Synthesis of 6I-amino-6I-deoxy-2I-VII,3I-VII-tetradeca-O-methyl-cyclomaltoheptaose.

Article abstract of DOI:10.1016/j.carres.2004.03.007

The preparation of 6(I)-amino-6(I)-deoxy-2(I-VII),3(I-VII)-tetradeca-O-methyl-cyclomaltoheptaose is reported. Two different routes (A and B), both starting from beta-cyclodextrin (betaCD), have been examined. Route A involved: (i) synthesis of heptakis(6-

Full text of DOI:10.1016/j.carres.2004.03.007

Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 1361–1366
Note
Synthesis of 6I-amino-6I-deoxy-2I–VII,3I–VII-tetradeca-O-methyl-
cyclomaltoheptaose
Tommaso Carofiglio,a,* Matteo Cordioli,a Roberto Fornasier,a Laszlo Jicsinszkyb and
Umberto Tonellatoa
aDipartimento di Scienze Chimiche, and ITM-CNR (sezione di Padova), Universitꢀa di Padova,Via Marzolo 1, 35131 Padova, Italy
bCyclolab R&D Laboratory, Illatos ꢁut 7, H-1097 Hungary
Received 8 December 2003; received in revised form 27 February 2004; accepted 3 March 2004
Available online 15 April 2004
Abstract—The preparation of 6I-amino-6I-deoxy-2I–VII,3I–VII-tetradeca-O-methyl-cyclomaltoheptaose is reported. Two different
routes (A and B), both starting from b-cyclodextrin (bCD), have been examined. Route A involved: (i) synthesis of heptakis(6-O-
tert-butyldimethylsilyl)-bCD from bCD; (ii) permethylation of the secondary hydroxyl groups with methyl iodide and sodium
hydride; (iii) desilylation of the primary hydroxyls with ammonium fluoride; (iv) monotosylation at O-6 position of per-(2,3-O-
methyl)-bCD; (5) nucleophilic replacement of the tosyl group with azide anion; (v) reduction of the azido group by catalytic transfer
hydrogenation using hydrazine hydrate in the presence of Pd/C in methanol/water. Route B started from the known 6I-monoazido-
6I-monodeoxy-b-CD (two steps from b-CD) and entailed: (i) protection of the remaining primary hydroxyls using tert-butyldi-
methylsilylchloride (TBDMSCl); (ii) exhaustive methylation of the secondary hydroxyls with methyl iodide and sodium hydride; (iii)
removal of the TBDMS protecting groups with ammonium fluoride; (iv) reduction of the azido group as above. Route A was found
to be less convenient than Route B due to the inherent difficulty of controlling the monotosylation of per-(2,3-O-methyl)-bCD.
ꢀ 2004 Published by Elsevier Ltd.
Keywords: Methylated cyclodextrin; Selective tosylation; Aminodeoxycyclodextrin
Cyclodextrins (cyclomaltooligosaccharides, CDs) are
water-soluble cyclic oligosaccharides composed, for the
most common representatives, of six (a-), seven (b-), or
or site-specific delivery of drugs.4a;b Furthermore, being
chiral entities, CDs have a significant potential for
asymmetric synthesis and chiral separations. Finally,
attachment of properly functionalized CDs to solid
surfaces, may lead to useful organic–metal composites.
With this latter objective in mind, we have recently
reported the synthesis of a permethylated b-CD deriv-
ative bearing a lipoic acid unit linked via an amide bond
(TRIMEB-LA), which gives strong chemisorption on
colloidal gold allowing the realization of nanoparticles
coated with hundreds of cyclodextrin moieties.5 For the
synthesis of TRIMEB-LA, we exploited the precursor
6I-amino-6I-deoxy-2I–VII,3I–VII-6II–VII-decaosa-O-methyl-
cyclomaltoheptaose (TRIMEB-NH2), which can be
conveniently prepared in a multigram scale starting
from bCD using a four steps route recently reported by
Jicsinszky and Ivanyi.6 TRIMEB-NH2 is a key com-
pound that makes simpler the synthesis of cyclodextrin
eight (c-) a-(1 fi 4)-linked
D-glucopyranose units ar-
ranged in a torus-shaped structure with hydrophilic
exterior and a comparatively hydrophobic cavity. As a
consequence of these structural features, CDs show the
remarkable capacity to form host–guest inclusion com-
plexes in aqueous solution with hydrophobic molecules
of the proper size and shape.1 Combining the cyclo-
dextrin molecular recognition ability with proper func-
tional groups is of significance2a in several research fields
and applications aimed at realizing models for enzyme
binding pockets,2b optical sensors of organic molecules
in aqueous environment,3 and systems for slow release
* Corresponding author. Tel.: +39-468275670; fax: +39-598275239;
e-mail: tomasso.carofiglio@uuipd.it
0008-6215/$ - see front matter ꢀ 2004 Published by Elsevier Ltd.
doi:10.1016/j.carres.2004.03.007

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T. Carofiglio et al. / Carbohydrate Research 339 (2004) 1361–1366
conjugates for at least two reasons: (i) TRIMEB-NH2
has only one reactive amino group, which can be cou-
pled by standard peptide chemistry protocols to mole-
cules containing a carboxyl functionality, without
requiring any protection/deprotection step; (ii) the
lipophilic nature of the permethylated cyclodextrin
moiety, produces bCD conjugates soluble not only in
water but also in common organic solvents and that
makes straightforward their purification by standard
flash column chromatography on silica gel. This latter
point is of crucial importance for applications in which
pure cyclodextrin derivatives rather than mixtures of
positional isomers or homologous derivatives are nee-
ded.
OH
OTBDMS
O
OTBDMS
O
i)
ii)
O
O
O
O
OH
HO
OMe
MeO
OH
HO
7
7
7
1
2
3
iii)
OH
OTs
OH
iv)
O
O
O
O
O
O
MeO
OMe
MeO
OMe
MeO
OMe
6
7
4
5
Although the synthesis and purification of TRIMEB-
LA and other derivatives of TRIMEB-NH2 bearing an
appended chromophore or fluorophore proved to be
easy, their use as molecular sensors or supramolecular
receptors was rather disappointing. In fact, we consis-
tently found that the pendant group is so strongly self-
included into the cavity or into a counter molecule that
the cyclodextrin cavity is almost unavailable for binding
of any target substrate. In order to capitalize upon the
ease of purification of derivatives like TRIMEB-LA (or
similar compounds), we addressed 6I-amino-6I-deoxy-
2I–VII,3I–VII-tetradeca-O-methyl-cyclomaltoheptaose 10,
as an attractive substitute of TRIMEB-NH2, despite the
predictable synthetic difficulties. As a matter of fact, its
preparation involves two of the most challenging syn-
thetic problems in the chemical modification of cyclo-
dextrins: (i) monosubstitution at the 6-position and; (ii)
exclusive peralkylation at the 2- and 3-positions.
Although there are some well-established methods
that might provide a solution to the above problems one
at a time,7a;b the reactivity of the primary hydroxyl
groups in substitution reactions, when all secondary
hydroxyls are alkylated, was never confronted. So, we
envisaged the synthetic plan indicated as Route A in
Scheme 1. It involves the preparation of per-2,3-O-me-
thyl-bCD (4),10b followed by introduction of the amino
group.
Scheme 1. Route A: (i) TBDMSCl, pyridine; (ii) NaH/CH3I, THF;
(iii) NH4F, MeOH; (iv) TsCl, 5:1 CH2Cl2–pyridine.
tallization from various solvent mixtures, without puri-
fication by column chromatography on silica gel. The
8
identity of the product was confirmed by 1H NM R and
by ESIMS. Heptakis(6-O-tert-butyldimethylsilyl-2,3-di-
O-methyl)cyclomaltoheptaose (3) was obtained from 2
in 86% yield by exhaustive methylation of the secondary
hydroxyl groups with a large excess of NaH/iodome-
thane in dry THF at room temperature. Further desil-
ylation of 3 was accomplished with ammonium fluoride
hydrogen fluoride in methanol under reflux.
By analogy with the reported preparations of 6I-ami-
no-6I-deoxy-bCD via the corresponding 6I-O-tosyl
derivative,6;9a–c tosylation of 4 was attempted in 5:1
CH2Cl2–pyridine. However, TLC monitoring of the
reaction mixture showed that 5 was formed together with
a considerable amount of polytosylated derivatives.
Extensive purification by flash chromatography allowed
to obtain compound 5 in 21% yield and its identity was
established by 1H NMR spectroscopy and ESIMS.
Changes in the tosyl chloride/cyclodextrin ratio did not
lead to any improvement of the O-6 monotosylation.
Alternative tosylation methods reported in the litera-
ture7a;9 were also pursued but considerable amounts of
ditosylated derivatives were always obtained. Moreover,
purification of 5 was successful only in a 100 mg scale by
column chromatography and failed for any larger
amounts. For this reason, this route was abandoned to
follow the alternative one depicted in Scheme 2 (Route B).
Compound 6 was obtained in two steps from bCD by
selective monotosylation at O-6 (33% yield) followed by
nucleophilic displacement of the tosyl group with a 20%
molar excess of sodium azide in DMF at 105–110 °C
(quantitative), following literature procedures.6 The
basic idea behind Route B was to relegate the tosylation
step to the very beginning of the synthesis where a low
yield is more acceptable since it only involves a loss of
the commercially available bCD. Treatment of 6 with
TBDMSCl in dry pyridine afforded the cyclodextrin
In order to synthesize 4, all the primary hydroxyl
groups of bCD were protected by reaction with
TBDMSCl in dry pyridine.8;10a;b Kinetic studies revealed
that one-portion addition of TBDMSCl results in more
efficient control on the substitution range. Using low
temperature is necessary only at the starting period of
the reaction. Application of the higher reaction tem-
perature makes the purification procedure easier due to
the reduced amounts of the lower silylated products.
10a
€
These modifications of Fugedi
and Takeo et al.10b
resulted in an easily crystallizable crude product. Prep-
aration of the corresponding a- and c-cyclodextrin by
this modified method also did not require chromato-
graphy. The desired per-(6-O-tert-butyldimethylsilyl)-
bCD (2) was obtained in good yield (>75%) by recrys-

T. Carofiglio et al. / Carbohydrate Research 339 (2004) 1361–1366
1363
OH
OTBDMS
O
N3
N3
i)
O
O
O
O
O
O
HO
O
OH
OH
HO
HO
OH
OH
HO
6
6
6
7
ii)
OH
N3
OTBDMS
O
N3
iii)
O
O
O
O
O
MeO
O
O
OMe
MeO
OMe
OMe
MeO
OMe
MeO
6
6
8
9
iv)
OH
NH2
O
O
O
O
OMe
MeO
OMe
MeO
6
10
Scheme 2. Route B: (i) TBDMSCl, dry pyridine; (ii) NaH/MeI, DMF; (iii) NH4F, MeOH; (iv) hydrazine hydrate/Pd/C.
derivative 7 (70% isolated yield), in which all the pri-
mary hydroxyl groups were silylated. The 1HNMR
spectrum of 7 in CDCl3 was consistent with the pro-
posed structure. Furthermore, the corresponding
ESIMS spectrum in the presence of NH4Cl as cationiz-
ing agent gave the expected signal at m=z 939 ([7 þ 2
(NH4)]2þ). Permethylation of the remaining secondary
hydroxyl groups of 7 by a large excess of methyl iodide
and sodium hydride in dry DMF gave 8 in 88% isolated
yield. Desilylation of 8 was carried out as above de-
scribed for 4 and resulted in compound 9 (63% yield).
Finally, reduction of the azido group of 9 by catalytic
transfer hydrogenation using hydrazine hydrate in the
presence of Pd/C in water gave the desired cyclodextrin
derivative 10 in 90% yield. Then, the overall yield for the
target compound 10 from commercial bCD was 11.5%.
lizer). Pyridine was stored on molecular sieves. TLC
plates (E. Merck 5554 F254) were developed in saturated
chamber on 10 cm; spots were visualized by UV 254 nm
and charring of H2SO4–EtOH sprayed plates at 110 °C.
1.2. Heptakis(6-O-tert-butyldimethylsilyl)cyclomaltohep-
taose (2)
Freshly dried bCD (22.7 g, 0.020 mol) was dissolved in
dry pyridine (230 mL) at room temperature. Then,
TBDMSCl (24.1 g, 0.160 mol) was added in one portion
with external water bath cooling. The reaction mixture
was stirred for 4.5 h at room temperature. When the
reaction did not show any change in the desired product
by TLC (40:10:1 CHCl3–MeOH–water) the reaction
mixture was poured onto water (2.5 L). The precipitate
formed was collected by filtration, washed with water
(2 · 200 mL) and acetone (200 mL). The crude product
(35.7 g) was recrystallized twice from CH2Cl2 (50 mL)
and MeOH (350 mL) and once from CH2Cl2 (25 mL)
and acetone (200 mL). The obtained product (17.6 g,
46% yield) was suitable for further reactions (>95%
purity). A second crop of crystals (12.1 g, 32% yield) was
obtained from mother liquors after several recrystal-
1. Experimental
1.1. Reagents
b-Cyclodextrin was a Wacker product, and all other
reagents were purchased from Fluka and used as
supplied. 6I-O-p-Tolylsulfonylcyclomaltoheptaose, 6I-
azido-6I-deoxy-cyclomaltoheptaose (6), and heptakis(6-
O-tert-butyldimethylsilyl)cyclomaltoheptaose are also
commercial products and can be obtained from Cyclo-
lab R&D Lab. (Budapest, Hungary). Chloroform for
TLC was distilled before use to remove EtOH (stabi-
lizations (total yield 29.7 g, 78%): mp 304–308 °C (ace-
25
tone), lit.10a 314–318 °C, lit.10b 299–302 °C, ½aŠ þ 105:3
D
(c 2, CHCl3), lit.10a þ105°, lit.10b þ113° (at 22 °C); RF
0.45–0.46 (40:10:1 CHCl3–MeOH–water); ESIMS (1:1
water–MeOH): m=z 983.5 ([(2) þ 2 NH4]2þ, calcd 984.0),
993.3 ([(2) þ 2 NH4 þ H2O]2þ, calcd 993.0).

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T. Carofiglio et al. / Carbohydrate Research 339 (2004) 1361–1366
1.3. Heptakis(6-O-tert-butyldimethylsilyl-2,3-di-O-
methyl)cyclomaltoheptaose (3)
was added dropwise within ꢀ10 min. The reaction was
monitored by TLC (50:10:1 CHCl3–MeOH–water).
After 24 h, some starting material was still present to-
gether with the expected product and some polytosyl-
ated derivatives. In the attempt to increase the yield,
more tosyl chloride (0.36 g, 0.019 mol) in CH2Cl2
(15 mL) was added. After 5 h, the solvents were removed
by evaporation and the solid residue was purified by
column chromatography (silica gel, 9:1 fi 4:1 CHCl3–
Compound 2 (29.0 g, 0.015 mol) was dissolved in per-
oxide-free THF (290 mL), then NaH was added (7.2 g,
0.30 mol, dispersed in oil, 80%). The reaction mixture
was heated up to 40 °C and iodomethane (42.6 g,
18.6 mL, 0.30 mol) was added in 3 mL portions within a
15–30 min period. After 30 min stirring at 40 °C, more
sodium hydride (1.8 g, 0.075 mol) and iodomethane
(10.7 g, 4.7 mL, 0.075 mol) in two portions were added
and the reaction mixture was further stirred overnight at
room temperature.
The excess of sodium hydride and iodomethane was
decomposed by addition of MeOH (50 mL). Volatile
compounds were removed by evaporation under dimin-
ished pressure resulting in a sticky solid, which was sus-
pended in n-hexane (320 mL). The solid was filtered off
and discarded. The solvent was removed in a rotatory
evaporator under diminished pressure yielding a yellow
oil (34 g), which contained some oil from sodium hydride.
Removal of the oil could be achieved at this point by
filtration through a silica gel bed, or after the desilylation
MeOH); yield: 1.2 g (21%): mp 194–195 °C [dec]
25
(amorphous); ½aŠ þ151 (c 1, CHCl3); RF 0.32–0.33
D
(50:10:1 CHCl3–MeOH–water); 1H NMR (250 MHz,
CDCl3): d 7.79 (d, 2H, H-20,60), 7.36 (d, 2H, H-30,50),
5.13 (m, 7H, H-1), 4.46 (m, 6H, OH-6), 3.98–3.46 (m, 77
H), 3.17 (m, 7H), 2.44 (s, 3H, CH3–Ar); ESIMS (1:1
water–MeOH): m=z 759.0 ([(5) þ 2 NH4]2þ, calcd 760.0);
1501.1 ([(5) þ 2 NH4]2þ, calcd 1502). Anal. Calcd for
C63H104O37S: C, 50.94; H, 7.06; S, 2.16. Found: C, 51.11;
H, 7.11; S, 2.01.
1.6. 6I-Azido-6I-deoxy-hexakis(6-O-tert-butyldimethyl-
silyl)cyclomaltoheptaose (7)
step, but due to technical reasons the latter is recom-
Dried 6I-azido-6I-deoxycyclomaltoheptaose6 (23.2 g,
0.02 mol) was dissolved in pyridine (230 mL) at room
temperature and immersed in a cold-water bath. tert-
Butyldimethylsilyl chloride (21.1 g, 0.14 mol) was added
and the reaction mixture was allowed to warm up to
room temperature (26 °C) and further stirred for 9 h.
When no more change was observed by TLC (40:10:1
CHCl3–MeOH–water), the reaction mixture was poured
onto water (2 L) and allowed to stand for crystallization
overnight. The waxy crystals were filtered off and wa-
shed with water (3 · 100 mL), then after changing the
collector, with acetone (2 · 50 mL). The resulting white
crystalline material (32.5 g) contained some pyridine and
smelled TBDMSOH. A second crop of crude product
was obtained by evaporation of the acetone solution
(6.2 g, strong TBDMSOH smell). Recrystallization from
1:3 CH2Cl2–acetone (25 mL) gave a material, which was
practically identical to the first crystalline product
(3.1 g). The two crude crops were combined (35.6 g,
96.5%) and recrystallized twice from 1:3 CH2Cl2–ace-
tone (144 mL and 100 mL, respectively). The resulting
product (23.5 g, 63%) had purity higher than 95% and it
was suitable for further reactions. A second portion of
the product could be obtained from the concentrated
mother liquors of recrystallization after a short-column
chromatography (silica gel, 100 g, elution with CH2Cl2)
and recrystallization from MeOH and 1:3 CH2Cl2 and
25
D
mended: ½aŠ þ 130:6 (c 2, CHCl3), lit.10b þ97° (at 26 °C);
RF 0.91–0.93 (50:25:1 CHCl3–MeOH–water); ESIMS
(1:1 water–MeOH): m=z 1081.9 ([(3) þ 2 NH4]2þ, calcd
1082.0); 1108.4 ([(3) þ 2 NH4 þ 3H2O]2þ, calcd 1109.0).
1.4. Heptakis(2,3-di-O-methyl)cyclomaltoheptaose (4)
To compound 3 (34 g, 0.015 mol, which contained about
2 g of oil, were added MeOH (340 mL), and ammonium
fluoride (20 g, 0.35 mol). The oily material slowly dis-
solved at reflux; the desilylation was completed after 5 h
reflux as confirmed by TLC (40:10:1 CHCl3–MeOH–
water). MeOH was removed by evaporation and the
crude product was dissolved in CH2Cl2, and filtered
through an aluminum oxide bed (60 g, diam 70 mm,
height 17 mm), to obtain 4 (17.0 g, 85%), which is oil-
free: mp 160–166 °C (amorphous), lit.10b: 168–172 °C;
25
½aŠ þ 155:3 (c 2, CHCl3), lit.10b þ176° (at 24 °C); RF
D
0.42–0.43 (50:25:1 CHCl3–MeOH–water); 1H NM R
(250 MHz, Me2SO-d6): d 5.12 (m, 7H, H-1), 4.54 (m, 7H,
OH-6) 3.75–3.29 (m, 77H, H-2, H-3, H-4, H-5, H-6a, H-
6b, Me-2, Me-3); ESIMS (1:1 water–MeOH): m=z 681.9
([(4) þ 2 NH4]2þ, calcd 683.0); 1347 ([(4) þ NH4]þ, calcd
1348). Anal. Calcd for C56H98O35: C, 50.52; H, 7.42.
Found: C, 50.6; H, 7.46.
1.5. Heptakis(2,3-di-O-methyl)-6I-O-p-tolylsulfonyl-
cyclomaltoheptaose (5)
acetone (6.3 g, 17%, 80% combined yield): mp 266–
25
270 °C [dec] (acetone), ½aŠ þ105:9 (c 1, CHCl3); RF
D
0.41–0.45 (50:25:1 CHCl3–MeOH–water); 1H NM R
(250 MHz, CDCl3): d 6.70 (m, 7H, OH-2), 5.22 (m, 7H,
OH-3) 4.90 (m, 7H, H-1), 4.06–3.36 (m, 42H, H-2, H-3,
H-4, H-5, H-6a, H-6b), 0.87 (m, 54H, CH3–CMe2–Si),
Compound 4 (5.0 g, 0.038 mol) was solubilized in
CH2Cl2 (50 mL) and pyridine (10 mL) and p-toluene-
sulfonyl chloride (0.82 g, 0.043 mol) in CH2Cl2 (50 mL)

T. Carofiglio et al. / Carbohydrate Research 339 (2004) 1361–1366
1365
0.04 (m, 36H, Me2–Si); ESIMS (1:1 water–MeOH): m=z
939.1 ([(7) þ 2 NH4]2þ, calcd 939.5). Anal. Calcd for
C78H153N3O34Si6: C, 50.76; H, 8.36; N, 2.28. Found: C,
50.71; H, 8.45; N, 2.35.
water–MeOH): m=z 694.4 ([(9) þ 2 NH4]2þ, calcd 695.5).
Anal. Calcd for C56H97N3O34: C, 49.59; H, 7.21; N, 3.10.
Found: C, 49.77; H, 7.27; N, 3.14.
1.9. 6I-Amino-6I-deoxy-heptakis(2,3-di-O-methyl)cy-
clomaltoheptaose (10)
1.7. 6I-Azido-6I-deoxy-heptakis(2,3-di-O-methyl)-hexa-
kis(6II–-O-tert-butyldimethylsilyl)cyclomaltoheptaose (8)
Compound 9 (2.50 g, 0.0018 mol) was dissolved in water
(45 mL). The solution was bubbled with nitrogen then
Pd (10%) supported on carbon (0.35 g) was added. After
10 min, hydrogen was applied to the reaction and kept
under stirring at room temperature. The reaction was
monitored by TLC (40:10:1 CHCl3–MeOH–water).
After 18 h, the solution was filtered then, removal of
Acetone and CH2Cl2 free compound 7 (18.5 g, 0.01 mol)
was dissolved in dry and peroxide-free THF (185 mL)
and NaH was added (4.8 g, 0.20 mol, dispersed in oil
80%) then the reaction mixture was heated up to 40 °C
and iodomethane (42.6 g, 18.6 mL, 0.20 mol) was added
in 3 mL portions. After 30 min stirring at ꢀ40 °C, more
NaH (1.8 g, 0.075 mol) and iodomethane (10.7 g, 4.7 mL,
0.075 mol) were added. The reaction mixture was stirred
for an additional hour at ꢀ40 °C, then heated up to
reflux and stirred for an additional hour. The reaction
mixture was cooled and the excess of NaH was
decomposed with MeOH (50 mL) then volatile com-
pounds were removed by distillation. To the sticky solid,
n-heptane (420 mL) was added and the solid was filtered
off. Removal of the solvent resulted in a dense, yellow oil
(22.8 g). Removal of oil (from NaH) could be done at
this point (by filtration through a silica gel bed) or after
the desilylation step. Our experiences suggested that
solvent resulted in a white solid; yield 2.20 g (90%): mp
25
244–247 °C [dec]; ½aŠ þ151 (c 1, CHCl3); RF 0.32
D
(40:10:1 CHCl3–MeOH–water); 1H NMR (250 MHz,
CDCl3): d 7.79 (d, 2H, H-20,60), 7.36 (d, 2H, H-30,50),
5.13 (m, 7H, H-1), 4.46 (m, 6H, OH-6), 3.98–3.46 (m,
77H), 3.17 (m, 7H, H-2-5, H-6ab, Me-2, Me-3), 2.44 (s,
3H, Me–Ar); ESIMS (1:1 water–MeOH): m=z 759.0
([(10) þ 2 NH4]2þ, calcd 760.0); 1501.1 ([(10) þ 2 NH4]2þ
,
calcd 1502). Anal. Calcd for C56H99NO34: C, 50.56; H,
7.50; N, 1.05. Found: C, 50.61; H, 7.57; N, 1.03.
Compound 10 was converted into its hydrochloride
by addition of aq 0.01 MHCl to its water solution, and
purification of the desilylated product is easier: mp
freeze-dried to prevent carbonatation: mp 228–233 °C
25
D
25
144–150 °C (amorphous); ½aŠ þ135:4 (c 1, CHCl3);
[dec] (amorphous); ½aŠ þ149 (c 1, water). Anal. Calcd
D
1
RF 0.87–0.89 (50:25:1 CHCl3–MeOH–water); H NM R
for C56H100ClNO34: C, 49.21; H, 7.37; N, 1.02, Cl 2.59.
Found: C, 49.32; H, 7.41; N, 1.05; Cl, 2.44.
(250 MHz, CDCl3): d 5.22–5.08 (m, 7H, H-1), 4.17–4.05
(m, 7H), 3.76–3.50 (m, 70H), 3.11–3.03 (m, 7H), 0.87 (m,
54H, tert-butyl-Si), 0.04 (m, 36H, Me2–Si); ESIMS (1:1
water–MeOH): m=z 1036.7 ([(8) þ 2 NH4]2þ, calcd
1037.5). Anal. Calcd for C92H181O34N3Si6: C, 54.11; H,
8.93, N, 2.06. Found: C, 54.04; H, 8.87; N, 2.12.
Acknowledgements
This work was partly supported by Hungarian Research
Fund (OTKA-T37802) and by the Italian Ministry of
the University and Scientific Research (MURST)
(‘Supramolecular Devices’ national project).
1.8. 6I-Azido-6I-deoxy-heptakis(2,3-di-O-methyl)cyclo-
maltoheptaose (9)
Compound 8 (14.26 g, 0.007 mol) was suspended in
MeOH (250 mL) and stirred until complete solubiliza-
tion. Then, NH4F (10.44 g, 0.242 mol) was added and
the mixture was refluxed. The outcome of the reaction
was monitored by TLC (40:10:1 CHCl3–MeOH–water).
After 18 h, the reaction was completed. The solvent was
distilled off and the residue was solubilized in CH2Cl2
(200 mL) and extracted with brine (3 · 1 L). The organic
layer was dried over MgSO4, filtered and the solvent was
evaporated in a rotatory evaporator obtaining a residue,
which was purified by column chromatography (silica
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