Synthesis of novel highly water-soluble 2:1 cyclodextrin/fullerene conjugates involving the secondary rim of β-cyclodextrin

Article abstract of DOI:10.1016/j.tet.2004.10.015

Two novel fullerene[60]-cyclodextrin conjugates have been prepared, they display the highest solubility in water reported to date. This is the first synthesis of such conjugates in which the linker is attached to the secondary rim of β-CD. Graphical Abstr

Full text of DOI:10.1016/j.tet.2004.10.015

Tetrahedron 60 (2004) 12163–12168
Synthesis of novel highly water-soluble 2:1 cyclodextrin/fullerene
conjugates involving the secondary rim of b-cyclodextrin
a
Juan Yang, Yali Wang, Andre Rassat, Yongmin Zhang and Pierre Sinay
a
b
a,
a
*
´
¨
a
´ ´ ´
Ecole Normale Superieure, Departement de Chimie, UMR 8642: CNRS-ENS-Universite Pierre-et-Marie-Curie,
24 rue Lhomond, 75231 Paris Cedex 05, France
Ecole Normale Superieure, Departement de Chimie, UMR 8640: CNRS-ENS-Universite Pierre-et-Marie-Curie,
24 rue Lhomond, 75231 Paris Cedex 05, France
b
´
´
´
Received 11 August 2004; revised 6 October 2004; accepted 7 October 2004
Available online 28 October 2004
Abstract—Two novel fullerene[60]-cyclodextrin conjugates have been prepared, they display the highest solubility in water reported to
date. This is the first synthesis of such conjugates in which the linker is attached to the secondary rim of b-CD.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Since cyclodextrins and permethylcyclodextrins are not
toxic, these molecules seem well adapted to study the
application to biological problems of the very attractive
photo-, electro-chemical and physical properties of fuller-
enes.3–5 It was postulated that these conjugates could be
present in water equilibria between conformers such as A, B
and C (Fig. 2); A and B could form micelle-like aggregates,
while C could exist as a non-associated species.1
The recently described 2:1 cyclodextrin–fullerene conju-
gates 1 (Fig. 1)1,2 display high solubility in water, an
adequate property for their use in biological systems.3
As expected, these compounds were very soluble in water:
UV and NMR spectra showed the presence of aggregates;
and the ‘internal complexation’ conformer C was not
detected. Although this high solubility is convenient for
application to biological systems, micellar aggregation may
inducechemical,6–9 electrochemical10,11 orphotophysical12,13
properties differing from those of the isolated fullerene
molecule (see however14). It thus seems worthwhile to try
new structural modifications in order to obtain cyclodex-
trin–fullerene conjugates that would be highly water-soluble
Figure 1. The 2:1 CD-C60 conjugates linked via the primary rim of the b- or
g-CD.
Figure 2. Postulated equilibria of the CD-C60 conjugates in water.
Keywords: C60; Conjugate; Cyclodextrin; Fullerene; Synthesis.
* Corresponding author. Tel.: C33 1 44323335; fax: C33 1 44323397; e-mail: yongmin.zhang@ens.fr
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.10.015

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J. Yang et al. / Tetrahedron 60 (2004) 12163–12168
and, even at the highest concentration, would exist mainly in
the form of the internal complex.
to the cyclodextrin through the larger secondary rim, in
order to favour a conformation D of the internal complex
similar to the one (E) found by calculations on the (g-CD)-
fullerene 2:1 complex18 (Fig. 3).
Because of the much easier availability of the primary
carbon derivatives,15 the two moieties of all the cyclodex-
trin–fullerene conjugates reported so far,1,2,16,17 are linked
via the primary external rim of the b- or g-CD. As suggested
previously,1,2 a possible way to favour internal complexa-
tion vs. micelle formation could be to connect the fullerene
We present here two examples of fullerene–cyclodextrin
conjugates in which the linker is attached to the secondary
rim. This is indeed the first preparation of such conjugates
through what may be a general method. In order to allow
flexibility, we have chosen two long linkers consisting of 24
and 14 atoms, respectively. Permethylated b-cyclodextrin
(PMBCD) 2 was selected for a better solubility in water
compared to the native b-CD.
2. Results and discussion
The key intermediate of this synthesis is a methylated b-CD
3 having specifically located hydroxyl groups available on
the secondary rim. The traditional methods for selectively
Figure 3. CD-C60 conjugate D and g-CD/C60 2:1 complex E.
Scheme 1. Reagents and conditions: (i) DIBAL, 0 8C, 18 h (56%); (ii) NaN3, DMF, 80 8C, 15 h (94%); (iii) TsCl, Et3N, CH2Cl2, rt, 24 h (94%); (iv) NaH,
DMF, 80 8C, 15 h (71%); (v) Ac2O, Py, 40 8C, 15 h (68%); (vi) MeI, NaH, THF, 66 8C, 5 h (70%); (vii) HS(CH2)3SH, Et3N, MeOH, rt, 28 h (95%).

J. Yang et al. / Tetrahedron 60 (2004) 12163–12168
12165
Scheme 2. Reagents and conditions: (i) Et3N, CH2Cl2, rt, 7 h (84%); (ii) C60, CBr4, DBU, toluene, rt, 24 h (29%).
modified methylated CDs proceeds usually through a
temporary regioselective protection of specific hydroxyl
groups of the native CD, followed by O-methylation and
final removal of the protective groups to unmask the
required hydroxyl functions. We recently introduced a
conceptually new way to obtain directly such com-
pounds.19–21 This alternative approach is based on the
efficient selective de-O-alkylation of a fully alkylated a or
b-CD, using commercially available diisobutylaluminum
isomer. The structure of compound 6 was confirmed from
the 1H NMR spectrum of derivative 7, readily obtained from
6 by acetylation; the H-3 of the glucose unit B displayed a
deshielded signal at 5.41 ppm (dd, J2,3ZJ3,4Z10.0 Hz),
indicating that alkylation of 6 took place at position 2. The
remaining OH of compound 6 was then methylated to give
azidoalkyl permethylated b-CD 8, which, after treatment
by propane dithiol in the presence of triethyl amine,23 gave
aminoalkyl b-CD derivative 9 in 95% yield.
hydride (DIBAL-H) as
‘scalpel’.22
a regioselective chemical
Condensation of 9 with malonic ester diacylchloride 101
gave compound 11, which through the Hirsch–Bingel
reaction24 with C60 afforded, after 24 h at room temperature,
the target compound 12, identified as a methanofullerene
mono-adduct (Scheme 2).
Thus (Scheme 1) b-CD A2,B3-diol 3 was regioselectively
prepared from the commercially available permethylated
b-CD in 56% yield, and condensed with azidotosylate 5,
obtained from bromoundecanol through azidoalcohol 4, to
afford azidoalkyl b-CD 6 in good yield and as a single
The second conjugate was prepared in a slightly modified
Scheme 3. Reagents and conditions: (i) TFA, CH2Cl2, rt, 4 h; then (COCl)2, CH2Cl2, reflux, 21 h. (ii) Et3N, CH2Cl2, rt, 18 h (70%).

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J. Yang et al. / Tetrahedron 60 (2004) 12163–12168
way: aminocyclodextrin 9 was reacted with the fullerene
diacylchoride 14, prepared from 131 in the presence of
triethylamine, to give conjugate 15 in 70% yield (Scheme 3).
Flash column chromatography was performed on silica gel
60 (230–400 mesh, E. Merck).
4.1.1. 11-Azido-1-undecanol (4). A mixture of the 11-
bromo-1-undecanol (100 mg, 0.40 mmol), NaN3 (78 mg,
1.20 mmol) in dry DMF (3 mL) was stirred at 80 8C
overnight under argon. The DMF was removed by
evaporation under reduced pressure, the residue was
dissolved in CH2Cl2, washed with water and dried over
MgSO4. After evaporation of solvent, the residue was
purified by chromatography on silica gel, eluted by CH2Cl2
to give the compound 4 as a yellowish syrup (80 mg, 94%).
RfZ0.39 (CH2Cl2/MeOH 50:1); 1H NMR (250 MHz,
CDCl3): d 3.61 (t, JZ6.5 Hz, 2H, CH2O), 3.25 (t, JZ
6.9 Hz, 2H, CH2N3), 2.12 (s, 1H, OH), 1.61–1.28 (m,
18H, 9!CH2); 13C NMR (100 MHz, CDCl3): d 62.83
(CH2–OH), 51.45 (CH2–N3), 32.73, 29.54, 29.44, 29.40,
29.12, 28.81, 26.68, 25.74 (9C, 9!CH2); MS (ESI): m/z
235.8 (100%, MCNaC); Anal. Calcd for C11H23ON3: C,
61.92; H, 10.89; N, 19.70. Found: C, 61.79; H, 10.84; N,
19.86.
The conjugates 12 and 15 are very soluble in dichloro-
methane and in chloroform and have a very high solubility
in water at 20 8C, greater than 7!10K2 M for 12 and 9!
10K2 M for 15: clear solutions were obtained after
dissolving 12 (32 mg) in water (100 mL), and 15 (35 mg)
in water (100 mL). To our knowledge, these are the highest
solubilities in neutral water for fullerene derivatives.4,25
As for the previously reported CD-C60 conjugates, aggre-
gates are present in water solutions: the NMR spectra of
12 and 15 are much broader in water than in chloroform.
The UV spectra of dichloromethane solutions of 12 and 15
are not distinguishable from those of 1c. In water solution,
these three compounds have slightly different UV spectra;
none of these spectra display the absorption peak at 430 nm
observed in dichloromethane solutions, a critical indication
of the presence of aggregates.26–28
Similarly, water solutions (concentrations 10K4–10K5 M)
of these conjugates did not show any circular dichroism in
the absorption bands of C60, although induced circular
dichroism has been observed for a g-CD/C60 complex.29,30
4.1.2. 11-Azido-1-undecanyl tosylate (5). To a solution of
4 (194 mg, 0.91 mmol), TsCl (262 mg, 1.37 mmol) in dry
CH2Cl2 (4 mL) was added triethylamine (0.4 mL,
2.73 mmol) under argon, the reaction mixture was stirred
at room temperature for 24 h. After diluted with CH2Cl2,
washed with brine, water, dried over MgSO4 and evapo-
rated, the residue was purified by flash-chromatography,
eluting with 1:1 cyclohexane/CH2Cl2 to offer 5 as a
colourless syrup (313 mg, 94%): RfZ0.39 (cyclohexane/
3. Conclusion
We have reported here the first preparation of CD-C60
conjugates in which the connection is achieved through the
secondary rim of the CD. These molecules display the
highest solubility in water reported to date. Like most water-
soluble fullerenes derivatives31 (see however25) these
conjugates are aggregated in water solution. Since it is
possible that the affinity of b-CD for the fullerene moiety is
not sufficient to induce this type of complexation, work is
in progress towards conjugates connected to g-CD, now2
through the secondary rim.
1
CH2Cl2 1:2); H NMR (250 MHz, CDCl3): d 7.79 (d, 2H,
0
Ja,bZ8.3 Hz, 2!Ph-H2,2 ), 7.35 (d, 2H, Ja,bZ8.1 Hz, 2!
0
Ph-H3,3 ), 4.02 (t, JZ6.5 Hz, 2H, CH2O), 3.26 (t, JZ6.9 Hz,
2H, CH2N3), 2.45(s, 3H, Ph-CH3), 1.69–1.23 (m, 18H, 9!
CH2); 13C NMR (100 MHz, CDCl3): d 144.47 (Ph-C1),
0
0
132.95 (Ph-C4), 129.62 (Ph-C2,2 ), 127.64 (Ph-C3,3 ), 70.51
(CH2–OH), 51.22 (CH2–N3), 29.18, 29.13, 29.11, 28.89,
28.66, 28.61, 28.57, 26.47, 25.09 (9C, 9!CH2), 21.39 (Ph-
CH3); MS (ESI): m/z 390.0 (100%, MCNaC); Anal. Calcd
for C18H29O3N3S: C, 58.81; H, 7.97; N, 11.43. Found: C,
58.73; H, 7.99; N, 11.30.
4. Experimental
4.1.3. Azidoalkyl b-CD (6). A mixture of 3 (423 mg,
0.30 mmol), NaH (60%, 18 mg, 0.45 mmol) in dry DMF
(5 mL) under argon was stirred at room temperature for 1 h.
Compound 5 (133 mg, 0.36 mmol) was dissolved with dry
DMF (2 mL) and added to the above mixture at room
temperature, then the reaction mixture was stirred at 80 8C
overnight. MeOH was added dropwise to quench the
reaction and the solvent was removed by evaporation.
After dissolved with CH2Cl2, washed with brine and water,
dried over MgSO4 and concentrated, the crude product was
purified by column chromatography (cyclohexane/acetone
3:2) to afford 6 (342 mg, 71%) as a white amorphous solid:
RfZ0.36 (cyclohexane/acetone 3:2); [a]DZC132 (c 1.65,
CHCl3); 1H NMR (400 MHz, CDCl3): d 5.16–5.12 (m, 4H,
4.1. General procedures
Optical rotations were measured at 20G2 8C with a Perkin
Elmer Model 241 digital polarimeter, using a 10 cm, 1 mL
cell. Chemical Ionisation Mass Spectra (CI-MS ammonia)
and Fast Atom Bombardment Mass Spectra (FAB-MS)
were obtained with a JMS-700 spectrometer. Elemental
analyses were performed by Service de Microanalyse de
´
l’Universite Pierre et Marie Curie, 4 Place Jussieu, 75005
Paris, France. NMR spectra were recorded on a Bruker
Avance 250 spectrometer or a Bruker DRX 400 spectro-
meter at ambient temperature. 1H NMR chemical shifts are
referenced to residual protic solvent (CDCl3, dHZ7.30) or
the internal standard TMS (dHZ0.00). 13C NMR chemical
shifts are referenced to the solvent signal (dcZ77.0 for the
central line of CDCl3). Reactions were monitored by thin-
layer chromatography (TLC) on a pre-coated silica gel 60
F254 plate (layer thickness 0.2 mm; E. Merck, Darmstadt,
Germany) and detection by charring with sulphuric acid.
4!H1), 5.11 (d, 1H, J1,2Z3.6 Hz, H1), 5.08 (d, 1H, J1,2
Z
3.6 Hz, H1), 4.97 (d, 1H, J1,2Z3.6 Hz, H1); 13C NMR
(100 MHz, CDCl3): d 101.19, 99.77, 99.68, 99.32, 98.99,
98.85, 98.76 (7C, 7!C1), 83.32, 82.29, 82.19, 82.03, 81.97,
81.69, 81.64, 81.61, 81.59, 81.47, 81.45, 81.25, 81.19,
80.79, 80.36, 80.21, 80.09, 70.96, 70.91, 70.87, 70.82, 69.99

J. Yang et al. / Tetrahedron 60 (2004) 12163–12168
12167
(28C, 7!C2, C3, C4, C5), 72.98, 71.40, 71.36, 71.30, 71.10
(8C, CH2OC7!C6), 61.81, 61.61, 61.48, 61.41, 61.38,
61.36, 59.00, 58.94, 58.91, 58.90, 58.56, 58.52, 58.49,
58.46, 58.41, 58.35 (19C, 19!OMe), 51.41 (CH2N3),
29.60, 29.47, 29.39, 29.37, 29.26, 29.06, 28.76, 26.64,
25.64 (9C, 9!CH2); MS (FAB): m/z 1618.8 (75%, MC
NaC); Anal. Calcd for C72H129O35N3: C, 54.16; H, 8.14; N,
2.63. Found: C, 54.40; H, 8.42; N, 2.56.
undecyl) acid (122 mg, 0.24 mmol) in dry CH2Cl2 (5 mL) in
ice-bath under argon was added oxalyl chloride (0.063 mL,
0.73 mmol). The mixture was stirred under reflux for 18 h.
After the solvent was removed in vacuum, the compound 10
(135 mg, dark blue solid) was obtained and used without
further purification.
4.1.7. Permethylated b-CD dimer (11). To a solution of 9
(360 mg, 0.23 mmol) in dry CH2Cl2 (12 mL) in ice-bath
under argon were added triethylamine (79 mL, 0.57 mmol)
and 10 (61 mg, 0.11 mmol, dissolved with 3 mL CH2Cl2).
The mixture was stirred at room temperature for 7 h. After
removal of the solvent, the residue was flash chromato-
graphed, eluting with 8:1 ethyl acetate/MeOH to provide 11
(343 mg, 84%) as a white amorphous solid. RfZ0.52
(EtOAc/isopropanol/H2O 6:3:1); [a]DZC121 (c 1.2,
4.1.4. Azidoalkyl permethylated b-CD (8). A mixture of 6
(90 mg, 0.056 mmol), NaH (60%, 11.3 mg, 0.28 mmol) in
dry THF (2 mL) under argon was stirred at room
temperature for 1 h. After CH3I (17.5 mL, 0.28 mmol)
added, the reaction mixture was stirred at 66 8C for 5 h,
MeOH was added dropwise to quench the reaction and the
solvent was removed by evaporation. The residue dissolved
with CH2Cl2, washed with brine, water, dried (MgSO4),
concentrated, and purified by flash-chromatographed (elu-
ent: cyclohexane/acetone 2:1) to give 8 (63 mg, 70%) as a
white amorphous solid: RfZ0.42 (cyclohexane/acetone
1
CHCl3); H NMR (400 MHz, CDCl3): d 5.53 (t, 2H, JZ
5.5 Hz, 2!NH), 5.19–5.16 (m, 8H, 8!H1), 5.14 (2d, 4H,
J1,2Z3.6 Hz, 4!H1), 5.08 (d, 2H, J1,2Z3.4 Hz, 2!H1),
4.15 (t, 4H, JZ6.8 Hz, 2!CH2OOC); 13C NMR (100 MHz,
CDCl3): d 172.96, 166.62 (4C, 2!CO–NH, 2!CO–O),
98.90, 98.86, 98.84, 98.82, 98.80 (14C, 14!C1), 82.00,
81.91, 81.88, 81.75, 81.72, 81.65, 81.61, 81.58, 81.47,
80.84, 80.38, 80.34, 80.11, 80.08, 79.99, 79.89, 79.78,
70.98, 70.85, 70.79, 70.71 (56C, 14!C2,C3,C4,C5), 71.47,
71.39, 71.31, 71.23, 71.21, 71.13, 66.42, 65.57 (18C, 2!
OCH2, 2!CH2OCO, 14!C6), 61.59, 61.46, 61.34, 61.31,
61.29, 58.91, 58.87, 58.59, 58.56, 58.46, 58.36, 58.30 (40C,
40!OMe), 41.62, 39.42, 36.81 (5C, OOC–CH2–COO, 2!
CH2–NH–CO, 2!CH2–CO–NH), 29.97, 29.61, 29.54,
29.50, 29.48, 29.43, 29.41, 29.36, 29.27, 29.24, 29.10,
28.35, 26.86, 25.89, 25.74, 25.68 (36C, 36!CH2); MS
(FAB): m/z 3655.6 (100%, MCNaC); Anal. Calcd for
C173H310O76N2$H2O: C, 56.88; H, 8.63; N, 0.77. Found: C,
56.66; H, 8.51; N, 0.91.
1
3:2); [a]DZC122 (c 2.45, CHCl3); H NMR (400 MHz,
CDCl3): d 5.19–5.16 (m, 4H, 4!H1), 5.14 (2d, 2H, J1,2
Z
3.5 Hz, 2!H1), 5.08 (d, 1H, J1,2Z3.4 Hz, H1); 13C NMR
(100 MHz, CDCl3): d 98.94, 98.93, 98.89, 98.86, 98.83 (7C,
7!C1), 82.03, 81.95, 81.92, 81.77, 81.75, 81.68, 81.64,
81.61, 81.50, 80.86, 80.41, 80.36, 80.12, 80.02, 79.94,
79.81, 71.00, 70.87, 70.82, 70.74 (28C, 7!C2,C3,C4,C5),
71.49, 71.42, 71.35, 71.26, 71.16 (8C, CH2OC7!C6),
61.61, 61.49, 61.37, 61.34, 61.31, 58.93, 58.91, 58.90,
58.62, 58.58, 58.48, 58.39, 58.33 (20C, 20!OMe), 51.41
(1C, CH2N3), 30.09, 30.00, 29.53, 29.43, 29.41, 29.08,
28.76, 26.65, 25.90 (9C, 9!CH2); MS (FAB): m/z 1632.9
(100%, MCNaC); Anal. Calcd for C73H131O35N3$H2O: C,
53.81; H, 8.25; N, 2.58. Found: C, 53.83; H, 8.40; N, 2.24.
4.1.5. Aminoalkyl permethylated b-CD (9). To a solution
of 8 (285 mg, 0.18 mmol) in dry MeOH (8 mL) were added
1,3-propanedithiol (0.8 mL) and triethylamine (0.8 mL)
under argon, the mixture was stirred at room temperature
for 28 h. A white precipitate was formed. After filtration and
washing with MeOH, the filtrate was concentrated. The
residue was flash chromatographed, eluting with 6:1 ethyl
acetate/MeOH, then 3:3:2 ethyl acetate/isopropanol/H2O
to afford 9 (265 mg, 95%) as a white amorphous solid:
RfZ0.43 (ethyl acetate/isopropanol/H2O 3:3:2); [a]DZC
4.1.8. 2:1 b-Cyclodextrin/fullerene[60] conjugate (12).
To a solution of 11 (263 mg, 0.07 mmol), C60 (252 mg,
0.35 mmol) and CBr4 (58 mg, 0.18 mmol) in dry toluene
(25 mL) was added DBU (26 mL, 0.18 mmol) under argon,
the mixture was stirred at room temperature for 24 h. The
reaction mixture was directly flash chromatographed,
eluting first with toluene to remove the excess C60, then
3:2 cyclohexane/acetone to afford 12 as a dark-red solid
(88 mg, 29%); [a]DZC10 (c 1.0, CHCl3); 1H NMR
(400 MHz, CDCl3): d 5.56 (t, 2H, JZ5.6 Hz, 2!NH),
5.18–5.14 (m, 8H, 8!H1), 5.13 (2d, 4H, J1,2Z3.5 Hz, 4!
H1), 5.07 (d, 2H, J1,2Z3.4 Hz, 2!H1), 4.50 (t, 4H, JZ
6.5 Hz, 2!CH2OOC); 13C NMR (100 MHz, CDCl3): d
172.93, 163.60 (4C, 2!COO–, 2!CONH–), 145.28,
145.16, 145.09, 145.08, 144.78, 144.59, 144.57, 144.50,
143.78, 142.98, 142.92, 142.89, 142.10, 141.81, 140.84,
138.90 (C60-sp2C), 98.91, 98.87, 98.85, 98.83, 98.81 (14C,
14!C1), 82.01, 81.92, 81.89, 81.75, 81.73, 81.65, 81.62,
81.58, 81.48, 80.85, 80.38, 80.35, 80.13, 80.08, 80.00,
79.90, 79.79, 70.98, 70.86, 70.79, 70.72 (56C, 14!C2, C3,
C4, C5), 71.48, 71.40, 71.32, 71.24, 71.22, 71.14, 67.39,
39.42, 36.82 (23C, 14!C6, 2!COOCH2, 2!OCH2, 2!
C60-sp3C, 2!CH2–NH, bridgehead C), 61.59, 61.45, 61.34,
61.31, 61.29, 58.91, 58.88, 58.59, 58.57, 58.55, 58.46,
58.36, 58.30 (40C, 40!OMe), 29.99, 29.63, 29.56, 29.50,
29.44, 29.33, 29.30, 29.26, 29.14, 28.50, 26.89, 26.81,
25.90, 25.76 (38C, 38!CH2); MS (FAB): m/z 4375.0 (60%,
1
133 (c 1.4, CHCl3); H NMR (400 MHz, CDCl3): d 5.19–
5.16 (m, 4H, 4!H1), 5.14 (2d, 2H, J1,2Z3.5 Hz, 2!H1),
5.08 (d, 1H, J1,2Z3.5 Hz, H1); 13C NMR (100 MHz,
CDCl3): d 98.77, 98.75, 98.69, 98.67 (7C, 7!C1), 81.85,
81.76, 81.72, 81.62, 81.59, 81.54, 81.32, 80.72, 80.22,
80.02, 79.90, 79.85, 79.69, 79.64, 70.93, 70.82, 70.74,
70.68, 70.6 (28C, 7!C2,C3,C4,C5), 71.38, 71.28, 71.19,
71.14, 71.02, 70.88 (8C, CH2OC7!C6), 61.49, 61.36,
61.35, 61.25, 61.21, 61.19, 58.84, 58.80, 58.54, 58.52,
58.50, 58.43, 58.31, 58.27 (20C, 20!OMe), 39.48
(CH2NH2), 29.89, 29.47, 29.43, 29.38, 29.30, 29.00,
28.18, 26.37, 25.83 (9C, 9!CH2); MS (FAB): m/z 1606.8
(20%, MCNaC), 1584.9 (35%, MCHC); Anal. Calcd for
C73H133O35N$3H2O: C, 53.49; H, 8.56; N, 0.85. Found: C,
53.41; H, 8.43; N, 1.06.
4.1.6. Malonic acid bis-(11-carboxy-undecyl) acid chlor-
ide (10). To a solution of Malonic acid bis-(11-carboxy-

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J. Yang et al. / Tetrahedron 60 (2004) 12163–12168
MCNaC); Anal. Calcd for C233H308O76N2$10H2O: C,
61.72; H, 7.31; N, 0.62. Found: C, 61.44; H, 7.07; N, 0.96.
¨
7. Lindstrom, U. M. Chem. Rev. 2002, 102, 2751–2771.
8. Cordes, E. H. Pure Appl. Chem. 1978, 50, 617–625.
9. Cordes, E. H.; Dunlop, R. B. Acc. Chem. Res. 1969, 2,
329–337.
4.1.9. 2:1 b-Cyclodextrin/fullerene[60] conjugate (15).
To a solution of 14 (20.5 mg, 0.021 mmol) in dry CH2Cl2
(2 mL) under argon in ice-bath was added triethylamine
(11.8 mL) and 9 (66.6 mg, 0.042 mmol, dissolved with 3 mL
of CH2Cl2). The mixture was stirred at room temperature for
18 h. After concentration at 30 8C, the residue was purified
by flash chromatography, eluting with 3:2 cyclohexane/
acetone to provide 15 (60 mg, 70%) as a dark-red solid. RfZ
0.5 (cyclohexane/acetone 1:1); [a]DZC5 (c 0.9, CHCl3);
1H NMR (400 MHz, CDCl3): d 6.91 (t, 2H, JZ5.7 Hz, 2!
NH), 5.18–5.14 (m, 8H, 8!H1), 5.13 (2d, 4H, J1,2Z3.5 Hz,
4!H1), 5.06 (d, 2H, J1,2Z3.4 Hz, 2!H1), 4.96 (s, 4H, 2!
OCCH2COO); 13C NMR (100 MHz, CDCl3): d 165.59,
162.44 (4C, 2!COO–, 2!CONH–), 145.27, 145.18,
144.92, 144.81, 144.69, 144.65, 144.40, 144.33, 143.79,
143.04, 142.93, 142.09, 141.70, 140.98, 139.01 (C60–sp2C),
98.89, 98.84, 98.82, 98.80, 98.76 (14C, 14!C1), 81.99,
81.90, 81.87, 81.73, 81.63, 81.59, 81.55, 81.44, 80.84,
80.36, 80.34, 80.14, 80.05, 79.96, 79.85, 79.78, 70.97,
70.87, 70.84, 70.77, 70.70 (56C, 14!C2, C3, C4, C5), 71.47,
71.38, 71.30, 71.23, 71.20, 71.12, 66.50, 39.63 (23C, 14!
C6, 2!COOCH2, 2!OCH2, 2!C60–sp3C, 2!CH2–NH,
bridgehead C), 61.60, 61.45, 61.44, 61.33, 61.29, 61.27,
58.91, 58.86, 58.57, 58.55, 58.46, 58.34, 58.29 (40C, 40!
OMe), 29.97, 29.56, 29.52, 29.50, 29.46, 29.44, 29.29,
26.92, 26.80, 25.89 (18C, 18!CH2); MS (FAB): m/z 4094.5
(20%, MCNaC); Anal. Calcd for C213H268O76N2$8H2O: C,
60.67; H, 6.79; N, 0.66. Found: C, 60.36; H, 6.95; N, 0.87.
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