Templates for
Supramolecular Chemistry; IPC: London, 1999.
2. Wenz, G.; Han, B.-H.; MUller, A. Chem. Rev. 2006, 106, 782–817.
3. Breslow, R.; Greenspoon, N.; Guo, T.; Zarzycki, R. J. Am. Chem. Soc. 1989, 111,
A
A
A
A
-cyclodextrin or 6A-
¨
Either (2 S,3 S)-3 -amino-3 -deoxy-
g
A
amino-6 -deoxy-
pyridine (20 cm ) and stirred at room temperature for 15 min. Bis-
-nitrophenyl succinate (0.4 equiv) was added to this solution in
two or more portions over a period of 1 h. The reaction mixture was
then stirred for 48 h at room temperature before being added
dropwise to diethylether (200 cm ) with vigorous stirring. The re-
g-cyclodextrin (w1 mmol) was dissolved in
8296–8297.
3
4
. Haskard, C. A.; Easton, C. J.; May, B. L.; Lincoln, S. F. J. Phys. Chem. 1996, 100,
14457–14461.
. Liu, Y.; Yang, Y.-W.; Yang, E.-C.; Guan, X.-D. J. Org. Chem. 2004, 69, 6590–6602.
. Pham, D.-T.; Clements, P.; Easton, C. J.; Papageorgiou, J.; May, B. L.; Lincoln, S. F.
New J. Chem. 2008, 32, 712–718.
4
5
6
3
7. Mourer, M.; Hapiot, F.; Monflier, E.; Menuel, S. Tetrahedron 2008, 64, 7159–7163.
8
9
. Casas-Solvas, J. M.; Martos-Maldonato, M. C.; Vargas-Berenguel, A. Tetrahedron
008, 64, 10919–10923.
sultant precipitate was collected by centrifugation, washed with
acetone and diethylether and dried under vacuum. The product was
2
. Pham, D.-T.; Clements, P.; Easton, C. J.; Papageorgiou, J.; May, B. L.; Lincoln, S. F.
Supramol. Chem. 2009, 21, 510–519.
þ
dissolved in H
2
O and run down a BioRex 70 (H ) column to remove
A
A
A
A
A
1
0. Cataldo, F. Polym. Degrad. Stab. 2002, 77, 111–120.
11. Hamai, S. Supramol. Chem. 2004, 16, 113–120.
2. Khan, A. R.; Forgo, P.; Stine, K. J.; D’Souza, V. T. Chem. Rev. 1998, 98, 1977–1996.
13. Brady, B.; Lynam, N.; O’Sullivan, T.; Ahern, C.; Darcy, R. Org. Synth. 2000, 77,
20–224.
4. Murakami, T.; Harata, K.; Morimoto, S. Tetrahedron Lett. 1987, 28, 312–314.
5. Djedaini-Pilard, F.; Azaroual-Bellanger, N.; Gosnat, M.; Vernet, D.; Perly, B.
either excess (2 S,3 S)-3 -amino-3 -deoxy-
amino-6 -deoxy-
obtained by freeze drying followed by further drying over phos-
phorous pentoxide.
g
-cyclodextrin or 6 -
A
g-cyclodextrin. The white solid products were
1
2
1
1
0
A
A
A
A
4
.3.1. N,N -Bis((2 S,3 S)-3 -deoxy-
mide, 33 CD su. The title compound was prepared by treatment of
the 3 CDNH (1.39 g, 1.08 mmol) with bis(4-nitrophenyl) succinate
155 mg, 0.43 mmol). After the general work-up and purification
procedure, the title compound was obtained as a white solid. Yield:
.87 g (75.7%). TLC: R
H1), 4.26–3.59 (m, 96H, H2-6), 2.6 (s, 4H, CH2). C NMR,
77.7 (C]O), 105.8, 104.2, 102.3 (C ), 81.9, 82.7, 83.1 (C4), 72.3, 73.9,
g
-cyclodextrin-3 -yl)
succina-
J. Chem. Soc., Perkin Trans. 2 1995, 723–730.
16. Palin, R.; Grove, S. J. A.; Prosser, A. B.; Zhang, M.-Q. Tetrahedron Lett. 2001, 42,
g
2
8897–8899.
g
2
1
7. Easton, C. J.; v. Eyk, S. J.; Lincoln, S. F.; May, B. L.; Papageorgiou, J.; Williams, M. L.
Aust. J. Chem. 1997, 50, 9–12.
18. Jiang, T.; Sukumaran, D. K.; Soni, S.-D.; Lawrence, D. S. J. Org. Chem. 1994, 59,
(
1
5149–5155.
0
c
¼0.60. H NMR,
H 2
d (D O): 5.39–4.94 (m, 16H,
1
2
9. Murakami, T.; Harata, K.; Morimoto, S. Chem. Lett. 1988, 553–556.
0. Guo, X.; Abdala, A. A.; May, B. L.; Lincoln, S. F.; Khan, S. A.; Prud’homme, R. K.
Polymer 2006, 42, 2976–2983.
13
C 2
d (D O):
1
1