Effective synthesis of negatively charged cyclodextrins. Selective access to phosphate cyclodextrins

Article abstract of DOI:10.1016/j.tet.2008.05.094

We report the selective preparation of α- and β-cyclodextrins bearing one and two phosphate moieties on the primary rim. These compounds were prepared by selective O-debenzylation of fully protected derivatives, followed by phosphorylation and deprotection. The synthesis of an α-cyclodextrin with both, a carboxylic group and a phosphate moiety on primary positions is also described. Title compounds are examples of negatively charged cyclodextrins that might be of interest in studying the complexation of cationic guests.

Full text of DOI:10.1016/j.tet.2008.05.094

Tetrahedron 64 (2008) 7587–7593
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Effective synthesis of negatively charged cyclodextrins. Selective access
to phosphate cyclodextrins
a
,
b,
*
´
a
*
´
Oscar Lopez , Mikael Bols
´
´
Departamento de Qu´ımica Organica, Facultad de Quımica, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain
b Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Kbh. Ø, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 April 2008
Received in revised form 16 May 2008
Accepted 20 May 2008
Available online 23 May 2008
We report the selective preparation of a- and b-cyclodextrins bearing one and two phosphate moieties
on the primary rim. These compounds were prepared by selective O-debenzylation of fully protected
derivatives, followed by phosphorylation and deprotection. The synthesis of an -cyclodextrin with both,
a
a carboxylic group and a phosphate moiety on primary positions is also described. Title compounds are
examples of negatively charged cyclodextrins that might be of interest in studying the complexation of
cationic guests.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Reaction was shown to proceed faster when increasing the
phosphate buffer concentration, and the proposed mechanism
Supramolecular chemistry is emerging as a challenging area in
organic chemistry; the study of derivatives capable of establishing
spontaneous non-covalent interactions is of great interest and has
found many practical applications such as additives for food pres-
ervation,1 drug delivery,2,3 catalysis,4,5 biomimetic recognition6 and
chiral separations.7 In this context, cyclodextrins, cyclic oligosac-
involves the cyclodextrin-mediated stabilization of the incipient
positive charge in the transition state, followed by nucleophilic
displacement of the aglycon by a phosphate molecule of the buffer.12
This observation prompted us to prepare cyclodextrin derivatives
bearing phosphate moieties in their structure, with the aim of
studying the same hydrolysis reaction and to compare with isosteric
carboxylic acid and sulfate derivatives 1–3 in order to determine
whether the phosphate moiety can participate in the catalytic pro-
cess. Thus,phosphorylatedcyclodextrinsmightmimicthebehaviour
of phosphorylases, which catalyze the hydrolysis and/or transfer of
glycosides through a phosphate group attached to pyridoxal.13–16
Furthermore, cyclodextrins incorporating ionizable groups rep-
resent an interesting family of maltooligosaccharides for complexing
charged guests in aqueous media through attractive Coulombic in-
teractions.17 For instance, the use of a monophosphate cyclodextrin
has been used by Cho et al.18 for binding antineoplastic drugs and
subsequent release of the guest upon phoshatase-mediated hydro-
lysis. Anioniccyclodextrinssuchasphosphates, carboxylates, sulfates
or succinylates have been studied as additives for plant growth ac-
celeration and for the release of essential nutrients.19 Charged cy-
clodextrins also allow an improvement of the isolation of plant
metabolites;inthiscontext, strongnon-covalentcomplexesbetween
cyclodextrins and anticarcinogenic taxol and other taxanes have
been reported, what led to higher amounts of the isolated product.19
charides of six, seven or eight a-D-glucopyranose units are among
the most important molecular hosts considered in supramolecular
chemistry.8 Numerous chemical9–11 and enzymatic synthesis8 of
cyclodextrin derivatives have been reported so far; nevertheless,
chemical modification of cyclodextrins is not a simple task due to
the high number of hydroxyl groups present in these structures.
In this context, we have recently reported12 the preparation of
cyclodextrin-derived 6A,6D-diacids 1 and 2, as well as 6A,6D-di-O-
sulfate 3 as novel artificial enzymes, which accelerated the hydrolysis
of aryl glycosides in a phosphate buffered medium up to 989 times.
O
O
HO
OH
S
S
O
O
O
O
O
O
HO
OH
α,β
(OH)n
(OH)19
1
2
n=16
n=19
3
2. Results and discussion
Ubiquitous organophosphorous derivatives are extremely im-
portant derivatives in biological systems and exhibit practical
* Corresponding authors.
E-mail addresses: osc-lopez@us.es (O. Lopez), bols@kemi.ku.dk (M. Bols).
´
´
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.094

´
O. Lo´pez, M. Bols / Tetrahedron 64 (2008) 7587–7593
7588
applications such as chiral discriminators or membrane car-
riers;20,21 however, reports on their use in supramolecular chem-
istry is relatively scarce. Breslow’s group accomplished22 the
Nevertheless, DMAP-promoted phosphorylation of diols 8 and 9
with commercial chlorodiphenylphosphate in pyridine afforded
diphosphorylated derivatives 10 and 11, in 87% and 86% yields,
respectively, after chromatography. The presence of the phosphate
moiety was supported by NMR spectroscopy; 13C NMR spectra of
compounds 10 and 11 showed coupling between phosphorus and
synthesis of the ammonium salt of b-cyclodextrin monophosphate
by treatment of unprotected cyclodextrin with diphenyl-
chlorophosphate; the corresponding phosphate ester was purified
by a tedious series of crystallizations and hydrogenated under
pressure to afford final compound in moderate yield. The same
derivative was later re-studied18 and partially characterized by
Eliseev’s group. Tarelli and co-workers described23 treatment of
2
ipso carbons on aromatic phosphate ester residues with a JP,C of
4.0–6.5 Hz. 31P NMR spectrum of
a-cyclodextrin diphosphate 10
showed a singlet signal at ꢀ10.8 ppm; on the other hand, 31P NMR
spectrum of compound 11 showed two non-equivalent phosphate
groups at ꢀ10.7 and ꢀ10.8 ppm.
a
- and b-cyclodextrin with inorganic metaphosphate to afford a
mixture of isomeric monophosphates on positions 2, 3 and 6, which
were partially resolved by anion-exchange chromatography.
Branched cyclodextrin triphosphates were prepared using either
Phosphate esters could neither be deprotected under standard
hydrogenation conditions nor basic hydrolysis. Fully unprotected
derivatives 12 and 13 were achieved by first removal of the benzyl
ether groups by Pd-catalyzed hydrogenation, followed by Pt-cata-
lyzed hydrogenation at moderate pressure (20 atm). Filtration and
removal of the solvents afforded pure 12 and 13 in 60% and 83%
yields, respectively. 31P NMR spectra of these cyclodextrin di-
phosphates showed a singlet signal at 1.7 and 1.3 ppm, respectively,
in accordance with reported primary phosphate groups on
carbohydrates.18,45
cyclo-mono-
m
-imidotriphosphate (c-MITP)24 or cyclo-triphosphate
(P3m).25 Liu et al. reported26 the use of phosphoryl-tethered
b
-
cyclodextrins as an enhancement of the chiral recognition ability of
maltooligosaccharides. The use of cyclodextrin monophosphate
esters for complexing aminoacids27 and organic dyes28 has also
been reported.
We have synthesized cyclodextrins bearing two phosphate
groups on primary positions starting from
a- and
b
-cyclodextrins
Following a similar procedure, we have also prepared cyclo-
(Scheme 1); the starting materials are partially debenzylated cy-
clodextrins, which are accessed using a straightforward procedure,
originally introduced by Sinay¨’s group for the selective and mild
deprotection of benzylated29 or methylated30 derivatives. This
procedure involves treatment of fully protected derivatives with
DIBAL-H in anhydrous toluene; the original synthetic conditions
were later optimized,12,31–33 mainly by Sinay¨’s group in subsequent
technical improvements. Selectively debenzylated cyclodextrins
have been widely used in our group for the preparation of artificial
enzymes based on cyclodextrins for catalyzing glycoside hydrolysis
of amine oxidation.12,34–43
dextrin-derived monophosphates starting from a- and b-cyclo-
dextrin (Scheme 2). Treatment of per-O-benzylated cyclodextrins 6
and 7 with fewer equivalents of DIBAL-H, and shorter reaction
times afforded monodeprotected derivatives 14 and 15 that fur-
nished protected monophosphates 16 and 17 upon reaction with
chlorodiphenylphosphate, using the same conditions as indicated
above. These compounds showed coupling between ipso aromatic
carbons and phosphorous (2JP,C¼6.5 Hz) and resonance at
ꢀ10.7 ppm in 31P NMR spectra. Standard hydrogenation, followed
with Pt-catalyzed hydrogenation at 20 atm afforded fully un-
protected derivatives 18 and 19 in 79% and 71% yields, respectively.
Initial attempts to transform diols 8 and 9 into the corre-
sponding diphosphates using classical phosphate syntheses were
We also describe the preparation of an a-cyclodextrin derivative
bearing a phosphate and a carboxylic acid moiety in the same
molecule (Scheme 3). The key step for this synthesis is the
unsuccessful; thus, reaction of a-cyclodextrin diol 8 with dibenzyl
N,N-diisopropylamino phosphoramidate44 in the presence of tet-
razole, followed by oxidation with iodide resulted in decomposition
to a mixture of more polar derivatives.
monoprotection of a-cyclodextrin diol 8 with allyl bromide in
t
the presence of BuOK.46 Derivative 20 was phosphorylated using
the same conditions as indicated in Schemes 1 and 2; removal of
HO
OH
D
A
BnCl
DIBAL-H, toluene
4 Å MS, rt, N2
α,β
α,β
α,β
NaH, DMSO
N2, rt, overnight
(OH)n
(OBn)n
(OBn)n
8
9
n=16
n=19
4
n=18
n=21
6
n=18
5
7 n=21
O
P
OPh
OPh
Cl
DMAP
Py, N2
O
P
O
O
P
O
HO
HO
PhO
PhO
OPh
OPh
OH
OH
P
P
O
O
O
O
D
A
D
A
1) H2, Pd/C
1:1 EtOAc−MeOH
α,β
α,β
2) H2, PtO2
1:1 MeOH−H2O
(OH)n
(OBn)n
12 n=16
13 n=19
10 n=16
11 n=19
Scheme 1.

´
O. Lo´pez, M. Bols / Tetrahedron 64 (2008) 7587–7593
7589
HO
the allyl group of 21 was achieved by first isomerization with
Wilkinson’s catalyst, followed by in situ generated acid treatment
to afford 22.
DIBAL-H,toluene
4 ÅMS, rt, N2
α,β
α β
,
The free hydroxyl group on 22 was first oxidized to the corre-
sponding aldehyde by using Dess–Martin periodinane, followed by
further oxidation to the carboxylic acid moiety with NaClO2 in
47
(OBn)n
(OBn)n
a buffered medium to afford protected derivative 23. Final depro-
tection of 23 using the same conditions as for mono- and di-
phosphate derivatives (Schemes 1 and 2) afforded 24, a novel
cyclodextrin derivative bearing two different acidic moieties on
primary positions (Scheme 3).
14 n=17
15 n=20
6
7
n=18
n=21
O
P
OPh
OPh
Cl
Fully unprotected derivatives 12, 13, 18, 19 and 24 were tested
for catalysis in hydrolysis reactions of aryl glycosides and of aryl
phosphates at different pH values and temperatures. Surprisingly,
title compounds did not show appreciable catalysis. A possible
explanation is the different solvation properties exhibited by carb-
oxylates, sulfates and phosphates. Calculated12 pKa values for di-
acids 1 and 2 turned out to be 3.5 and 3.2, respectively. On the other
hand, the reported48 pKa’s values for glucose-6-phosphate are 0.94
and 6.11. These data suggest that phosphate derivatives bear
a larger negative charge than carboxylates and sulfates. Further-
more, thermodynamics data49 for solvation of lithium and sodium
salts of carboxylates, sulfates and phosphates indicate a significant
stabilization of the latter in aqueous medium. This might lead to
a prominent decrease of the stabilization of the incipient positive
charge in the aryl glycoside hydrolysis transition state exerted by
the cyclodextrin. Furthermore, a more solvated derivative might
DMAP
Py, N2
O
O
OH
OH
OPh
OPh
P
P
O
O
1) H2, Pd/C
1:1 EtOAc−MeOH
α,β
α,β
2) H2, PtO2
1:1 MeOH−H2O
(OH)n
(OBn)n
n=17
18
16
17
n=17
n=20
19
n=20
Scheme 2.
HO
O
HO
OH
O
OBn
Cl
P
D
A
D
A
t
OBn
DMAP, Py
N2
1) BuOK, TFH, N2 30 min
α
α
2) Allyl bromide, n-BuNI
THF, N2, overnight
(OBn)16
(OBn)16
20
8
O
P
O
OBn
OBn
OBn
P
OBn
O
O
OH
O
1) Wilkinson´s catalyst, DABCO
7:3 EtOH−Toluene, reflux
D
A
D
A
2) AcCl, 2:1 CH2Cl2−MeOH
α
α
(OBn)16
(OBn)16
22
21
1) Dess-Martin periodinane
CH2Cl2
2) NaClO2, NaH2PO4,
2-methylbut-2-ene
t
BuOH−THF−H2O
O
O
P
OBn
P
OH
OH
OBn
O
O
O
O
HO
D
HO
1) H2, Pd/C
A
D
A
1:1 EtOAc−MeOH
α
α
2) H2, PtO2
1:1 MeOH−H2O
(OBn)16
(OH)16
23
24
Scheme 3.

´
O. Lo´pez, M. Bols / Tetrahedron 64 (2008) 7587–7593
7590
also involve a more crowded system for complexing the aromatic
residue of the glycoside, and thus, a reduced capacity of the cy-
clodextrin for establishing inclusion complexes.
(1.54 mL, 7.38 mmol) at 0 ꢁC under N2. The corresponding solution
was kept stirring overnight and after that it was poured over
water–ice. Dichloromethane was added (120 mL) and the organic
phase was washed with 1 M HCl (3ꢂ70 mL), satd aq NaHCO3
(1ꢂ70 mL), H2O (1ꢂ70 mL), dried over Na2SO4, filtered and con-
centrated to dryness. The residue was purified by column chro-
matography (pentane/1:2 EtOAc–pentane) to afford title
In conclusion, wehave developed aversatile methodology for the
successful preparation of phosphate-containing cyclodextrins,
compounds of high practical and biological interest. For this pur-
pose, we have combined the practical and selective de-O-benzyla-
tion of fully benzylated cyclodextrins and phosphorylation with
diphenylphosphoryl chloride. Although the final derivatives did not
show appreciable catalysis in the aryl glycosides hydrolysis, they
comprise a family of valuable chiral tools for the complexation of
positively charged guests. These negatively charged cyclodextrins
are obtained in a selective fashion that avoids mixtures of phosphate
regioisomers as described in other procedures in the literature, and
subsequent difficult purifications.
compound (1.51 g, 86%).
23
[
a
]
þ45 (c 0.4, CH2Cl2); 1H NMR (400 MHz, CDCl3):
d 7.21–6.98
D
(m, 115H, Ar–H), 5.30 (d, 1H, J1,2¼3.6 Hz, H-1), 5.18 (d, 1H,
J1,2¼3.6 Hz, H-1), 5.14 (d, 1H, J1,2¼3.6 Hz, H-1), 5.11 (d, 1H,
J1,2¼3.2 Hz, H-1), 5.09 (d, 1H, J1,2¼3.5 Hz, H-1), 5.11–5.05 (m, 4H),
5.02 (d, 1H, J1,2¼4.00 Hz, H-1), 4.93–4.88 (m, 3H, JH,H¼10.0 Hz, CH),
4.76–4.69 (m, 7H), 4.55–4.23 (m, 22H), 4.01–3.91 (m, 24H), 3.84 (d,
1H, JH,H¼8.8 Hz), 3.82 (d, 1H, JH,H¼11.2 Hz), 3.79 (d, 1H,
JH,H¼10.8 Hz), 3.77 (d, 1H, JH,H¼9.2 Hz), 3.69 (d, 1H, JH,H¼10.8 Hz),
3.62 (d, 1H, JH,H¼10.4 Hz), 3.51–3.41 (m, 9H), 3.27 (dd, 3H,
J2,3¼9.6 Hz, H-2), 3.23 (dd, 3H, J2,3¼9.6 Hz, H-2); 13C NMR
3. Experimental section
3.1. General
(100 MHz, CDCl3):
d
150.7 (d, JC,P¼4.0 Hz, Cipso phosphate), 150.6 (d,
JC,P¼5.0 Hz, Cipso phosphate), 150.5 (d, JC,P¼7.0 Hz, Cipso phosphate),
139.4, 139.2, 138.5, 138.4, 138.3, 138.2 (Cipso), 129.9, 129.7, 128.4,
128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.6, 127.5, 127.4, 127.3, 127.1
(CHAr), 125.3, 120.2, 120.1, 120.0 (CHAr–phosphate), 98.9, 98.8, 98.5,
98.4, 98.3 (C-1), 81.0, 80.8, 80.7, 80.4, 79.3, 79.2, 79.1, 78.8, 78.6, 77.7,
75.8, 75.7, 75.5, 75.4, 75.1, 73.6, 73.4, 73.2, 72.9, 72.7, 72.6, 72.0, 71.6,
71.5, 70.8, 70.7, 70.6, 70.4, 69.4, 68.5, 68.1, 60.5; 31P NMR
Solvents were distilled under anhydrous conditions. All reagents
wereusedaspurchasedwithoutfurtherpurification. Evaporationwas
carried out in a rotatory evaporator. Glassware used for water-free
reactions was dried for 2 h at 130 ꢁC before use. Columns were packed
with silica gel 60 (230–400 mesh) as the stationary phase. TLC plates
(Merck 60 F254) were visualized by spraying with cerium sulfate (1%)
and molybdic acid (1.5%) in 10% H2SO4 and heating until coloured
spots appeared. 1H, 13C NMR and COSY experiments were carried out
with a Varian Mercury 400 instrument. Monoisotopic mass spectra
(MALDI-TOF MS) were obtained on a Bruker Daltonics mass spec-
(161.9 MHz, CDCl3):
3332.3094; found: 3332.2608.
d
ꢀ10.7, ꢀ10.8; MS: calcd for C199H202NaO41P2:
3.4. 6A,6D-Di-O-phosphate-
a-cyclodextrin (12)
trometer using an
a-cyanohydroxycinnamic acid (a-CHCA) matrix.
Spectra were calibrated using a peptide calibration standard solution.
Compound 10 (0.80 g, 0.29 mmol) was dissolved in 1:1 MeOH–
EtOAc (20 mL). Then, Pd–C (320 mg) and TFA (cat.) were added and
the mixture was kept stirring under hydrogen atmosphere for 3
days. Filtration and removal of the solvents afforded intermediate
3.2. 6A,6D-Di-O-(diphenylphosphate)-hexadeca-O-benzyl-
a-
cyclodextrin (10)
6A,6D-di-O-(diphenylphosphate)-
a-cyclodextrin. This compound
To a solution of diol 8 (1.00 g, 0.41 mmol) and DMAP (15 mg,
0.12 mmol) in Py (10 mL) was added diphenylphosphoryl chloride
(1.03 mL, 4.97 mmol) at 0 ꢁC under N2. The corresponding solution
was kept stirring overnight and after that it was poured over water–
ice. Dichloromethanewasadded(100 mL)andtheorganicphasewas
washed with 1 M HCl (3ꢂ50 mL), satd aq NaHCO3 (1ꢂ50 mL), H2O
(1ꢂ50 mL), dried over Na2SO4, filtered and concentrated to dryness.
The residue was purified bycolumn chromatography (pentane/1:3
was dissolved in 1:1 MeOHꢀH2O (20 mL), and to the solution was
added PtO2 (232 mg); the corresponding mixture was vigorously
stirred under hydrogen atmosphere (20 atm) for 3 days. Filtration
and removal of the solvents furnished title compound (194 mg,
60%).
23
[
a
]
þ101 (c 0.4, H2O); 1H NMR (400 MHz, D2O):
d 5.05–5.01 (m,
D
6H, H-1), 4.12 (m, 2H), 3.94–3.92 (m, 10H), 3.81 (m, 9H), 3.59–3.54
(m, 17H); 13C NMR (100 MHz, DMSO-d6):
83.3, 82.7, 82.5, 73.9, 73.4, 73.2, 73.1, 72.5, 72.3, 72.1, 72.0, 70.7, 65.2,
60.4; 31P NMR (161.9 MHz, D2O):
1.7; MS: calcd for
36H60Na3O36P2: 1199.2033; found: 1198.3985.
d 102.3, 101.6, 101.2 (C-1),
EtOAc–pentane) to afford title compound (988 mg, 87%).
23
[a
]
þ36 (c 1.4, CH2Cl2); 1H NMR (400 MHz, CDCl3):
d
7.31–7.12
d
D
(m, 100H, Ar–H), 5.32 (d, 2H, JH,H¼10.8 Hz, CH), 5.25 (d, 2H,
J1,2¼3.2 Hz, H-1), 5.15–5.12 (m, 5H, J1,2¼3.2 Hz, JH,H¼10.0 Hz, H-1,
CH), 5.00 (d, 2H, J1,2¼3.1 Hz, H-1), 4.94–4.86 (m, 8H, CH), 4.56 (d,
1H, JH,H¼12.4 Hz, CH), 4.49–4.42 (m, 17H), 4.37–4.32 (m, 5H), 4.20–
4.02 (m, 13H), 3.98–3.96 (m, 10H), 3.63 (m, 2H), 3.54–3.47 (m, 5H),
C
3.5. 6A,6D-Di-O-phosphate-
b-cyclodextrin (13)
Compound 11 (1.50 g, 0.45 mmol) was dissolved in 1:1
MeOHꢀEtOAc (20 mL). Then, Pd(OH)2 (356 mg) and TFA (cat.) were
added and the mixture was kept stirring under hydrogen atmo-
sphere for 2 days. Filtration and removal of the solvents afforded
3.34 (dd, 2H, J¼3.6, 9.6 Hz); 13C NMR (100 MHz, CDCl3):
d 150.7 (d,
JC,P¼6.5 Hz, Cipso phosphate), 150.6 (d, JC,P¼7.0 Hz, Cipso phosphate),
139.4, 138.4, 138.3, 138.2, 138.1 (Cipso), 129.8, 128.4, 128.3, 128.1,
128.0, 127.7, 127.6, 127.5, 127.3, 127.2, 127.1 (CHAr), 125.4, 125.3,
120.3, 120.2, 120.1 (CHAr–phosphate), 99.0, 98.7, 98.6 (C-1), 81.2,
80.7, 80.5, 80.4, 79.6, 79.3, 79.2, 78.4, 78.1, 76.0, 75.7, 75.3, 73.6, 73.5,
73.0, 72.7, 72.1, 71.6, 70.9, 70.8, 69.2, 69.0, 68.5, 60.6; 31P NMR
intermediate 6A,6D-di-O-(diphenylphosphate)-
b-cyclodextrin. This
compound was dissolved in 1:1 MeOH–H2O (40 mL), and to the
solution was added PtO2 (291 mg); the corresponding mixture was
vigorously stirred under hydrogen atmosphere (20 atm) for 3 days.
Filtration and removal of the solvents furnished title compound
(161.9 MHz, CDCl3):
2900.1158; found: 2899.3690.
d
ꢀ10.8; MS: calcd for C172H174NaO36P2:
(482 mg, 83%).
23
[
a
]
D
þ104 (c 0.4, H2O); 1H NMR (400 MHz, D2O):
d 5.13–5.10 (m,
3.3. 6A,6D-Di-O-(diphenylphosphate)-nonadeca-O-benzyl-
b-
7H, H-1), 4.19 (m, 2H), 4.01–3.91 (m, 23H), 3.69–3.61 (m, 17H); 13
C
cyclodextrin (11)
NMR (100 MHz, DMSO-d6):
82.9, 82.8, 82.7, 82.6, 82.5, 82.4, 74.6, 73.4, 72.5, 72.4, 65.4, 65.3, 61.7,
61.6; 31P NMR (161.9 MHz, D2O):
1.3; MS: calcd for
42H70Na3O41P2: 1361.2561; found: 1360.3671.
d 103.5, 103.4, 103.3, 103.2 (C-1), 83.0,
To a solution of diol 9 (1.50 g, 0.53 mmol) and DMAP (64 mg,
0.53 mmol) in Py (15 mL) was added diphenylphosphoryl chloride
d
C

´
O. Lo´pez, M. Bols / Tetrahedron 64 (2008) 7587–7593
7591
3.6. 6A-O-(Diphenylphosphate)-heptadeca-O-benzyl-
a
-
intermediate
6A-O-(diphenylphosphate)-
a-cyclodextrin.
This
cyclodextrin (16)
compound was dissolved in 1:1 MeOH–H2O (30 mL), and to the
solution was added PtO2 (192 mg); the corresponding mixture was
vigorously stirred under hydrogen atmosphere (20 atm) for 3 days.
Filtration and removal of the solvents furnished title compound
To a solution of derivative 14 (0.71 g, 0.29 mmol) and DMAP
(20 mg, 0.16 mmol) in Py (7 mL) was added diphenylphosphoryl
chloride (0.60 mL, 2.88 mmol) at 0 ꢁC under N2. The corresponding
solution was kept stirring overnight and after that it was poured
over water–ice. Dichloromethane was added (125 mL) and the or-
ganic phase was washed with 1 M HCl (2ꢂ50 mL), satd aq NaHCO3
(1ꢂ50 mL), H2O (1ꢂ50 mL), dried over Na2SO4, filtered and con-
centrated to dryness. The residue was purified by column chro-
matography (pentane/1:3 EtOAc-pentane) to afford title
(196 mg, 79%).
23
[a
]
þ103 (c 0.4, H2O); 1H NMR (400 MHz, D2O):
d 5.06–5.02
D
(m, 6H, H-1), 4.13 (m, 2H), 3.97–3.80 (m, 20H), 3.61–3.55 (m, 14H);
13C NMR (100 MHz, DMSO-d6):
82.5, 82.4, 82.3, 82.1 73.6, 73.3, 73.2, 72.3, 72.2, 72.1, 71.8, 60.1; 31
NMR (161.9 MHz, D2O): 2.3; MS: calcd for C36H60Na2O33P:
1097.2550; found: 1096.5359.
d
102.1 (ꢂ2) 102.0, 101.9 (C-1), 82.6,
P
d
compound (731 mg, 91%).
23
[
a]
þ38 (c 0.5, CH2Cl2); 1H NMR (400 MHz, CDCl3):
d 7.27–7.09
D
3.9. 6A-O-Phosphate-
b-cyclodextrin (19)
(m, 95H, Ar–H), 5.26 (d, 1H, JH,H¼10.0 Hz, CH), 5.24 (d, 1H,
JH,H¼11.2 Hz, CH), 5.22 (d, 1H, JH,H¼10.8 Hz, CH), 5.17–5.12 (m, 6H),
5.09 (d, 1H, J1,2¼3.6 Hz, H-1), 5.05 (d, 1H, J1,2¼3.6 Hz, H-1), 5.01 (d,
1H, J1,2¼3.2 Hz, H-1), 4.89–4.84 (m, 7H), 4.54–4.40 (m,17H), 4.40 (d,
1H, JH,H¼11.6 Hz, CH), 4.37 (d, 1H, JH,H¼11.6 Hz, CH), 4.36 (d, 1H,
JH,H¼12.0 Hz, CH), 4.32 (d, 1H, JH,H¼11.6 Hz, CH), 4.30 (d, 1H,
JH,H¼13.2 Hz, CH), 4.27 (d, 1H, JH,H¼12.0 Hz, CH), 4.06–3.88 (m,
22H), 3.62 (d, 2H, JH,H¼10.8 Hz), 3.54–3.44 (m, 8H), 3.27 (dd, 2H,
Compound 17 (0.53 g, 0.17 mmol) was dissolved in 1:1 MeOH–
EtOAc (20 mL). Then, Pd(OH)2 (298 mg) and TFA (cat.) were added
and the mixture was kept stirring under hydrogen atmosphere for
2
days. Filtration and removal of the solvents afforded in-
termediate 6A-O-(diphenylphosphate)-
b-cyclodextrin. This com-
pound was dissolved in 1:1 MeOH–H2O (20 mL), and to the
solution was added PtO2 (120 mg); the corresponding mixture was
vigorously stirred under hydrogen atmosphere (20 atm) for 3 days.
Filtration and removal of the solvents furnished title compound
J1,2¼3.2 Hz, J2,3¼10.0 Hz, H-2); 13C NMR (100 MHz, CDCl3):
d 150.7
(d, JC,P¼6.5 Hz, Cipso phosphate), 150.7 (d, JC,P¼6.5 Hz, Cipso phos-
phate), 139.5, 139.4, 138.5, 138.4, 138.3, 138.2 (Cipso), 129.9, 129.8,
128.4, 128.3, 128.1, 127.8, 127.7, 127.5, 127.4, 127.1 (CHAr), 125.4 125.3
(CHAr–phosphate), 99.0, 98.9, 98.8, 98.7, 98.6 (C-1), 81.2, 81.1, 80.8,
80.6, 79.8, 79.7, 79.5, 79.3, 79.2, 79.1, 78.8, 78.6, 75.8, 75.6, 75.5,
73.6, 72.8, 72.1, 71.7, 71.6, 70.7, 69.3, 69.1, 68.3; 31P NMR (161.9 MHz,
(146 mg, 71%).
23
[a
]
þ115 (c 0.3, H2O); 1H NMR (400 MHz, D2O):
d 5.14–5.10 (m,
D
7H, H-1), 4.15 (m, 2H), 4.02–3.88 (m, 25H), 3.72–3.59 (m, 14H)
(lit.18); 13C NMR (100 MHz, DMSO-d6):
82.6, 82.0, 81.3, 81.0, 72.6, 71.9, 71.5, 71.4, 60.4, 59.9, 59.4, 59.3; 31
NMR (161.9 MHz, DMSO-d6): 0.16; MS: calcd for C42H70Na2O38P:
1259.3078; found: 1258.5734.
d 101.8, 101.5, 101.4, 101.3,
P
CDCl3):
2758.7788.
d
ꢀ10.7; MS: calcd for C167H171NaO33P2: 2758.1338; found:
d
3.7. 6A-O-(Diphenylphosphate)-eicosa-O-benzyl-
b-
cyclodextrin (17)
3.10. 6A-O-allyl-6D-O-(Diphenylphosphate)-hexadeca-O-
benzyl- -cyclodextrin (21)
a
To a solution of derivative 15 (0.70 g, 0.24 mmol) and DMAP
(23 mg, 0.19 mmol) in Py (7 mL) was added diphenylphosphoryl
chloride (0.50 mL, 2.38 mmol) at 0 ꢁC under N2. The corresponding
solution was kept stirring overnight and after that it was poured
over water–ice. Dichloromethane was added (125 mL) and the or-
ganic phase was washed with 1 M HCl (2ꢂ50 mL), satd aq NaHCO3
(1ꢂ50 mL), H2O (1ꢂ50 mL), dried over Na2SO4, filtered and con-
centrated to dryness. The residue was purified by column chro-
matography (pentane/1:3 EtOAc–pentane) to afford title
To a solution of 6A-O-allyl-hexadeca-O-benzyl-
a-cyclodextrin
20 (0.59 g, 0.24 mmol) and DMAP (31 mg, 0.25 mmol) in Py (5 mL)
was added diphenylphosphoryl chloride (0.35 mL, 1.69 mmol) at
0 ꢁC under N2. The corresponding solution was kept stirring over-
night and after that it was poured over water–ice. Dichloromethane
was added (150 mL) and the organic phase was washed with 1 M
HCl (2ꢂ50) mL, satd aq NaHCO3 (1ꢂ50 mL), H2O (1ꢂ50 mL), dried
over Na2SO4, filtered and concentrated to dryness. The residue was
purified by column chromatography (pentane/1:3.5 EtOAc–pen-
compound (620 mg, 82%).
23
[
a]
þ46 (c 1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3):
d
7.30–7.06
tane) to afford title compound (574 mg, 88%).
D
þ37 (c 1.2, CH2Cl2); 1H NMR (400 MHz, CDCl3):
d 7.35–7.15
23
(m, 110H, Ar–H), 5.30–5.23 (m, 3H), 5.31 (d, 1H, J1,2¼3.2 Hz, H-1),
5.30 (d, 1H, J1,2¼4.0 Hz, H-1), 5.24 (d, 1H, J1,2¼4.0 Hz, H-1), 5.18–
5.09 (m, 7H), 4.97–4.93 (m, 1H), 4.85–4.80 (m, 6H), 4.65–4.38 (m,
25H), 4.12–4.01 (m, 24H), 3.90 (t, 1H, JH,H¼8.8 Hz), 3.75 (d, 1H,
JH,H¼9.6 Hz), 3.67–3.54 (m, 16H), 3.35 (dd, 2H, J1,2¼3.2 Hz,
[a
]
D
(m, 90H, Ar–), 5.89 (ddt, 1H, JH,H¼10.8 Hz, JH,H¼10.8 Hz,
JH.CH2¼5.6 Hz, CH]CH2), 5.35 (d, 1H, JH,H¼10.8 Hz, CH), 5.33 (d, 1H,
JH,H¼10.8 Hz, CH), 5.30–5.20 (m, 9H), 5.18 (d, 1H, J1,2¼3.6 Hz, H-1),
5.15 (d, 1H, J1,2¼2.8 Hz, H-1), 5.13 (d, 1H, J1,2¼2.8 Hz, H-1), 4.99 (d,
3H, JH,H¼10.0 Hz, CH), 4.96 (d, 3H, JH,H¼9.2 Hz, CH), 4.62 (dd, 1H,
J5,6a¼4.0 Hz, J6a,6b¼12.4 Hz, H-6a), 4.64–4.49 (m, 16H), 4.43 (dd, 3H,
J5,6a¼3.2 Hz, J6a,6b¼11.6 Hz, H-6a), 4.28–3.96 (m, 24H), 3.73 (br d,
2H, JH,H¼11.6 Hz, CH), 3.69 (br d, 2H, JH,H¼11.2 Hz, CH), 3.64 (br d,
2H, JH,H¼10.8 Hz, CH), 3.74–3.56 (m, 6H), 3.38 (dd, 2H, JH,H¼3.2,
J2,3¼9.6 Hz, H-2); 13C NMR (100 MHz, CDCl3):
d 150.7 (d,
JC,P¼6.0 Hz, Cipso phosphate), 150.6 (d, JC,P¼6.5 Hz, Cipso phosphate),
139.4, 139.3, 139.2, 138.4, 138.3, 138.2 (Cipso), 129.8, 129.7, 128.2,
127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 127.0 (CHAr), 125.3, 120.2, 120.1
(CHAr–phosphate), 98.8, 98.7, 98.6, 98.5, 98.4 (C-1), 81.0, 80.8, 80.7,
80.4, 78.9, 78.7, 78.5, 75.6, 75.4, 73.4, 73.2, 72.7, 72.6, 71.9, 71.7, 71.5,
10.0 Hz); 13C NMR (100 MHz, CDCl3):
d
150.7 (d, JC,P¼6.3 Hz, Cipso
70.5, 69.3, 68.2; 31P NMR (161.9 MHz, CDCl3):
194H199NaO38P: 3190.3275; found: 3190.1707.
d
ꢀ10.7; MS: calcd for
phosphate), 150.6 (d, JC,P¼6.7 Hz, Cipso phosphate), 139.5, 139.4,
138.5, 138.4, 138.3, 138.2, 138.1 (Cipso), 134.9 (CH]), 129.8, 129.7,
128.4,128.3,128.2,128.0,127.9,127.8,127.7,127.6,127.5,127.4,127.3,
127.2, 127.0 (CHAr), 125.4, 125.3, 120.2, 120.1 (CHAr–phosphate),
117.0 (H2C]), 98.9, 98.8, 98.7, 98.6 (C-1), 81.1, 81.0, 80.7, 80.5, 80.0,
79.7, 79.5, 79.3, 79.2, 79.1, 78.9, 78.8, 78.7, 78.5, 75.8, 75.7, 75.6, 75.5,
75.4, 73.5, 72.9, 72.8, 72.7, 72.4, 72.1, 71.6, 71.5, 70.7, 70.6, 69.2, 69.1,
C
3.8. 6A-O-Phosphate-
a-cyclodextrin (18)
Compound 16 (0.66 g, 0.24 mmol) was dissolved in 1:1 MeOH–
EtOAc (30 mL). Then, Pd(OH)2 (360 mg) and TFA (cat.) were added
and the mixture was kept stirring under hydrogen atmosphere for
68.3; 31P NMR (161.9 MHz, CDCl3):
163H169NaO33P: 2708.1181; found: 2708.0223.
d
ꢀ10.6; MS: calcd for
2
days. Filtration and removal of the solvents afforded
C

´
O. Lo´pez, M. Bols / Tetrahedron 64 (2008) 7587–7593
7592
3.11. 6A-O-(Diphenylphosphate)-hexadeca-O-benzyl-
cyclodextrin (22)
a
-
compound was dissolved in 1:1 MeOH–H2O (20 mL), and to the
solution was added PtO2 (120 mg); the corresponding mixture was
vigorously stirred under hydrogen atmosphere (15 atm) for 2 days.
The solid was filtered off and the solvent was removed in vacuo; the
residue was dissolved in water (20 mL) and washed with CH2Cl2
(2ꢂ15 mL). Removal of water furnished title compound (47 mg,
To a solution of 6A-O-allyl-6D-O-(diphenylphosphate)-hexa-
deca-O-benzyl- -cyclodextrin (21) (0.44 mg, 0.16 mmol) in 2:1 abs
a
EtOH–toluene (20 mL) was added DABCO (11 mg, 0.10 mmol) and
Wilkinson’s catalyst (77 mg, 0.083 mmol), and the corresponding
mixture was refluxed for 3 h. After cooling down to rt, the solution
was concentrated to dryness and the residue was dissolved in
EtOAc (80 mL) and washed with H2O (2ꢂ50 mL); the organic layer
was dried over MgSO4, filtered and the filtrate was concentrated to
dryness. The crude residue was dissolved in a 5:3 CH2Cl2–MeOH
mixture (16 mL) and AcCl (0.18 mL, 2.53 mmol) was added at 0 ꢁC
(pH 1–2); reaction was kept at rt for 3 h. After that it was quenched
by the addition of Et3N (0.7 mL) and the solution was concentrated
to dryness; the residue was dissolved in CH2Cl2 (80 mL) and
washed with 10% KHSO4 (50 mL) and H2O (50 mL). The organic
layer was dried over MgSO4, filtered and the filtrate was concen-
trated to dryness and purified by column chromatography (pen-
65%).
23
[
a
]
D
þ56 (c 0.5, H2O); 1H NMR (400 MHz, DMSO-d6):
d 5.01 (d,
1H, J1,2¼3.2 Hz, H-1), 5.0–4.92 (m, 5H, H-1), 4.66 (br s), 4.14–4.04,
3.90–3.72, 3.70–3.52 (4m, 50H, H2–H6, –OH); 13C NMR (100 MHz,
D2O):
d 172.2 (CO), 102.0, 101.9, 101.8, 101.6, 101.4, 101.0 (C-1), 81.7,
81.6, 81.3, 81.0, 80.0, 73.3, 73.1, 72.9, 72.2, 71.9, 71.6, 71.4, 71.1, 71.0,
70.0, 64.3, 60.4, 60.3, 59.8; 31P NMR (161.9 MHz, D2O):
calcd for C36H58Na2O34P: 1111.2342; found: 1110.3525.
d 1.4; MS:
Acknowledgements
We thank the Lundbeck Foundation for generous financial
support.
tane/1:3 EtOAc–pentane) to afford title compound (317 mg, 75%).
23
[a
]
þ40 (c 0.6, CH2Cl2); 1H NMR (400 MHz, CDCl3):
d 7.30–7.00
D
(m, 90H, Ar–H), 5.48 (d, 1H, J1,2¼4.0 Hz, H-1), 5.47 (d, 1H,
J1,2¼3.6 Hz, H-1), 5.36 (d, 1H, JH,H¼11.2 Hz, CH), 5.34 (d,
1H, JH,H¼11.2 Hz, CH), 5.20 (d, 1H, JH,H¼10.8 Hz, CH), 5.15 (d, 1H,
JH,H¼10.8 Hz, CH), 4.98–4.93 (m, 3H), 4.92–4.83 (m, 6H), 4.81 (d, 3H,
JH,H¼11.2 Hz, CH), 4.70–4.63 (m, 4H), 4.57–4.38 (m, 13H), 4.54 (dd,
1H, J5,6a¼2.8 Hz, J6a,6b¼12.0 Hz, H6a), 4.36 (d, 1H, JH,H¼12.4 Hz, CH),
4.29 (d, 1H, JH,H¼12.4 Hz, CH), 4.24–3.85 (m, 20H), 3.80–3.66 (m,
6H), 3.59–3.52 (m, 3H), 3.47–3.43 (m, 3H), 3.36 (dd, 2H, J2,3¼9.6 Hz,
H-2), 3.20 (dd, 2H, J2,3¼10.0 Hz, H-2), 2.14 (br s, 1H, OH); 13C NMR
References and notes
1. Hedges, A. R. Chem. Rev. 1998, 98, 2035–2044.
2. Ferrari, F.; Sorrenti, M.; Rossi, S.; Catenacci, L.; Sandri, G.; Bonferoni, M. C.;
Caramella, C.; Bettinetti, G. Pharm. Dev. Technol. 2008, 13, 65–73.
3. Liu, Z.; Sun, X.; Nakayama-Ratchford, N.; Dai, H. ACS Nano 2007, 1, 50–56.
4. Masar, M. S., III; Gianneschi, N. C.; Oliveri, C. G.; Stern, C. L.; Nguyen, S. T.;
Mirkin, C. A. J. Am. Chem. Soc. 2007, 129, 10149–10158.
5. Carlqvist, P.; Maseras, F. Chem. Commun. 2007, 748–750.
6. Davis, A. P.; Wareham, R. S. Angew. Chem., Int. Ed. 1999, 38, 2979–2996.
7. Shpigun, O. A.; Ananieva, I. A.; Budanova, N. Yu.; Shapovalova, E. N. Russ. Chem.
Rev. 2003, 72, 1035–1054.
8. Villalonga, R.; Cao, R.; Fragoso, A. Chem. Rev. 2007, 107, 3088–3116.
9. Engeldinger, E.; Armspach, D.; Matt, D. Chem. Rev. 2003, 103, 4147–4173.
10. Motherwell, W. B.; Bingham, M. J.; Six, Y. Tetrahedron 2001, 57, 4663–4686.
11. Breslow, R.; Dong, S. D. Chem. Rev. 1998, 98, 1997–2011.
12. Rousseau, C.; Ortega-Caballero, F.; Nordstrøm, L. U.; Christensen, B.; Petersen,
T. E.; Bols, M. Chem.dEur. J. 2005, 11, 5094–5101.
13. Helmreich, E. J. M.; Klein, H. W. Angew. Chem., Int. Ed. Engl. 1980, 19, 441–455.
14. Palm, D.; Blumenauer, G.; Klein, H. W.; Blanc-Muesser, M. Biochem. Biophys. Res.
Commun. 1983, 111, 530–536.
15. Takagi, M.; Fukui, T.; Shimomura, S. Proc. Natl. Acad. Sci. U.S.A. 1982, 79,
3716–3719.
16. Klein, H. W.; Im, M. J.; Palm, D. Eur. J. Biochem. 1986, 157, 107–114.
17. Rekharsky, M. V.; Inoue, Y. J. Am. Chem. Soc. 2002, 124, 813–826.
18. Cho, A.; Ochoa Lara, K. L.; Yatsimirsky, A. K.; Eliseev, A. V. Org. Lett. 2000, 2,
1741–1743.
(100 MHz, CDCl3):
d
150.7 (d, JC,P¼7.2 Hz, Cipso phosphate), 150.6 (d,
JC,P¼7.8 Hz, Cipso phosphate), 139.4, 139.3, 138.6, 138.5, 138.4, 138.3,
138.2 (Cipso), 129.9, 129.7, 128.5, 128.4, 128.1, 128.0, 127.9, 127.7,
127.6, 127.5, 127.1, 127.0, 126.8 (CHAr), 125.4, 125.3, 120.1 (CHAr
–
phosphate), 98.8, 98.6, 98.3, 98.2, 98.1, 97.9 (C-1), 81.4, 81.1, 80.9,
80.8, 80.3, 80.2, 79.9, 79.5, 79.4, 79.2, 79.0, 78.4, 78.2, 76.7, 76.3,
76.2, 75.9, 74.7, 73.5, 73.4, 73.2, 73.0, 72.4, 72.3, 72.0, 71.8, 70.1, 70.0,
69.5, 69.3, 69.2, 68.3, 68.2, 62.4 (C-6); 31P NMR (161.9 MHz, CDCl3):
d
ꢀ10.6; MS: calcd for C160H165NaO33P: 2668.0868; found:
2668.6484.
3.12. 6A-Carboxylic acid-6DO-phosphate-
a-cyclodextrin (24)
19. Eliseev, A. V. PCT WO 2004/050709, A2, 2004.
20. Mlynarz, P.; Rudzinska, E.; Berlicki, L.; Kafarski, P. Curr. Org. Chem. 2007, 11,
1593–1609.
A solution of 6A-O-(diphenylphosphate)-hexadeca-O-benzyl-
a-
cyclodextrin 22 (0.36 g, 0.13 mmol) and Dess–Martin periodinane
reagent (171 mg, 0.40 mmol) in CH2Cl2 (10 mL) was kept at room
temperature overnight and then quenched by addition of Et2O
(25 mL) and satd aq NaHCO3 containing 5% of Na2S2O3 (25 mL).
Then, the organic layer was separated, dried over MgSO4 and
concentrated to dryness. To a solution of the residue in 2-methyl-
but-2-ene (4 mL), tBuOH (10 mL) and THF (4 mL) was added a
solution of NaClO2 (0.32 g, 3.54 mmol) and NaH2PO4 (0.29 g,
2.42 mmol) in water (2 mL) and the corresponding mixture
was kept stirring at room temperature overnight. The reaction was
quenched by addition of 1 M HCl (50 mL) and the product was
extracted with EtOAc (3ꢂ30 mL). The organic phase was dried over
MgSO4, filtered and the filtrate was concentrated to dryness and
purified by flash chromatography (1:3 EtOAc–pentane/1:2
EtOAc–pentane containing 1% HCOOH) to give 6A-carboxylic acid-
21. Cherenok, S.; Dutasta, J.-P.; Kalchenko, V. Curr. Org. Chem. 2006, 10, 2307–2331.
22. Siegel, B.; Pinter, A.; Breslow, R. J. Am. Chem. Soc. 1977, 99, 2309–2312.
23. Tarelli, E.; Lemercinier, X.; Wheeler, S. Carbohydr. Res. 1997, 302, 27–34.
24. Inoue, H.; Kawashita, T.; Nakayama, H.; Tsuhako, M. Carbohydr. Res. 2005, 340,
1766–1772.
25. Inoue, H.; Tone, N.; Nakayama, H.; Tsuhako, M. Carbohydr. Res. 2003, 338,
2067–2074.
26. Liu, Y.; Li, L.; Li, X.-Y.; Zhang, H.-Y.; Wada, T.; Inoue, Y. J. Org. Chem. 2003, 68,
3646–3657.
27. Liu, Y.; Li, B.; Han, B.-H.; Li, Y.-M.; Chen, R. T. J. Chem. Soc., Perkin Trans. 2 1997,
1275–1278.
28. Liu, Y.; Han, B.-H.; Chen, Y.-T. J. Phys. Chem. B 2002, 106, 4678–4687.
29. Pearce, A. J.; Sinay¨, P. Angew. Chem., Int. Ed. 2000, 39, 3610–3612.
30. Wang, W.; Pearce, A. J.; Zhang, Y.; Sinay¨, P. Tetrahedron: Asymmetry 2001, 12,
517–523.
31. Guieu, S.; Sollogoub, M. J. Org. Chem. 2008, 73, 2819–2828.
32. Bistri, O.; Sinay¨, P.; Barbero, J. J.; Sollogoub, M. Chem.dEur. J. 2007, 13,
9757–9774.
33. Lecourt, T.; Herault, A.; Pearce, A. J.; Sollogoub, M.; Sinay, P. Chem.dEur. J. 2004,
10, 2960–2971.
6D-O-(diphenylphosphate)-hexadeca-O-benzyl-
a-cyclodextrin 23
34. Bjerre, J.; Nielsen, E. H.; Bols, M. Eur. J. Org. Chem. 2008, 745–752.
(190 mg, 53%, two steps).
´
´
35. Lopez Lopez, O.; Marinescu, L.; Bols, M. Tetrahedron 2007, 63, 8872–8880.
36. Bjerre, J.; Hauch Fenger, T.; Marinescu, L. G.; Bols, M. Eur. J. Org. Chem. 2007,
704–710.
Compound 23 (0.19 g, 0.17 mmol) was dissolved in 1:1 MeOH–
EtOAc (10 mL). Then, Pd(OH)2 (151 mg) and TFA (cat.) were added
and the mixture was kept stirring under hydrogen atmosphere for 2
days. Filtration and removal of the solvents afforded intermediate
37. Marinescu, L. G.; Bols, M. Angew. Chem., Int. Ed. 2006, 45, 4590–4592.
38. Ortega-Caballero, F.; Bols, M. Can. J. Chem. 2006, 84, 650–658.
39. Ortega-Caballero, F.; Bjerre, J.; Lausten, L. S.; Bols, M. J. Org. Chem. 2005, 70,
7217–7226.
6A-carboxylic acid-6D-O-(diphenylphosphate)-
a-cyclodextrin. This

´
O. Lo´pez, M. Bols / Tetrahedron 64 (2008) 7587–7593
7593
40. Ortega-Caballero, F.; Rousseau, C.; Christensen, B.; Petersen, T. E.; Bols, M. J. Am.
Chem. Soc. 2005, 127, 3238–3239.
41. Marinescu, L.; Mølbach, M.; Rousseau, C.; Bols, M. J. Am. Chem. Soc. 2005, 127,
17578–17579.
45. Freimund,S.;Baldes,L.;Huwig,A.;Giffhorn, F.Carbohydr. Res.2002, 337,1585–1587.
46. Lecourt, T.; Mallet, J.-P.; Sinay¨, P. C.R. Chim. 2003, 6, 87–90.
47. Clausen, M. H.; Jørgensen, M. R.; Thorsen, J.; Madsen, R. J. Chem. Soc., Perkin
Trans. 1 2001, 543–551.
42. Rousseau, C.; Christensen, B.; Bols, M. Eur. J. Org. Chem. 2005, 2734–2739.
43. Rousseau, C.; Christensen, B.; Petersen, T. E.; Bols, M. Org. Biomol. Chem. 2004, 2,
3446–3482.
48. McElroy, W. D.; Glass, B. Phosphorus Metabolism; Johns Hopkins University
Press: Baltimore, MD, 1951; Vol. I.
49. Remko, M.; Van Duijnen, P. T.; von der Lieth, C.-W. J. Mol. Struct. (Theochem)
2007, 814, 119–125.
44. Yu, K. L.; Fraser-Reid, B. Tetrahedron Lett. 1988, 29, 979–982.