Synthesis of four mono-functionalized α-cyclodextrin derivatives for further confirming DIBAL-H-promoted bis-de-O-methylation mechanism

Article abstract of DOI:10.1016/j.tet.2013.03.070

In our previous studies, a mechanism for DIBAL-H promoted regioselective bis-de-O-methylation of per-O-methylated cyclodextrin (CD) was proposed based on per-O-methylated β-CDs. As a further step to this work, four per-O-methylated α-CD derivatives (6, 7, 11, and 18) with mono functional group at the secondary rim have been designed and synthesized. Using DIBAL-H as a chemical 'scalpel', we found that (1) only the O-methyl at C-2^A of 6 could be easily removed and (2) the O-methyl at C₃B could be firstly regioselectively removed slowly, followed by a rapid removal of the second O-methyl at C₂A to provide 3. Combined with our previous studies, we think that not only O-3^B-methyl but also O-2^A and O-3^B are necessary for the formation of 'tweezers' during DIBAL-H promoted bis-de-O-methylation reaction of per-O-methylated CD.

Full text of DOI:10.1016/j.tet.2013.03.070

Tetrahedron 69 (2013) 4053e4060
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of four mono-functionalized -cyclodextrin derivatives for
a
further confirming DIBAL-H-promoted bis-de-O-methylation
mechanism
,
,
b
Sulong Xiao a b, Ming Yang a, Fei Yu a, Lihe Zhang a, Demin Zhou a , Pierre Sinay ,
*
€
Yongmin Zhang b
,c,
*
a State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
b
ꢀ
ꢀ
Institut Parisien de Chimie Moleculaire, CNRS UMR 7201, Universite Pierre et Marie Curie-Paris 6, 4 place Jussieu, 75005 Paris, France
c Institute for Interdisciplinary Research, Jianghan University, Wuhan Economic and Technological Development Zone, Wuhan 430056, China
a r t i c l e i n f o
a b s t r a c t
Article history:
In our previous studies, a mechanism for DIBAL-H promoted regioselective bis-de-O-methylation of per-
Received 8 February 2013
Received in revised form 8 March 2013
Accepted 18 March 2013
Available online 21 March 2013
O-methylated cyclodextrin (CD) was proposed based on per-O-methylated
b-CDs. As a further step to this
work, four per-O-methylated -CD derivatives (6, 7, 11, and 18) with mono functional group at the
a
secondary rim have been designed and synthesized. Using DIBAL-H as a chemical ‘scalpel’, we found that
B
(1) only the O-methyl at C-2A of 6 could be easily removed and (2) the O-methyl at C3 could be firstly
A
regioselectively removed slowly, followed by a rapid removal of the second O-methyl at C2 to provide 3.
Keywords:
Combined with our previous studies, we think that not only O-3B-methyl but also O-2A and O-3B are
necessary for the formation of ‘tweezers’ during DIBAL-H promoted bis-de-O-methylation reaction of
per-O-methylated CD.
a
-Cyclodextrin
DIBAL-H
Mechanism
Synthesis
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
well known that highly selective modification of only one hydroxyl
group of native CDs to obtain mono-functionalized per-O-methyl-
a
-,
b
- and
g-cyclodextrins (CDs) are macrocyclic oligomers of
D-
ated CDs remains a significant challenge for synthetic chemists.10
glucose with the secondary C2 and C3 hydroxyl groups on the
secondary rim and the primary C6 hydroxyl group on the primary
In our ongoing program to selective de-O-alkylation of a- and b-
per-O-alkylated CDs by diisobutylaluminium hydride (DIBAL-H),11
rim.1 Due to their different hydrophobic cavity volume (for
a
-CD:
a general simple way to access 2A,3B-dihydroxyl-per-O-methyl-
0.174,
b-CD: 0.262, and
g
-CD: 0.427 nm3),2 CDs have the ability to
ated a- and b-CD from per-O-methylated a- and b-CD was de-
form hosteguest or inclusion complexes with a large range of hy-
drophobic molecules, which made them potentially useful in the
fields of pharmacology,3 analytical chemistry,4 enzyme mimics,5
etc. However, the relatively low solubility of native CDs in water
veloped in our laboratory (Scheme 1).12 As an extension to this
study, unprecedented regioselective synthesis of two tetra-de-O-
methylated a b
-CDs13 and tetra- or hexa-de-O-methylated -CDs14
were discovered when a large excess of DIBAL-H was used as
a chemical ‘scalpel’ (Scheme 2).
(e.g., 14.5 g and 1.85 g in 100 mL for a-CD and b
-CD, respectively)6
and organic solvents (e.g., methanol, ethanol, acetonitrile, and
tetrahydrofuran)7 significantly limits their utility. Per-O-methyl-
ated CDs and their derivatives have attracted considerable atten-
tion due to their improved solubility both in water and in organic
solvents.8 Much effort has been directed toward the synthesis of
novel per-O-methylated CDs with various functional groups.9 It is
These reactions are remarkable in two ways: firstly, de-O-
methylation takes place selectively on the secondary rim of
a
- or
b
a
-CD, which is strikingly different from the one of per-O-benzylated
- or
b-CD, where only the primary rim is selected for de-O-
benzylation (Scheme 3);11a secondly, only the pair of hydroxyl
groups is obtained, which occurs on two adjacent sugars to give
diol, tetrol or hexol, respectively.
Recently, a mechanism for DIBAL-H promoted regioselective bis-
de-O-methylation of per-O-methylated cyclodextrin (CD) was pro-
posed based on per-O-methylated
step to this work, we extend our studies on per-O-methylated
to further confirm the mechanism. We report herein the preparation
b
-CDs by our group.15 As a further
* Corresponding authors. Tel.: þ33 1 44276153; fax: þ33 1 44275504 (Y.Z.); tel./
fax: þ86 10 82805519 (D.Z.); e-mail addresses: deminzhou@bjmu.edu.cn (D. Zhou),
yongmin.zhang@upmc.fr (Y. Zhang).
a
-CD
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.070

4054
S. Xiao et al. / Tetrahedron 69 (2013) 4053e4060
OMe
OMe
MeO
O
MeO
O
O
O
O
O
O
O
O
O
Me
O
Me
O
Me
Me
O
Me
O
O OH
O
Me
O
O
OMe
Me
OMe
O
O
OH
(OMe)16 or 19
O
O
DIBAL-H (6.0~7.0 eq)
Toluene, 50oC, 3h
Me
Me
Me
Me
Me
Me
α/β
2A
O
O
Me
MeO
MeO
3B
O
O
O
O
O
O
O
O
O
O
Me
Me
Me
Me
Me
O
Me
O
O
O
OH
OH
Me
Me
n
n
O
O
O
O
O
O
55 %
OMe
O
OMe n=1, 2
O
MeO
MeO
n=1, 2
Scheme 1. Bis-de-O-methylation of per-O-methylated a- and b-CDs by DIBAL-H.
OMe
OMe
OMe
MeO
O
MeO
O
O
MeO
O
O
O
O
O
O
O
O
O
O
O
O
O
Me
Me
O
O
H
Me
O
Me
Me
Me
OH
O
O
O
O
O
Me
O
H
O
O
Me
Me
Me
Me
OMe
HO
OMe
OMe
O
H
O
OH
O
O
O
O
Me
Me
DIBAL-H (40 eq)
Me
+
O
O
Toluene, R.T., 6 h
Me
O
Me
Me
MeO
MeO
O
H
MeO
O
O
O
O
O
O
O
O
O
O
Me
Me
O
O
Me
Me
Me
Me
O
Me
O
O
HO
O
Me
O
O
O
O
Me
Me
Me
O
O
O
O
O
O
O
O
O
OMe
OMe
O
OMe
O
MeO
MeO
MeO
19 %
45 %
OMe
OMe
OMe
MeO
MeO
O
MeO
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
Me
Me
Me
O
O
H
Me
H
Me
Me
Me
Me
OMe
OMe
OMe
O
O
OMe
O
Me
O
H
O
H
O
O
O
H
O
O
O
O
Me
Me
O
OH
O
O
Me
O
O
O
O
DIBAL-H (50.0 eq)
Toluene, RT, 28h
Me
O
Me
O
O
O
H
Me
O
Me
O
MeO
MeO
MeO
Me
Me
Me
Me
Me
Me
O
Toluene, RT, 3h
O
O
O
O
O
HO
O
O
O
Me
O
Me
O
Me
Me
Me
Me
O
O
Me
O
Me
Me
Me
OMe
O
HO
O
OMe
45%
O
O
O
O
O
O
O
O
OH
O
O
O
O
O
O
O
O
O
MeO
MeO
MeO
O
O
O
MeO
MeO
OMe
Scheme 2. The di-bis-de-O-methylation or tri-bis-de-O-methylation of per-O-methylated
a- and
b-CDs by a large excess of DIBAL-H.
OBn
OBn
BnO
O
BnO
O
O
O
O
O
O
O
O
O
OH
OH
Bn
O
Bn
Bn
O
O
Bn
O
O
Bn
D
O
O
Bn
A
O
Bn
OBn
O
O
Bn
O
O
OH
O
Bn
Bn
O
(OBn)16 or 19
Bn
Bn
Bn
Bn
DIBAL-H (120-140 eq)
Toluene, 30-50oC, 2h
α/β
O
Bn
BnO
O
Bn
O
O
O
HO
O
O
O
O
O
Bn
O
O
Bn
Bn
Bn
O
Bn
O
Bn
O
Bn
O
Bn
n
n
O
O
O
O
O
O
OBn
O
OBn
O
BnO
BnO
n=1, 2
n=1, 2
b-CD by DIBAL-H.
82 %
Scheme 3. Bis-de-O-benzylation of per-O-benzylated
of four mono-functionalized per-O-methylated
a
-CDs (6, 7, 11, and
per-O-methylated a-CD derivatives. The structure of 3 was con-
18) from per-O-methylated
of DIBAL-H.
a
-CD 1, and their behaviors upon actions
firmed by 1D NMR, 2D NMR, and HRMS and was further confirmed
by its acetylated derivative 5. 1H NMR spectrum of 5 showed two
acetyl groups at
d
2.20, 2.22 ppm, while 13C NMR spectrum dis-
2. Results and discussion
played two methyl and carbonyl groups of the acetate at 21.45,
21.68, and 170.39 (2C, 2ꢀ C]O) ppm, respectively. The low-field
doublets of doublet at 4.70 ppm (J1,2¼2.6 and J2,3¼10.3 Hz) and
5.47 (J2,3¼10.1 and J2,3¼9.0 Hz), each referring to 1H, were assigned
Synthesis of the four mono-functionalized per-O-methylated a-
CDs (6, 7, 11, and 18) is summarized in Scheme 4. 2A,3B-diol 3, ob-
tained after careful silica gel column chromatography (CH2Cl2/
CH3OH: 50/1e25/1) according to our previously reported
method,12,15 which is the key intermediate to synthesize novel
A
to H2 and H3B, respectively, and two carbons appearing at 71.66
and 74.38 ppm, should be assigned to C3B and C2A, respectively, due
to the acetylation of the hydroxyl groups.

S. Xiao et al. / Tetrahedron 69 (2013) 4053e4060
4055
OAc
(B)
OMe
MeO
O
O
O
O
O
(OMe)17
(OMe)16
(OMe)16
Me
Me
Me
Me
O
Me
O
O
O
O
Me
α
α
α
α
OMe
O
O
Me
Me
(A)
4, 93%
O
MeO
H
OCH3
OCH3
OAc
O
O
O
O
Me
(b)
8, 87%
11, 89%
Me
OH
Me
O
O
O
Me
O
O
O
(b)
(g)
OMe
O
(OMe)17
MeO
(OMe)16
(OMe)16
+
(OMe)16
(OMe)16
(OMe)16
(OMe)16
(a)
(f)
α
2, 7.8%
α
α
α
2A
3B
(OMe)16
(c)
OCH3 OH
OCH3
O
O
O
O
OCH3
OCH3 OCH3
Ph
Ph
α
6, 78%
1
O
S
9, 37%
10, 31%
OH
OH
(b)
(OMe)16
(OMe)16
(OMe)16
+
3, 50%
α
α
(f)
α
α
(d)
OH
OCH3
7, 15% from 3;
97% from 14
OAc OAc
O
O
OCH3
O
O
OCH3
16, 83%
Ph
5, 86%
Ph
(e)
(OMe)16
17, 10%
O
S
(OMe)16
(c)
(b)
(g)
(b)
α
α
α
(OMe)16
(OMe)16
OBn OH
OAc
13, 92%
OBn
OBn
14, 80%
OCH3
α
α
12, 87%
OAc
OCH3
15, 95%
OCH3
18, 74%
H
Scheme 4. Synthesis of the mono-functionalized per-O-methylated
a
-CD derivatives. Reagents and condition: (a) DIBAL-H (9.0 equiv), toluene, 0.2 M, 18 h, 0 ꢁC; (b) Ac2O, pyridine,
DMAP, rt, 18 h; (c) CH3I, NaH, DMF; (d) BnBr, NaH, DMF; (e) Pd/C, H2, CH3OH; (f) O-phenyl chlorothioformate, DMAP, pyridine, CH2Cl2; (g) AIBN, tributylstannane, toluene, 80 ꢁC.
A
B
As the hydroxyl group at C2 is more acidic10b than that at C3
,
was very difficult because their polarities are very similar (Rf¼0.24,
petroleum ether/acetone¼1:1). According to HPLC analysis, the
ratio of 9:10 is 55:45 (CH3OH/H2O: 60/40 by volume). As far as we
are aware the only example of this result in the literature was re-
ported by Remy et al.,16 as they observed in a similar reaction the
formation of a side product with replacement of C]S group by C]O
group in 8.3% yield. The mixture was subjected to deoxygenation
reaction before separation was achieved. According to the classical
BartoneMcCombie conditions (Bu3SnH, AIBN, 100 ꢁC),17 desired
compound 11 was obtained in 49% yield and compound 10 was
recovered in 40% yield. 1H NMR spectrum of compound 11 showed
consequently the reaction with an electrophilic reagent was ex-
pected to happen at C2 predominantly. In our experiments, se-
lective O-methylation of 3 at C2 with methyl iodide and sodium
hydride in DMF at room temperature afforded 6 in 80% yield, and its
regioisomer 7 was a minor component (15%). Like compound 3, the
structures of 6 and 7 were also confirmed by their acetylation de-
rivatives. 1H NMR spectrum of 8 displayed a deshielded methine
A
A
signal at
d
5.45 (dd, J2,3¼9.3 and J3,4¼9.2 Hz), should be assigned to
H3B, and 13C NMR spectrum displayed one carbon at 71.67 ppm,
should be assigned to C3B, due to the acetylation of C3B, indicating
that methylation of 3 took place at position C2A predominantly. On
two sets of peaks at d 1.96e2.05 and 2.31e2.39 ppm, corresponding
the other hand, the 1H NMR spectrum of acetylated compound 15
to two protons at C3B, while 13C NMR spectrum displayed a signal at
A
B
showed a deshielded signal for H2 at
d
4.65 (dd, J1,2¼3.1 and
29.24 ppm, corresponding to C3
.
J2,3¼10.3 Hz) and 13C NMR spectrum displayed one carbon at
The same reaction was also carried out for compound 7. As for
compound 6, two compounds (16 and 17) were formed from
compound 7 under an inert atmosphere. Interestingly, unlike the
mixture of compound 9 and 10, these two compounds could be
separated out by chromatography and thus characterized, re-
spectively, by 1H NMR, 13C NMR, 1He1H COSY, 1He13C COSY, and
HRMS. Compound 16 were obtained as the main product in 83%
yield. Deoxygenation of compound 16 proceeded smoothly in the
presence of Bu3SnH and AIBN to give compound 18 in 74% yield. 1H
74.25 ppm, should be assigned to C2A, indicating that methylation
B
took place at position C3
.
As the yield for 7 is too low (only in 15%) by this method,
a method for selective O-methylation of the C3 hydroxyl group
was achieved from 3 in a convenient three-step procedure in an
excellent overall yield (in 64% yield over three steps). Firstly, a se-
B
A
lective protection of the hydroxyl group at C2 by benzyl group to
give 12, whose structure was confirmed again from 1H and 13C NMR
spectrum of acetylated derivative 13. The remaining hydroxyl
NMR spectrum of 18 showed two sets of peaks at
d 1.65e1.71 and
B
group at C3 of 12 was then methylated to give 14, which was fi-
2.27e2.32 ppm, corresponding to two protons at C2A, while 13C
nally hydrogenolyzed with 10% Pd/C to give 7.
NMR spectrum displayed a signal at 35.49 ppm, corresponding to
A
Surprisingly, when transformation of 6 into 9 was performed
with O-phenyl chlorothioformate at 100 ꢁC under nitrogen, an un-
expected compound 10 was formed with 9 as judged by the results
of 1H NMR and 13C NMR spectra of the mixture. Trying to separate
the two components at this stage by usual column chromatography
C2
.
Since the preparation of mono-functionalized per-O-methyl-
ated-a-CDs (6, 7, 11, and 18) had been accomplished, we turned our
attention to investigation of their behaviors upon action of DIBAL-H
(Scheme 5). The reaction conditions were the same as that used for

4056
S. Xiao et al. / Tetrahedron 69 (2013) 4053e4060
(OMe)16
α
DIBAL-H
DIBAL-H
(OMe)16
(OMe)16
OCH3 OCH3
α
α
1
X
(OMe)16
OH
OCH3
OH
OH
α
3
7
DIBAL-H
OCH3 OH
6
(OMe)16
DIBAL-H
(OMe)16
(OMe)16
(OMe)16
DIBAL-H
α
α
α
α
X
X
H
OCH3
OCH3
H
OH
H
H
OH
11
18
Scheme 5. DIBAL-H promoted de-O-methylation reactions of compounds 6, 7, 11, and 18. Reagents and condition: DIBAL-H (9.0 equiv), toluene, 0.2 M, 18 h, 0 ꢁC.
A
B
preparing the compound 3. As expected, when 2A-hydroxyl-per-O-
with DIBAL-H slowly between two methoxy groups at C2 and C3
methylated-
a
-CD 7 was treated with a commercially available
located on two adjacent sugar units, followed by de-O-methylation
at C3B to provide the intermediate 21; the second step would be the
formation of the complex of 22 with an excess of DIBAL-H quickly
DIBAL-H (0.2 M, 9 equiv) for 18 h at 0 ꢁC in toluene, no new product
was formed on TLC analysis, and the recovered product was char-
acterized by NMR as the starting material. Interestingly, when 3B-
A
B
between the methoxy group at C2 and the hydroxyl group at C3
,
hydroxyl-per-O-methylated-
a
-CD 6 was treated under the same
with participation of the interglycosidic oxygen atom, demethyla-
A
condition, the starting material disappeared rapidly (within 0.5 h),
and a new spot with the same Rf as 3 on TLC appeared solely which,
after purification, showed the identical 1H NMR and 13C NMR
spectra as 3 obtained from 1 under the same condition. This
tion at C2 then proceeds via complex 23 to afford almost quanti-
tatively the 2A,3B-diols. In both cases, the presence of a C2 methoxy
group and a C3 methoxy or hydroxyl group are necessary for
complex formation.
OMe
O
OMe
O
OMe
O
OMe
O
MeO
MeO
O
O
Me
Me
O
O
OMe
O
OMe
O
O
O
Al
Al
Per-O-methylated α and β-CDs
O
O
O
Me
O
Me
Me
O
Al
Me
O
Me
O
Me
O
O
O
n
n
20
19
n = 4 or 5
n = 4 or 5
-CH4
OMe
O
OMe
O
OMe
O
OMe
O
OMe
O
OMe
MeO
MeO
MeO
O
O
O
O
Al
O
O
Me
Me
Al
O
OMe
O
OMe
OMe
O
Me
O
O
O
CH4
Al
O
O
O
Al
O
O
O
O
Me
Me
Me
O
Al
O
O
2A,3B-diols
Me
Me
Me
O
O
n
O
O
H2O
O
O
n
n
21
23
22
n = 4 or 5
n = 4 or 5
n = 4 or 5
Scheme 6. Proposed mechanism for the formation of 2A,3B-diols from per-O-methylated
a
and b-cyclodextrins.
particular behavior met during this reaction is not so surprising,
since several authors already reported ‘reactivity discrim-
inations’.6,8b,12,18 This work complements de-O-methylation per-
formed with phenylthiotrimethylsilane reported by Chaise et al.,9a
3. Conclusion
Starting from per-O-methylated
per-O-methylated -CD derivatives were prepared in a regiose-
a-CD, four mono-functionalized
a
which allow access to only 3B-hydroxyl-per-O-methyl-
a
-CD 6 by
lective manner. All the products were unambiguous characterized
by 1H and 13C NMR, 1He1H COSY, 1He13C HMQC or HSQC, and
HRMS. This study further confirmed that the O-methyl at C3B could
be firstly regioselectively removed slowly, followed by a rapid re-
removing the methyl group at C3B. However, no reaction was ob-
served of the other two deoxy-derivatives at C2 and C3 (11 and 18)
under these reaction conditions.
A
Combined with our previous studies,15 we think that the DIBAL-
H promoted regioselective bis-de-O-methylation of per-O-methyl-
ated CDs may include two steps (Scheme 6): the first step would
consist in the formation of the complex of per-O-methylated CDs
moval of the second O-methyl at C2 to provide 2A,3B-diol. More-
over, not only O-3B-methyl but also O-2A and O-3B methyls are
necessary for the formation of ‘tweezers’ during DIBAL-H promoted
bis-de-O-methylation reaction of per-O-methylated CD.

S. Xiao et al. / Tetrahedron 69 (2013) 4053e4060
4057
4. Experimental
4.1. General
subjected to flash chromatography (eluent: CH2Cl2/CH3OH¼30:1)
to give 35.1 mg (93%) of compound 4 as a white foam. Rf¼0.39
(CH2Cl2/CH3OH¼10:1);
[
a]
þ128.8 (c 1.0, CHCl3). 1H NMR
D
(400 MHz, CDCl3):
d
2.08 (s, 3H, CH3CO), 3.16e3.20 (m, 6H, 6ꢀ H2),
Optical rotations were measured at 20ꢂ2 ꢁC with a Perkin Elmer
Model 343 digital polarimeter, using a 10 cm, 1 mL cell. High Reso-
lution Mass Spectrometry (HRMS) were obtained with a LTQdOrbi-
trap spectrometer (ThermoFischer Company) or APEX IV FT-MS
(7.0 T) spectrometer (Bruker). NMR spectra were recorded on
a Bruker DRX 400 spectrometer or Varian INONVA-500 spectrome-
terat ambient temperature.1H NMR chemicalshifts are referencedto
residual protic solvent (CDCl3, dH¼7.28). 13C NMR chemical shifts are
referenced to the solvent signal (dC¼77.00 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 detected by charring with a 10%
solution of sulfuric acid in ethanol. Flash column chromatography
was performed on silica gel 60 (230e400 mesh, E. Merck or
200e300 mesh, Qingdao Haiyang Chemical Co. Ltd.). HPLC was
carried on a Varian Star instrument using a 330 UVevis, PDA detector
and the chromatographic data was acquired by LC workstation ver-
sion 6.20.
3.39 (s, 3H, OCH3 (C6)), 3.41 (br s, 12H, 4ꢀ OCH3 (C6)), 3.50 (2ꢀ s,
12H, 4ꢀ OCH3 (C2)), 3.51 (s, 6H, 2ꢀ OCH3 (C2)), 3.52 (s, 3H, OCH3
(C2)), 3.54 (m, 1H, H4A), 3.64 (s, 6H, 2ꢀ OCH3 (C3)), 3.65 (2ꢀ s, 9H,
3ꢀ OCH3 (C3)), 3.66 (s, 3H, OCH3 (C3)), 3.92 (m, 1H, H5A), 3.44e3.92
(m, 26H, 6ꢀ H3, 5ꢀ H4, 5ꢀ H5, 5ꢀ H6a, 5ꢀ H6b), 4.26 (dd, 1H,
J5,6a¼4.6 Hz, J6a,6b¼12.0 Hz, H6aA), 4.59 (m, 1H, H6bA), 5.04e5.07 (m,
6H, 6ꢀ H1); 13C NMR (100 MHz, CDCl3):
d 20.81 (CH3CO), 57.79,
57.84, 58.16 (6C, 6ꢀ OCH3 (C2)), 58.96, 59.09 (5C, 5ꢀ OCH3 (C6)),
61.77, 61.80, 61.87 (6C, 6ꢀ OCH3 (C3)), 63.72 (C6A), 69.69 (C5A),
70.74, 71.28, 71.46 (5C, 5ꢀ C6), 71.22, 71.42 (5C, 5ꢀ C5), 81.18, 81.21,
81.32, 82.00, 82.06, 82.15, 82.22, 82.30, 82.40, 82.45, 82.59 (18C, 6ꢀ
C2, 6ꢀ C3, 6ꢀ C4), 99.65, 99.89, 100.09, 100.18, 100.55 (6C, 6ꢀ C1),
170.49 (C]O); HRMS calcd for C55H96NaO31 [MþNa]þ: 1275.5828.
Found 1275.5829.
4.4. 2A,3B-O-Diacetyl-per-O-methyl-
a-cyclodextrin (5)
To a solution of 3 (31.8 mg, 0.027 mmol) in dry pyridine (2 mL)
was added 3.2 mg of DMAP (0.027 mmol,1.0 equiv) and 1 mL Ac2O at
room temperature. The reaction mixture was stirred for 18 h under
nitrogen. The solvent was removed in vacuo. The residue was sub-
jected to flash chromatography (eluent: CH2Cl2/CH3OH¼30:1) to
give 29.3 mg (86%) of compound 5 as a white foam. Rf¼0.40 (CH2Cl2/
4.2. 6A-Hydroxyl-per-O-methyl-
2A,3B-dihydroxyl-per-O-methyl-
a
-cyclodextrin (2) and
a-cyclodextrin (3)
To a solution of dried per-O-methyl-a-cyclodextrin (670.5 mg,
0.55 mmol) in anhydrous toluene (21.4 mL) was added 3.29 mL
(4.93 mmol, 9.0 equiv), DIBAL-H (1.5 M in toluene) at 0 ꢁC under
nitrogen. The reaction mixture was stirred at 0 ꢁC for 18 h under
nitrogen. Aqueous HCl (1 M) was carefullyadded dropwise to quench
the reaction and the mixture was stirred vigorously at room tem-
perature for 30 min. The toluene phase was separated and the water
phase was extracted by ethyl acetate (3ꢀ20 mL). The combined or-
ganic phase was washed with brine, dried with MgSO4, filtrated, and
the solvent was removed in vacuo. The residue was subjected to flash
chromatography (eluent: CH2Cl2/CH3OH¼50:1e25:1) to give com-
pound 2 and 3 in 7.8% and 50% yield, respectively.12
CH3OH¼10:1); [
a
]D þ140.0 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
d
2.20 (s, 3H, CH3CO), 2.22 (s, 3H, CH3CO), 3.12e3.21 (m, 4H, 4ꢀ H2),
3.22 (dd, 1H, J1,2¼3.1 Hz, J2,3¼10.1 Hz, H2B), 3.40 (s, 3H, OCH3 (C6)),
3.41 (2ꢀ s,15H, 5ꢀ OCH3 (C6)), 3.44 (s, 3H, OCH3 (C2)), 3.48 (s, 6H, 2ꢀ
OCH3 (C2)), 3.51 (s, 6H, 2ꢀ OCH3 (C2)), 3.57 (s, 3H, OCH3 (C3)), 3.58
(m, 1H, H5), 3.59 (s, 3H, OCH3 (C3)), 3.62 (s, 3H, OCH3 (C3)), 3.65 (s,
3H, OCH3 (C3)), 3.67 (m,1H, H3A), 3.70 (s, 3H, OCH3 (C3)), 3.72 (m,1H,
H4B), 3.53e3.96 (m, 25H, 4ꢀ H3, 5ꢀ H4, 5ꢀ H5, 6ꢀ H6a, 5ꢀ H6b), 4.08
(dd, 1H, J5,6b¼2.2 Hz, J6a,6b¼10.8 Hz, H6b), 4.70 (dd, 1H, J1,2¼2.6 Hz,
J2,3¼10.3 Hz, H2A), 4.99 (d, 1H, J1,2¼2.6 Hz, H1A), 5.03e5.06 (m, 3H,
3ꢀ H1), 5.09 (d,1H, J1,2¼3.1 Hz, H1), 5.12 (d,1H, J1,2¼3.1 Hz, H1B), 5.47
The NMR data of 2 are in agreement with those reported
(t, J2,3¼10.1 Hz, J3,4¼9.0 Hz, H3B); 13C NMR (100 MHz, CDCl3):
d 21.45,
previously.19
21.68 (2C, 2ꢀ CH3CO), 57.52, 57.70, 57.78, 57.95, 58.24 (5C, 5ꢀ OCH3
(C2)), 58.78, 58.91, 58.95, 59.02, 59.04 (6C, 6ꢀ OCH3 (C6)), 61.46,
61.59, 61.71, 61.85, 62.06 (5C, 5ꢀ OCH3 (C3)), 70.69, 71.42, 71.45,
71.58, 71.87 (6C, 6ꢀ C6), 70.84, 71.12, 71.14, 71.50, 71.61 (6C, 6ꢀ C5),
71.66 (C3B), 74.38 (C2A), 79.87 (C2B), 78.40, 78.98, 80.80, 80.92,
80.93, 80.99, 82.18, 82.23, 82.31, 82.35, 82.56, 82.60, 82.62, 82.65,
82.83 (15C, 4ꢀ C2, 5ꢀ C3, 6ꢀ C4), 98.45 (C1A), 99.83, 99.88, 100.01,
100.22, 100.42 (5C, 5ꢀ C1), 170.39 (2C, 2ꢀ C]O); HRMS calcd for
C56H96NaO32 [MþNa]þ: 1303.5777. Found 1303.5763.
Compound 3: Rf¼0.20 (CH2Cl2/CH3OH¼15:1); [
a
]
þ144 (c 1.0,
D
CHCl3); 1H NMR (400 MHz, CDCl3):
d
3.16e3.21 (m, 6H, 6ꢀ H2), 3.39
(s, 9H, 3ꢀ OCH3 (C6)), 3.40 (3ꢀ s, 9H, 3ꢀ OCH3 (C6)), 3.41 (s, 3H,
OCH3 (C6)), 3.50 (2ꢀ s, 12H, 4ꢀ OCH3 (C2)), 3.52 (2ꢀ s, 6H, 2ꢀ OCH3
(C2)), 3.56 (s, 3H, OCH3 (C2)), 3.59 (m, 1H, H2A), 3.62 (2ꢀ s, 6H, 2ꢀ
OCH3 (C3)), 3.63 (s, 3H, OCH3 (C3)), 3.64 (s, 3H, OCH3 (C3)), 3.65 (s,
3H, OCH3 (C3)), 3.73 (s, 3H, OCH3 (C3)), 3.44e3.93 (m, 35H, 6ꢀ H3,
7ꢀ H4, 7ꢀ H5, 7ꢀ H6a, 7ꢀ H6b, OH), 3.99 (t, 1H, J2,3¼J3,4¼9.5 Hz,
H3B), 4.09 (br s, 1H, D2O exchangeable, OH), 5.01 (d, 1H, J1,2¼3.7 Hz,
H1A), 5.09e5.10 (m, 2H, 2ꢀ H1), 5.11e5.14 (m, 4H, 4ꢀ H1); 13C NMR
(100 MHz, CDCl3):
d
58.24, 58.29, 58.36, 58.44, 58.63, 58.85, 58.88,
4.5. 3B-Hydroxyl-per-O-methyl-
a-cyclodextrin (6)
58.91, 58.97 (13C, 6ꢀ OCH3 (C2), 7ꢀ OCH3 (C6)), 61.23, 61.30, 61.33,
61.35, 61.49, 62.11 (6C, 6ꢀ OCH3 (C3)), 70.35, 70.75, 70.85, 70.93,
71.64 (7C, 7ꢀ C5), 70.78, 71.16, 71.25, 71.33, 71.48 (7C, 7ꢀ C6), 71.72
(C3B), 73.40 (C2A), 80.02, 80.33, 80.95, 80.99, 81.29, 81.38, 81.58,
81.62, 81.75, 81.98, 82.01, 82.19, 82.37, 82.91 (19C, 6ꢀ C2, 6ꢀ C3, 7ꢀ
C4), 98.68, 98.93, 99.30, 99.46 (6C, 6ꢀ C1), 102.01 (C1A); HRMS calcd
for C52H96NO30 [MþNH4]þ: 1214.6012. Found 1214.5599;
C52H92NaO30 [MþNa]þ: 1219.5566. Found 1219.5550.
To a solution of 3 (97.4 mg, 0.081 mmol) in anhydrous THF
(5 mL) was added 3.3 mg (60%, 0.081 mmol, 1.0 equiv) of NaH at
0
ꢁC under nitrogen. After the reaction mixture was stirred at 0 ꢁ
C
for 1 h, 5.0 mL of CH3I (0.081 mmol, 1.0 equiv) was added. The re-
action mixture was stirred at 0 ꢁC for 6 h and then kept at room
temperature for another 12 h under nitrogen. CH3OH was added
dropwise to quench the reaction and the solvent was removed in
vacuo. The residue dissolved with CH2Cl2, washed with brine, dried
with MgSO4, filtrated, and the solvent was removed in vacuo. The
residue was subjected to flash chromatography (eluent: CH2Cl2/
EtOAc/CH3OH¼10:10:1) to give 15.0 mg (15%) of 7 firstly, then
76.4 mg (78%) of 6 as white foam. Rf¼0.38 (CH2Cl2/CH3OH/
4.3. 6A-O-Acetyl-per-O-methyl-
a-cyclodextrin (4)
To a solution of 2 (36.5 mg, 0.030 mmol) in dry pyridine (2 mL)
was added 3.7 mg of DMAP (0.030 mmol, 1.0 equiv) and 1 mL Ac2O
at room temperature. The reaction mixture was stirred for 18 h
under nitrogen. The solvent was removed in vacuo. The residue was
EtOAc¼5:1:5); [
a]
D þ126.5 (c 1.0, CHCl3); the NMR data of 6 are in
agreement with those reported previously.9a

4058
S. Xiao et al. / Tetrahedron 69 (2013) 4053e4060
4.6. 3B-O-Acetyl-per-O-methyl-
a-cyclodextrin (8)
H
6a, 5ꢀ H6b), 3.97 ( m, 1H, H6b), 5.02e5.06 (m, 5H, 5ꢀ H1), 5.14 (d,
1H, J1,2¼3.2 Hz, H1B), 5.33 (m, 1H, H3B), 7.20e7.22 (m, 1H, arom-H),
By the same procedure described in 4.2, compound 8 was ob-
tained by flash chromatography (eluent: cyclohexane/acetone¼2:1)
as a white foam in 87% yield. Rf¼0.32 (cyclohexane/acetone¼1:1);
7.35e7.36 (m, 4H, arom-H); 13C NMR (100 MHz, CDCl3):
d 57.56,
57.60, 57.70, 57.81, 58.05, 58.31 (6C, 6ꢀ OCH3 (C2)), 58.90, 58.93,
58.96, 59.05 (6C, 6ꢀ OCH3 (C6)), 61.67, 61.71, 61.84, 61.93, 61.98 (5C,
5ꢀ OCH3 (C3)), 70.70, 71.38, 71.69 (6C, 6ꢀ C6), 70.99, 71.10, 71.13,
71.21 (6C, 6ꢀ C5), 76.71 (C3B), 79.60 (C2B), 79.93 (C4B), 80.71, 80.87,
80.94, 82.15, 82.21, 82.25, 82.40, 82.50, 82.65, 82.73 (15C, 5ꢀ C2, 5ꢀ
C3, 5ꢀ C4), 99.90, 99.94, 100.05, 100.16, 100.31 (6C, 6ꢀ C1), 121.12,
125.61, 129.13, 153.37 (6C, 6ꢀ arom-C), 151.45 (C]O); HRMS calcd
for C60H98NaO32 [MþNa]þ: 1353.5933. Found 1353.5935.
[
a]
D þ129.7 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
d 2.14 (s, 3H,
CH3CO), 3.10e3.20 (m, 5H, 5ꢀ H2), 3.25 (dd, 1H, J1,2¼3.0 Hz,
J2,3¼10.5 Hz, H2B), 3.41 (s, 3H, OCH3 (C6)), 3.42 (2ꢀ s, 15H, 5ꢀ OCH3
(C6)), 3.44 (s, 3H, OCH3 (C2)), 3.47 (s, 3H, OCH3 (C2)), 3.48 (s, 3H, OCH3
(C2)), 3.49 (s, 3H, OCH3 (C2)), 3.50 (s, 3H, OCH3 (C2)), 3.51 (s, 3H, OCH3
(C2)), 3.58 (s, 3H, OCH3 (C3)), 3.60 (m, 1H, H5), 3.62 (s, 6H, 2ꢀ OCH3
(C3)), 3.63 (s, 3H, OCH3 (C3)), 3.70 (s, 3H, OCH3 (C3)), 3.80 (m, 1H,
H4B), 3.47e3.94 (m, 26H, 5ꢀ H3, 5ꢀ H4, 5ꢀ H5, 6ꢀ H6a, 5ꢀ H6b), 4.02
(dd,1H, J5,6b¼2.8 Hz, J6a,6b¼10.5 Hz, H6b), 4.96 (d,1H, J1,2¼2.8 Hz, H1),
5.01 (d, 1H, J1,2¼3.3 Hz, H1), 5.04e5.05 (m, 2H, 2ꢀ H1), 5.09 (d, 1H,
J1,2¼3.3 Hz, H1), 5.11 (d, 1H, J1,2¼3.0 Hz, H1B), 5.45 (dd, 1H,
Compound 11: Rf¼0.37 (CH2Cl2/CH3OH¼20:1); [
a]
þ133.5 (c
D
1.0, CHCl3); 1H NMR (400 MHz, CDCl3): 1.96e2.05 (m, 1H, H3aB),
d
2.31e2.39 (m, 1H, H3bB), 3.12 (dd, 1H, J1,2¼2.8 Hz, J2,3¼9.6 Hz, H2),
3.16e3.19 (m, 4H, 4ꢀ H2), 3.28e3.32 (m, 1H, H2B), 3.41 (s, 12H, 4ꢀ
OCH3 (C6)), 3.43 (s, 3H, OCH3 (C6)), 3.44 (s, 3H, OCH3 (C6)), 3.48 (s,
6H, 2ꢀ OCH3 (C2)), 3.50 (br s, 12H, 4ꢀ OCH3 (C2)), 3.61 (s, 3H, OCH3
(C3)), 3.63 (s, 3H, OCH3 (C3)), 3.65 (s, 6H, 2ꢀ OCH3 (C3)), 3.66 (s, 3H,
OCH3 (C3)), 3.71 (m, 1H, H4B), 3.48e3.90 (m, 28H, 5ꢀ H3, 5ꢀ H4, 6ꢀ
H5, 6ꢀ H6a, 6ꢀ H6b), 4.94 (d, 1H, J1,2¼3.2 Hz, H1), 5.03 (d, 1H,
J1,2¼3.2 Hz, H1B), 5.06e5.07 (m, 4H, 4ꢀ H1); 13C NMR (100 MHz,
J2,3¼10.5 Hz, J3,4¼9.0 Hz, H3B); 13C NMR (100 MHz, CDCl3):
d 21.39
(CH3CO), 57.52, 57.71, 57.73, 57.79, 58.21, 58.72, 58.88, 58.95, 58.98,
59.08 (12C, 6ꢀ OCH3 (C2), 6ꢀ OCH3 (C6)), 61.56, 61.69, 61.77, 61.89,
62.09 (5C, 5ꢀ OCH3 (C3)), 70.75, 71.35, 71.39, 71.48, 71.71, 71.84 (6C,
6ꢀ C6), 70.99, 71.09, 71.13, 71.15, 71.23, 71.32 (6C, 6ꢀ C5), 71.67 (C3B),
79.54, 80.75, 80.87, 80.92, 80.93, 82.19, 82.27, 82.29, 82.52, 82.54,
82.60, 82.62, 82.67, 82.73, 82.84 (16C, 5ꢀ C2, 5ꢀ C3, 6ꢀ C4), 79.78
(C2B), 99.68, 99.88, 100.15, 100.22, 100.31, 100.33 (6C, 6ꢀ C1), 170.84
(C]O); HRMS calcd for C55H96NaO31 [MþNa]þ: 1275.5828. Found
1275.5816.
CDCl3):
d
29.24 (C3B), 56.57, 57.62, 57.70, 57.79, 58.76, 58.93, 58.95,
59.00, 59.02, 59.10 (12C, 6ꢀ OCH3 (C2), 6ꢀ OCH3 (C6)), 61.59, 61.80,
61.82, 61.89 (5C, 5ꢀ OCH3 (C3)), 71.11, 71.15, 71.19, 71.51 (6C, 6ꢀ C5),
71.36, 71.46, 71.79 (6C, 6ꢀ C6), 76.13 (C4B), 76.51 (C2B), 81.12, 81.14,
81.19, 81.26, 81.87, 81.91, 81.98, 82.10, 82.17, 82.21, 82.29, 82.45,
82.50 (15C, 5ꢀ C2, 5ꢀ C3, 5ꢀ C4), 99.14 (C1B), 99.72, 99.91, 100.03,
100.21 (5C, 5ꢀ C1); HRMS calcd for C53H94NaO29 [MþNa]þ:
1217.5773. Found 1217.5778.
4.7. 3B-O-Phenoxythiocarbonyl-per-O-methyl-
a-cyclodextrin (9)
To a solution of 6 (170.3 mg, 0.14 mmol) in pyridine (2 mL) was
added 4-dimethylaminopyridine (34.2 mg, 0.28 mmol) and O-
phenyl chlorothioformate (290
mL, 2.1 mmol). The reaction mixture
4.9. 2A-O-Benzyl-3B-hydroxyl-per-O-methyl-
a-cyclodextrin (12)
was degassed under vacuum and urged with nitrogen three times,
then stirred under nitrogen balloon at 50 ꢁC for 10 h and concen-
trated. The residue dissolved with CH2Cl2, washed with brine, dried
with MgSO4, filtrated, and the solvent was removed in vacuo. The
residue was subjected to flash chromatography (eluent: petroleum
ether/acetone¼3:2) to recover 6 (48.5 mg), and then to give the
mixture of compound 9 and 10 (109.2 mg, 68%) as a white foam.
Compound 9: 13C NMR (125 MHz, CDCl3): 122.24, 126.47, 129.41,
153.42 (6C, 6ꢀ arom-C); compound 10: 13C NMR (125 MHz, CDCl3):
121.17, 125.67, 129.19, 153.87 (6C, 6ꢀ arom-C), 151.49 (C]O).
HPLC indicate that compound 9:10¼55:45.
To a solution of 3 (437.8 mg, 0.37 mmol) in anhydrous THF
(20 mL) was added 14.6 mg (60%, 0.37 mmol,1.0 equiv) of NaH at 0 ꢁC
under nitrogen. After the reaction mixture was stirred at 0 ꢁC for 1 h,
43.8 mL BnBr (0.37 mmol,1.0 equiv) was added. The reaction mixture
was stirred at 0 ꢁC for 6 h and then kept at room temperature for 12 h
under nitrogen. CH3OH was added dropwise to quench the reaction
and the solvent was removed in vacuo. The residue was dissolved
with CH2Cl2, washed with brine, dried with MgSO4, filtrated, and the
solvent was removed in vacuo. The residue was subjected to flash
chromatography (eluent: CH2Cl2/EtOAc/CH3OH¼10:10:1) to give
407.6 mg (87%) of 12 as a white foam. Rf¼0.44 (CH2Cl2/EtOAc/
4.8. 3B-O-Phenoxycarbonyl-per-O-methyl-
and 3B-deoxy-per-O-methyl-
-cyclodextrin (11)
b-cyclodextrin (10)
CH3OH¼5:5:1); [
a
]
þ134.8 (c 1.0, CHCl3); 1H NMR (400 MHz,
D
b
CDCl3):
d
3.15e3.18 (m, 4H, 4ꢀ H2), 3.29 (dd, 1H, J1,2¼3.3 Hz,
J2,3¼10.3 Hz, H2B), 3.35 (s, 3H, OCH3 (C6)), 3.36 (s, 3H, OCH3 (C6)),
3.37 (m, 1H, H2A), 3.39 (2ꢀ s, 9H, 3ꢀ OCH3 (C6)), 3.41 (s, 3H, OCH3
(C6)), 3.47 (s, 3H, OCH3 (C2)), 3.48 (br s, 6H, 2ꢀ OCH3 (C2)), 3.50 (s, 3H,
OCH3 (C2)), 3.52 (m, 1H, H4B), 3.55 (s, 3H, OCH3 (C2)), 3.62 (s, 3H,
OCH3 (C3)), 3.63 (s, 3H, OCH3 (C3)), 3.64 (br s, 6H, 2ꢀ OCH3 (C3)), 3.68
(m, 1H, H3A), 3.69 (s, 3H, OCH3 (C3)), 3.44e3.86 (m, 27H, 4ꢀ H3, 5ꢀ
H4, 6ꢀ H5, 6ꢀ H6a, 6ꢀ H6b), 4.10 (t, 1H, J2,3¼9.8 Hz, J3,4¼9.0 Hz, H3B),
4.62 (d, 1H, J1,2¼3.3 Hz, H1A), 4.73 (d, 1H, Jgem¼12.5 Hz, PhCH2), 4.88
(d, 1H, Jgem¼12.5 Hz, PhCH2), 5.00 (d, 1H, J1,2¼3.3 Hz, H1), 5.03e5.05
(m, 3H, 3ꢀ H1), 5.10 (d, 1H, J1,2¼3.3 Hz, H1B), 5.20 (s, 1H, D2O ex-
changeable, OH), 7.28e7.35 (m, 3H, 3ꢀ arom-H), 7.39e7.41 (m, 2H,
The mixture of compound 9 and 10 (54.3 mg) was dissolved in
anhydrous toluene (2 mL) and AIBN (3.3 mg, 0.02 mmol) was
added. The solution was degassed under vacuum and urged with
nitrogen three times, then tributylstannane (150 mL, 0.52 mmol)
was added. The mixture was stirred at 100 ꢁC for 2 h. After evap-
oration of toluene, the residue was dissolved in dichloromethane
(10 mL) then washed with brine, dried with MgSO4, filtrated, and
the solvent was removed in vacuo. The residue was subjected to
flash chromatography (eluent: CH2Cl2/CH3OH¼60:1e40:1) to re-
cover 21.7 mg 10 (40%) firstly, and then to give 25.2 mg (49%) of 11
as a white foam.
2ꢀ arom-H); 13C NMR (100 MHz, CDCl3):
d 57.55, 57.64, 57.78, 57.94
Compound 10: Rf¼0.39 (CH2Cl2/CH3OH¼20:1); [
a
]
þ138.2 (c
(5C, 5ꢀ OCH3 (C2)), 58.89, 58.90, 58.97, 59.01 (6C, 6ꢀ OCH3 (C6)),
61.74, 61.78, 61.87, 61.91 (5C, 5ꢀ OCH3 (C3)), 69.91, 71.09, 71.21, 71.30,
71.49 (6C, 6ꢀ C6), 71.12, 71.15, 71.35, 71.57 (6C, 6ꢀ C6), 71.61 (C3B),
73.70 (PhCH2), 78.51 (C2A), 80.75 (C2B), 81.04, 81.10, 81.27, 82.03,
82.12, 82.15, 82.25, 82.42, 82.48, 82.52, 83.68 (14C, 4ꢀ C2, 4ꢀ C3, 6ꢀ
C4), 82.71 (C3A), 99.94, 99.99, 100.04, 100.21, 100.26 (5C, 5ꢀ C1),
101.72 (C1A), 128.20, 128.51, 128.75, 137.07 (6C, 6ꢀ arom-C); HRMS
calcd for C59H98NaO30 [MþNa]þ: 1309.6035. Found 1309.6018.
D
1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
d
3.14e3.18 (m, 5H, 5ꢀ H2),
3.36 (dd, 1H, J1,2¼3.2 Hz, J2,3¼10.0 Hz, H2B), 3.41 (s, 12H, 4ꢀ OCH3
(C6)), 3.42 (s, 3H, OCH3 (C6)), 3.43 (s, 3H, OCH3 (C6)), 3.46 (s, 6H, 2ꢀ
OCH3 (C2)), 3.47 (s, 3H, OCH3 (C2)), 3.48 (s, 3H, OCH3 (C2)), 3.51 (s,
3H, OCH3 (C2)), 3.52 (s, 3H, OCH3 (C2)), 3.55 (s, 3H, OCH3 (C3)), 3.58
(s, 3H, OCH3 (C3)), 3.59 (2ꢀ s, 6H, 2ꢀ OCH3 (C3)), 3.65 (s, 3H, OCH3
(C3)), 3.87 (m,1H, H4B), 3.46e3.88 (m, 27H, 5ꢀ H3, 5ꢀ H4, 6ꢀ H5, 6ꢀ

S. Xiao et al. / Tetrahedron 69 (2013) 4053e4060
4059
4.10. 2A-O-Benzyl-3B-O-acetyl-per-O-methyl-
a
-cyclodextrin (13)
foam. Rf¼0.27 (cyclohexane/acetone¼3:2);
CHCl3). 1H NMR (400 MHz, CDCl3):
[
a
]
þ147.0 (c 1.0,
D
d
3.16e3.22 (m, 4H, 4ꢀ H2), 3.27
By the same procedure described in Section 4.2, compound 13
was obtained by flash chromatography (eluent: cyclohexane/
acetone¼2:1) as a white foam in 92% yield. Rf¼0.38 (cyclohexane/
(dd,1H, J1,2¼3.0 Hz, J2,3¼9.8 Hz, H2), 3.41 (s, 3H, OCH3 (C6)), 3.42 (3ꢀ
s, 15H, 5ꢀ OCH3 (C6)), 3.49 (s, 6H, 2ꢀ OCH3 (C2)), 3.50 (2ꢀ s, 9H, 3ꢀ
OCH3 (C2)), 3.53 (m, 1H, H2A), 3.63 (s, 3H, OCH3 (C3)), 3.64 (s, 3H,
OCH3 (C3)), 3.65 (s, 3H, OCH3 (C3)), 3.66 (s, 3H, OCH3 (C3)), 3.73 (s,
6H, 2ꢀ OCH3 (C3)), 3.88 (m, 1H, H3), 3.47e3.91 (m, 29H, 5ꢀ H3, 6ꢀ
H4, 6ꢀ H5, 6ꢀ H6a, 6ꢀ H6b), 4.27 (d, 1H, J2,OH¼10.5 Hz, D2O ex-
changeable, OH), 4.90 (d,1H, J1,2¼3.0 Hz, H1A), 5.05e5.08 (m, 5H, 5ꢀ
acetone¼1:1); [
a
]D þ130.9 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
d
1.95 (s, 3H, CH3CO), 3.12e3.19 (m, 4H, 4ꢀ H2), 3.25 (dd, 1H,
J1,2¼2.8 Hz, J2,3¼9.9 Hz, H2A), 3.29 (dd, 1H, J1,2¼3.3 Hz, J2,3¼10.5 Hz,
H2B), 3.33 (s, 3H, OCH3 (C6)), 3.37 (s, 3H, OCH3 (C6)), 3.40 (s, 3H, OCH3
(C6)), 3.41 (2ꢀ s, 9H, 3ꢀ OCH3 (C6)), 3.45 (s, 3H, OCH3 (C2)), 3.47 (s,
3H, OCH3 (C2)), 3.50 (s, 6H, 2ꢀ OCH3 (C2)), 3.51 (s, 3H, OCH3 (C2)),
3.54 (m,1H, H3A), 3.57 (s, 3H, OCH3 (C3)), 3.61 (s, 3H, OCH3 (C3)), 3.64
(s, 3H, OCH3 (C3)), 3.68 (s, 3H, OCH3 (C3)), 3.70 (s, 3H, OCH3 (C3)), 3.76
(m, 1H, H4B), 3.48e3.97 (m, 27H, 4ꢀ H3, 5ꢀ H4, 6ꢀ H5, 6ꢀ H6a, 6ꢀ
H6b), 4.62 (d,1H, J1,2¼2.8 Hz, H1A), 4.63 (d,1H, Jgem¼12.5 Hz, PhCH2),
4.76 (d, 1H, Jgem¼12.5 Hz, PhCH2), 5.00 (d, 1H, J1,2¼3.3 Hz, H1),
5.04e5.05 (m, 2H, 2ꢀ H1), 5.08 (d, 1H, J1,2¼3.0 Hz, H1), 5.12 (d, 1H,
J1,2¼3.0 Hz, H1B), 5.45 (dd, 1H, J2,3¼10.1 Hz, J3,4¼9.0 Hz, H3B),
7.30e7.31 (m,1H, arom-H), 7.34e7.38 (m, 2H, 2ꢀ arom-H), 7.41e7.43
H1); 13C NMR (100 MHz, CDCl3):
d 57.48, 57.62, 57.67, 57.77, 57.82
(5C, 5ꢀ OCH3 (C2)), 58.97, 59.00, 59.02, 59.07, 59.08 (6C, 6ꢀ OCH3
(C6)), 60.13, 61.47, 61.77, 61.80, 62.10 (6C, 6ꢀ OCH3 (C3)), 70.66, 71.28,
71.45, 71.61, 71.63 (6C, 6ꢀ C6), 71.11, 71.17, 71.19, 71.23, 72.10 (6C, 6ꢀ
C5), 73.90 (C2A), 80.47 (C3), 79.36, 81.15, 8.17, 81.21, 81.28, 82.10,
82.13, 82.19, 82.23, 82.42, 82.61, 82.69, 83.81 (16C, 5ꢀ C2, 5ꢀ C3, 6ꢀ
C4), 99.94, 99.99, 100.18, 100.32 (5C, 5ꢀ C1), 102.72 (C1A); HRMS
calcd for C53H94NaO30 [MþNa]þ: 1233.5722. Found 1233.5725.
4.13. 2A-O-Acetyl-per-O-methyl-
a-cyclodextrin (15)
(m, 2H, 2ꢀ arom-H); 13C NMR (100 MHz, CDCl3):
d 21.25 (CH3CO),
57.47, 57.68, 57.78, 57.98, 58.20 (5C, 5ꢀ OCH3 (C2)), 58.74, 58.91,
58.93, 58.95, 59.01 (6C, 6ꢀ OCH3 (C6)), 61.50, 61.65, 61.77, 61.86,
62.07 (5C, 6ꢀ OCH3 (C3)), 70.61, 71.29, 71.46, 71.64, 71.82 (6C, 6ꢀ C6),
70.92, 71.10, 71.17 (6C, 6ꢀ C5), 71.34 (C3B), 73.51 (PhCH2), 79.27 (C4B),
79.79 (C2B), 77.21, 80.86, 80.89, 80.91, 81.00, 82.16, 82.23, 82.29,
82.44, 82.53, 82.57, 82.62, 82.66, 82.84 (15C, 5ꢀ C2, 5ꢀ C3, 5ꢀ C4),
99.82, 100.08, 100.17, 100.29, 100.45 (6C, 6ꢀ C1), 127.88, 128.06,
128.41, 138.57 (6C, 6ꢀ arom-C), 170.95 (C]O); HRMS calcd for
C61H100NaO31 [MþNa]þ: 1351.6141. Found 1351.6130.
By the same procedure described in Section 4.2, compound 15
was obtained by flash chromatography (eluent: cyclohexane/
acetone¼2:1) as a white foam in 95% yield. Rf¼0.31 (cyclohexane/
acetone¼3:2); [
a
]D þ140.3 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
d
2.18 (s, 3H, CH3CO), 3.15e3.21 (m, 5H, 5ꢀ H2), 3.40 (s, 3H, OCH3
(C6)), 3.41 (s, 3H, OCH3 (C6)), 3.42 (2ꢀ s, 12H, 4ꢀ OCH3 (C6)), 3.50
(4ꢀ s, 12H, 4ꢀ OCH3 (C2)), 3.51 (s, 3H, OCH3 (C2)), 3.62 (s, 3H, OCH3
(C3)), 3.65 (s, 6H, 2ꢀ OCH3 (C3)), 3.67 (s, 6H, 2ꢀ OCH3 (C3)), 3.67 (s,
3H, OCH3 (C3)), 3.72 (m, 1H, H3A), 3.83 (m, 1H, H3), 3.53e3.92 (m,
28H, 4ꢀ H3, 6ꢀ H4, 6ꢀ H5, 6ꢀ H6a, 6ꢀ H6b), 4.65 (dd, 1H, J1,2¼3.1 Hz,
J2,3¼10.3 Hz, H2A), 5.06e5.08 (m, 5H, 5ꢀ H1), 5.13 (d, 1H, J1,2¼3.1 Hz,
4.11. 2A-O-Benzyl-per-O-methyl-
a-cyclodextrin (14)
H1A); 13C NMR (100 MHz, CDCl3):
d 21.01 (CH3CO), 57.74, 57.77,
By the same procedure described in Section 4.4, compound 14
was obtained by flash chromatography (eluent: cyclohexane/
acetone¼2:1) as a white foam in 80% yield. Rf¼0.42 (cyclohexane/
57.84, 57.92 (5C, 5ꢀ OCH3 (C2)), 58.94 (6C, 6ꢀ OCH3 (C6)), 61.18,
61.55, 61.60, 61.72, 61.74, 61.77 (6C, 6ꢀ OCH3 (C3)), 71.11, 71.17, 71.21,
71.33 (6C, 6ꢀ C5), 71.29, 71.40, 71.50, 71.52 (6C, 6ꢀ C6), 74.25 (C2A),
79.55 (C3A), 80.68, 81.15, 81.21, 81.25, 81.37, 81.81, 82.09, 82.12,
82.15, 82.32, 82.39, 82.49 (16C, 5ꢀ C2, 5ꢀ C3, 6ꢀ C4), 99.30 (C1A),
99.96, 100.01, 100.11, 100.22 (5C, 5ꢀ C1), 170.76 (C]O); HRMS calcd
for C55H96NaO31 [MþNa]þ: 1275.5828. Found 1275.5834.
acetone¼3:2); [
CDCl3):
a
]
þ143.2 (c 1.0, CHCl3); 1H NMR (400 MHz,
D
d
3.16e3.21 (m, 5H, 5ꢀ H2), 3.36 (dd, 1H, J1,2¼3.3 Hz,
J2,3¼10.1 Hz, H2A), 3.38 (s, 3H, OCH3 (C6)), 3.39 (s, 3H, OCH3 (C6)),
3.41 (s, 12H, 4ꢀ OCH3 (C6)), 3.49 (s, 9H, 3ꢀ OCH3 (C2)), 3.50 (s, 3H,
OCH3 (C2)), 3.54 (s, 3H, OCH3 (C2)), 3.60 (m, 1H, H3A), 3.63 (s, 3H,
OCH3 (C3)), 3.64 (s, 3H, OCH3 (C3)), 3.65 (s, 3H, OCH3 (C3)), 3.66 (s,
3H, OCH3 (C3)), 3.71 (s, 6H, 2ꢀ OCH3 (C3)), 3.44e3.86 (m, 29H, 5ꢀ
H3, 6ꢀ H4, 6ꢀ H5, 6ꢀ H6a, 6ꢀ H6b), 4.65 (d,1H, Jgem¼12.5 Hz, PhCH2),
4.80 (d, 1H, Jgem¼12.5 Hz, PhCH2), 4.92 (d, 1H, J1,2¼3.3 Hz, H1A),
5.05e5.06 (m, 5H, 5ꢀ H1), 7.24e7.27 (m, 1H, arom-H), 7.31e7.34 (m,
2H, 2ꢀ arom-H), 7.43e7.45 (m, 2H, 2ꢀ arom-H); 13C NMR
4.14. 2A-O-Phenoxythiocarbonyl-per-O-methyl-
a
-cyclodex-
-cyclo-
trin (16) and 2A-O-phenoxycarbonyl-per-O-methyl-
a
dextrin (17)
By the same procedure described in Section 4.6, compound 16
and 17 were obtained by chromatography (eluent: cyclohexane/
acetone¼3:1) as a white foam in 83% and 10% yield, respectively.
(100 MHz, CDCl3):
d
57.79, 57.83, 58.08 (5C, 5ꢀ OCH3 (C2)), 58.88,
58.93 (6C, 6ꢀ OCH3 (C6)), 61.75, 61.95 (6C, 6ꢀ OCH3 (C3)), 71.01,
71.16, 71.18, 71.28 (6C, 6ꢀ C5), 71.40, 71.43 (6C, 6ꢀ C6), 72.16
(PhCH2), 80.01 (C2A), 81.12, 81.20, 81.22, 81.54, 82.06, 82.15, 82.20,
82.39, 82.43, 82.47 (17C, 6ꢀ C2, 6ꢀ C3, 6ꢀ C4), 100.03, 100.07,
100.08, 100.14, 100.31 (5C, 5ꢀ C1), 100.75 (C1A), 127.35, 127.64,
128.17, 138.82 (6C, 6ꢀ arom-C); HRMS calcd for C60H100NaO30
[MþNa]þ: 1323.6192. Found 1323.6183.
Compound 16: Rf¼0.32 (petroleum ether/acetone¼1:1); [
a]
D
þ138.7 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3):
d 3.17e3.21 (m,
5H, 5ꢀ H2), 3.40 (s, 3H, OCH3 (C6)), 3.42 (s, 9H, 3ꢀ OCH3 (C6)), 3.43
(2ꢀ s, 6H, 2ꢀ OCH3 (C6)), 3.50 (2ꢀ s, 6H, 2ꢀ OCH3 (C2)), 3.51 (3ꢀ s,
9H, 3ꢀ OCH3 (C2)), 3.65 (s, 6H, 2ꢀ OCH3 (C3)), 3.66 (s, 3H, OCH3
(C3)), 3.67 (s, 3H, OCH3 (C3)), 3.72 (s, 3H, OCH3 (C3)), 3.73 (s, 3H,
OCH3 (C3)), 3.92 (m, 1H, H3A), 3.53e3.94 (m, 29H, 5ꢀ H3, 6ꢀ H4, 6ꢀ
H5, 6ꢀ H6a, 6ꢀ H6b), 5.06e5.08 (m, 5H, 5ꢀ H1), 5.09 (dd, 1H,
J1,2¼3.5 Hz, J2,3¼9.9 Hz, H2A), 5.50 (d, 1H, J1,2¼3.5 Hz, H1A),
7.18e7.20 (m, 2H, arom-H), 7.29e7.32 (m, 1H, arom-H), 7.41e7.45
4.12. 2A-Hydroxyl-per-O-methyl-
a-cyclodextrin (7)
To a solution of compound 14 (125.7 mg, 0.097 mmol) in
methanol (10 mL) was added 21.2 mg (10%, 0.02 mmol, 0.2 equiv)
of PdeC under nitrogen. The suspension was degassed under
vacuum and urged with H2 three times, then stirred under H2
balloon at room temperature for 16 h. The suspension was filtered
through a pad of Celite and the pad cake was washed with CH3OH
(5 mLꢀ3). The combined filtrate was concentrated to dryness. The
residue was subjected to flash chromatography (eluent: cyclohex-
ane/acetone¼2:1) to give 113.0 mg (97%) of compound 7 as a white
(m, 2H, arom-H); 13C NMR (125 MHz, CDCl3):
d 57.77, 57.79, 57.83,
57.86, 57.99 (5C, 5ꢀ OCH3 (C2)), 58.97 (6C, 6ꢀ OCH3 (C6)), 61.63,
61.71, 61.79, 61.84 (6C, 6ꢀ OCH3 (C3)), 71.18, 71.29, 71.34, 71.38,
71.42, 71.55 (12C, 6ꢀ C5, 6ꢀ C6), 79.67 (C3A), 80.77, 81.15, 81.23,
82.14, 82.26, 82.39, 82.48 (17C, 6ꢀ C2, 5ꢀ C3, 6ꢀ C4), 98.46 (C1A),
100.03, 100.11, 100.16, 100.26, 100.40 (5C, 5ꢀ C1), 122.04, 126.49,
129.48, 153.71 (6C, 6ꢀ arom-C), 195.30 (C]S); HRMS calcd for
C60H98KO31S [MþK]þ: 1385.5439. Found 1385.5405.

4060
S. Xiao et al. / Tetrahedron 69 (2013) 4053e4060
Compound 17: Rf¼0.31 (petroleum ether/acetone¼3:2); [
a
]
Supplementary data
D
þ136.7 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
d 3.18e3.22 (m,
5H, 5ꢀ H2), 3.40 (s, 3H, OCH3 (C6)), 3.42 (s, 9H, 3ꢀ OCH3 (C6)), 3.43
(2ꢀ s, 6H, 2ꢀ OCH3 (C6)), 3.50 (s, 6H, 2ꢀ OCH3 (C2)), 3.51 (s, 6H, 2ꢀ
OCH3 (C2)), 3.52 (s, 3H, OCH3 (C2)), 3.66 (s, 6H, 2ꢀ OCH3 (C3)), 3.67
(s, 6H, 2ꢀ OCH3 (C3)), 3.73 (s, 6H, 2ꢀ OCH3 (C3)), 3.75 (m, 1H, H3A),
3.50e3.90 (m, 29H, 5ꢀ H3, 6ꢀ H4, 6ꢀ H5, 6ꢀ H6a, 6ꢀ H6b), 4.52 (dd,
1H, J1,2¼3.3 Hz, J2,3¼10.1 Hz, H2A), 5.05e5.08 (m, 4H, 4ꢀ H1), 5.10 (d,
1H, J1,2¼3.2 Hz, H1), 5.38 (d, 1H, J1,2¼3.3 Hz, H1A), 7.25e7.27 (m, 3H,
arom-H), 7.38e7.40 (m, 2H, arom-H); 13C NMR (100 MHz, CDCl3):
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.03.070.
References and notes
1. Dodziuk, H. Cyclodextrins and Their Complexes. Chemistry, Analytical Methods,
Applications; Wiley-VCH GmbH & KGaA: Weinheim, Germany, 2006.
2. Schmid, G. In Comprehensive Supramolecular Chemistry; zejtli, J. S., Ed.; Perga-
mon: Oxford, 1996; Vol. 3, p 615.
3. (a) Marcus, E. B. Nat. Rev. Drug Deliv. 2004, 3, 1023e1035; (b) Hashidzume, A.;
Harada, A. Polym. Chem. 2011, 2, 2146e2154; (c) Perchyonok, V.; Oberholzer, T.
Curr. Org. Chem. 2012, 16, 2365e2378.
4. (a) Mosinger, J.; Tomankova, V.; Nemcova, I.; Zyka, J. Anal. Lett. 2001, 34,
1979e2004; (b) Lincoln, S. F.; Pham, D.-T. In Supramolecular Chemistry: From
Molecules to Nanomaterials; Gale, P. A., Steed, J. W., Eds.; 2012; Vol. 3,
pp 954e981; (c) Samakashvili, S.; Salgado, A.; Scriba, G. K. E.; Chankvetadze, B.
Chirality 2013, 25, 79e88.
5. (a) Breslow, R.; Dong, S. D. Chem. Rev. 1998, 98, 1997e2001 and references cited
therein; (b) Bhosale, S. V.; Bhosale, S. V. Mini-Rev. Org. Chem. 2007, 4, 231e242;
(c) Mark, E. D.; Bricout, H.; Hapiot, F.; Ponchel, A.; Tilloy, S.; Monflier, E.
Sustainability 2009, 1, 924e945; (d) Bellia, F.; La-Mendola, D.; Pedone, C.;
Rizzarelli, E.; Saviano, M.; Vecchio, G. Chem. Soc. Rev. 2009, 38, 2756e2781.
6. French, D.; Levine, M. L.; Pazur, J. H.; Norberg, E. J. Am. Chem. Soc. 1949, 71,
353e356.
d
57.81, 57.85, 58.00 (5C, 5ꢀ OCH3 (C2)), 58.97, 58.99 (6C, 6ꢀ OCH3
(C6)), 61.64, 61.73, 61.79, 62.01 (6C, 6ꢀ OCH3 (C3)), 71.20, 71.23,
71.33 (6C, 6ꢀ C5), 71.42, 71.56 (6C, 6ꢀ C6), 78.09 (C2A), 79.66 (C3A),
80.89, 81.21, 81.28, 82.17, 82.27, 82.39, 82.45, 82.52, 82.56 (16C, 5ꢀ
C2, 5ꢀ C3, 6ꢀ C4), 99.43 (C1A), 100.07, 100.11, 100.17, 100.21, 100.42
(5C, 5ꢀ C1), 121.26, 126.04, 129.46, 153.63 (6C, 6ꢀ arom-C), 151.22
(C]O); HRMS calcd for C60H98NaO32 [MþNa]þ: 1353.5933. Found
1369.5944.
4.15. 2A-Deoxy-per-O-methyl-
a-cyclodextrin (18)
By the same procedure described in Section 4.7, compound 18 was
obtained by chromatography (eluent: CH2Cl2/CH3OH¼30:1e20:1) as
7. Chatjigakis, A. K.; Donze, C.; Coleman, A. W. Anal. Chem. 1992, 64, 1632e1634.
8. (a) Bergeron, A. R.; Machida, Y.; Bloch, K. J. Biol. Chem. 1975, 250, 1223e1230; (b)
Casu, B.; Reggiani, M.; Sanderson, G. R. Carbohydr. Res. 1979, 76, 59e66; (c)
Szejtli, J. In Cyclodextrins and Their Inculsion Complexes; Akademiai Kiado:
Budapest, 1982.
a white foam in 74% yield. Rf¼0.29 (CH2Cl2/CH3OH¼15:1); [
a]
D
ꢀ
ꢀ
þ143.5 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
d 1.65e1.71 (m, 1H,
H2aA), 2.27e2.32 (m,1H, H2bA), 3.15e3.19 (m, 5H, 5ꢀ H2), 3.40 (s, 3H,
OCH3 (C6)), 3.41 (s,15H, 5ꢀ OCH3 (C6)), 3.47 (s, 3H, OCH3 (C2)), 3.48 (s,
3H, OCH3 (C2)), 3.49 (s, 6H, 2ꢀ OCH3 (C2)), 3.50 (s, 3H, OCH3 (C2)), 3.53
(s, 3H, OCH3 (C3)), 3.63 (s, 3H, OCH3 (C3)), 3.64 (2ꢀ s, 9H, 3ꢀ OCH3
(C3)), 3.74 (m, 1H, H3A), 3.51e3.89 (m, 29H, 5ꢀ H3, 6ꢀ H4, 6ꢀ H5, 6ꢀ
H6a, 6ꢀ H6b), 5.02 (t, 1H, J1,2¼2.4 Hz, H1A), 5.04e5.07 (m, 5H, 5ꢀ H1);
9. (a) Chaise, T.; Bourgeaux, E.; Cardinael, P.; Combret, J. C. Tetrahedron Lett. 2004,
45, 5853e5856; (b) Akira, K.; Toshiyuki, K.; Yohji, N.; Mitsuru, A. J. Org. Chem.
2005, 70, 1253e1261; (c) Bsch, A.; Mischnick, P. Biomacromolecules 2007, 8,
2311e2320; (d) Favrelle, A.; Bonnet, V.; Sarazin, C.; Djedaini-Pilard, F.
Tetrahedron: Asymmetry 2008, 19, 2240e2245; (e) Gan, Y. J.; Zhang, Y. M.; Xiao,
C. H.; Zhou, C. Y.; Zhao, Y. C. Carbohydr. Res. 2011, 346, 389e392; (f) Kitagishi, H.;
Kashiwa, K.; Kano, K. Biopolymers 2012, 97, 11e20.
ꢀ
ꢀ
10. (a) Szejtli, J. In Cyclodextrins and Their Inculsion Complexes; Akademiai Kiado:
Budapest, 1982; (b) Khan, A. R.; Forgo, P.; Stine, K. J.; D’Souza, V. T. Chem. Rev.
1998, 98, 1977e1996 and references cited therein; (c) Chaise, T.; Cardinael, P.;
Tisse, S.; Combret, J. C.; Bouillon, J. P. Tetrahedron: Asymmetry 2008, 19,
348e357; (d) Di-Fabio, G.; Malgieri, G.; Isernia, C.; D’Onofrio, J.; Gaglione, M.;
Messere, A.; Zarrelli, A.; De Napoli, L. Chem. Commun. 2012, 3875e3877.
13C NMR (100 MHz, CDCl3):
d
35.49 (C2A), 57.57, 57.79, 57.83, 57.94
(6C, 6ꢀ OCH3 (C3)), 58.73, 58.96, 59.00, 59.02 (6C, 6ꢀ OCH3 (C6)),
61.20, 61.74, 61.78, 61.81 (5C, 5ꢀ OCH3 (C2)), 70.99, 71.10, 71.16, 71.21,
71.34, 71.96 (6C, 6ꢀ C5), 71.31, 71.39, 71.44, 71.98 (6C, 6ꢀ C6), 77.47
(C3A), 80.96, 81.25, 81.40, 81.71, 82.10, 82.14, 82.19, 82.23, 82.35, 82.47
(16C, 5ꢀ C2, 5ꢀ C3, 6ꢀ C4), 99.49, 99.85, 99.93, 100.13, 100.33 (5C, 5ꢀ
C1), 101.84 (C1A); HRMS calcd for C62H110NaO34 [MþNa]þ: 1217.5773.
Found 1217.5772.
€
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Financial support of this study from CNRS and the University
Pierre & Marie Curie (program of LIA), the National Basic Research
Program of China (973 Program; grant no. 2010CB12300) and the
National Natural Science Foundation of China (grant nos. 20932001
and 20852001) are gratefully acknowledged. The authors express
their gratitude to Cyclolab (Hungary) for a generous supply of
starting material. S.X. thanks the China Scholarship Council for
a Ph.D. fellowship.
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