Synthesis of cationic glyco-oligoamide for DNA-carbohydrate interaction studies

Article abstract of DOI:10.1080/10610278.2013.814776

We are using carbohydrate-based ligands, glyco-oligoamides, as a strategy to obtain structural and thermodynamic information on carbohydrate-minor groove DNA binding. In order to improve the solubility of the first generation of neutral ligands type 1 in

Full text of DOI:10.1080/10610278.2013.814776

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Supramolecular Chemistry
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Synthesis of cationic glyco-oligoamide for
DNA–carbohydrate interaction studies
Andrea Taladriz-Sendera & Cristina Vicenta
a Departamento de Síntesis, Estructura y Propiedades de los Compuestos Orgánicos (SEPCO),
Instituto de Química Orgánica General, CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain
Published online: 29 Aug 2013.
To cite this article: Andrea Taladriz-Sender & Cristina Vicent (2013) Synthesis of cationic glyco-oligoamide for
DNA–carbohydrate interaction studies, Supramolecular Chemistry, 25:9-11, 656-664, DOI: 10.1080/10610278.2013.814776
To link to this article: http://dx.doi.org/10.1080/10610278.2013.814776
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Supramolecular Chemistry, 2013
Vol. 25, Nos. 9–11, 656–664, http://dx.doi.org/10.1080/10610278.2013.814776
Synthesis of cationic glyco-oligoamide for DNA–carbohydrate interaction studies
A n d re a T a l a d r i z - Se n d e r a n d C r i s ti n a V i c e n t *
´ ´ ´ ´
Departamento de Sıntesis, Estructura y Propiedades de los Compuestos Organicos (SEPCO), Instituto de Quımica Organica General,
CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain
( Received 8 May 2013; final version received 5 June 2013)
W e a r e u s i n g c a r b o hy d r a t e - b a s e d l i g a nd s , g l y c o - ol i g o a m i d e s , a s a s t r a t e g y t o o b t a i n s t r u c t u r a l a n d t h e r m o dy n a m i c
i n f o r m a t i o n o n c a r b o hy d r a t e – m i no r g r oo v e D N A b i n d in g . I n o r d e r t o i m p r ov e t h e s o l u b il i t y o f t h e fi r s t g e n e r a t i o n o f n e u t r a l
l i g a n d s t y p e 1 in aqueous solution and the stability of the complexes formed with DNA as well as their sequence selectivity
towards AT/TA base pairs, a new cationic vector b-D-Xyl-Py-g[3(R)NHþ3 ]-Py-Ind 2 has been designed. Here, we present an
efficient convergent solution-phase synthesis of the xylose cationic glyco-oligoamide 2, evidence of improvement of water
solubility and the binding to polymers of DNA when compared with the xylose neutral ligand 1. This synthetic work paves
the way to the synthesis of glyco-oligoamides with carbohydrates which contain in their structure cooperative hydrogen
bonding centres based on our previous studies on carbohydrate cooperativity in apolar media and the use of the new design to
achieve multivalency with calixaren-based platforms.
Keywords: m ol e c ul a r r e c o g ni t i o n; c a r b o hy d r a t e i n t e r a c t i o n s; c a r b o h y dr a t e – D N A b i n d in g
Introduction
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parameters of the interaction with oligonucleotides arises.
Thus, in order to improve the solubility of these neutral
ligands in aqueous solution and the stability of the
complexes formed with DNA as well as their sequence
selectivity towards AT/TA base pairs, the new cationic
vector has been designed (Figure 1).
t
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( 1). In addition, they take part in the structure of
nuclear glycoproteins which act as a transcription factor,
and in some cases there is a correlation between
glycosylation and DNA complex formation (2, 3). The
interactions at the origin of neutral carbohydrates
recognition processes are hydrogen bonding and CH–p
interactions as proposed initially by Lemieux and Quiocho
after inspection of the crystalline structure of lectine–
carbohydrate complexes (4, 5). However, quantification in
water of their contribution to binding in different
recognition processes is at the moment a question of
current debate (6–8). We want to learn to control these
interactions in the context of DNA groove binding.
A c c o r d i n g t o s e v e r a l s t u d i e s b y D e r v a n ( 20, 21) and
Sugiyama (22, 23), selective chiral substitution on the g-
aminobutyric acid linker with a cationic group (NHþ3 )
enhances the properties of the polyamide hairpins with
regard to DNA affinity and sequence specificity. Thus, we
have selected the side-by-side pairing of pyrrole amino
acids (Py) covalently joined head-to-tail by an (R)-
3,4-diaminobutyric acid linker (6) which results in a b-
amine residue at the g-turn unit (g[3(R)NHþ3 ]). Conse-
quently, the core of the molecule keeps a design
comparable to our neutral vector analogue (Figure 1,
compound 2). Again, the carbohydrate for study was
placed at C-terminal and an indole ring (Ind) was included
at the N-terminal, with the aim to drive the conformational
equilibrium towards the folded conformation through
CH–p interactions, as already achieved in our previous
design.
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* C o rr e sp o n d i n g a u t ho r . E ma il : c v i c e n t @i q o g. c s i c . e s
q 2 0 1 3 T a y l o r & F r a n c i s

Supramolecular Chemistry
6
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chromatography. Finally, evidence of enhancement of
either solubility in water or qualitative binding affinity to
poly(dA–dT)2 of cationic ligand (2) compared with that of
the corresponding neutral analogue b-D-Xyl-Py-g-Py-Ind
(1) is shown.
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techniques intrinsically limit the scale of synthesis. Our
synthetic efforts are focused on developing an efficient
solution-phase synthesis, avoiding arduous purifications
that would allow us access to diverse families of glyco-
oligoamides.
Results and discussion
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retrosynthetic analysis shown in Scheme 1. Coupling of
the two subchains (b-Xyl-Py-g[3(R)NHCbz]NHBoc) 4
and (HOPy-Ind) 5 will result in a convergent synthesis
with fewer linear steps. The chains were built up from two
separate suitably protected strands, incorporating
g-diaminobutyric building block at the last stage. Late
introduction of this chiral fragment was crucial to avoid
premature deprotection of the amino group in the
g-fragment or a b-elimination process. The key step of
the synthesis is the final coupling of both strands.
( 9, 14). Our first synthesis (9) was planned as a convergent
approach. The key step was the coupling of the sugar
strand (Xyl-Py) with the indole moiety which contained
the gamma fragment (HO-g-Py-Ind). This pathway
allowed us to obtain a first generation of neutral glyco-
oligoamides with structural diversity in the carbohydrate
residue. Later, our interest to study multivalent sugar-
oligoamide systems brought us the opportunity to improve
the synthetic methodology. Then a new linear synthesis
allowed us to introduce a wild structural diversity in the
sugar as well as in the pyrrole B (14). The skeleton of the
oligoamide was obtained by a linear synthesis, incorporat-
ing the sugar at the last stage.
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3
couplings of Ind 8 to Py 9, followed by ester saponification
and coupling to Boc-deprotected sugar strand 4, afford
protected xylose-oligoamide 3 in a convergent manner.
Sugar moiety 7 was prepared from building blocks 10 and
11, which have been previously synthesised in our
laboratory and by others (14, 24).
T
o
s
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-
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[
3
( R)NHþ3 ]-Py-Ind (2), we need to reconsider the synthetic
strategy. Here, we present a convergent solution-phase
synthesis in which indole strand (OH-Py-Ind) was
synthesised first, next the sugar strand (b-Xyl-Py-NO2)
was synthesised and finally the g-diaminobutyric fragment
was introduced. Incorporation of g-diaminobutyric part in
the last moment was crucial to avoid premature
deprotection of the amino group or b-elimination. Here
we show that this new pathway allows getting a new family
of cationic glyco-oligoamides with the additional advan-
tage of allowing introducing structural diversity in the g-
turn unit. Furthermore, an optimised synthesis has been
T h e s y n t h e s i s o f t h e s u g a r s t r a n d 7 (b-Xyl-Py-NO2)
(Scheme 2) begins with the catalytic hydrogenation (10%
Pd/C, MeOH) of xylose azide 11 to obtain amine 12. The
xylose azide compound was synthesised from commer-
cially available xylose using a described procedure (14).
1-Methyl-4-nitropyrrole-2-carboxylic acid 10 (24) was
prepared for coupling with protected amine 12. The amido
glycosidic bond formation to afford 7 is one of the key

6
5
8
A. Taladriz-Sender and C. Vicent
Me
O
OH
Me
O
HO
HO
OAc
N
B
AcO
AcO
N
B
N
H
O
O
N
H
O
O
N
H
N
H
H
N
H
N
NH3
NHCbz
N
N
H
A
N
Me
H
O
NH
A
N
Me
O
NH
O
O
2
3
β-D-Xyl-Py- γ [3(R)NH3+]-Py-Ind
O
Me
N
O
AcO
AcO
OAc
HO
Me
N
O
OAc
O
+
N
AcO
AcO
H
N
NHCbz
O
O
H
NO2
NHBoc
6
N
H
7
NHCbz
NHBoc
4
+
Me
N
O
O
AcO
AcO
N3
H
N
HO
OH
O
+
OAc
N
H
NO2
11
O
N
Me
10
5
OMe
O
O2N
OH
N
+
N
Me
H
O
8
9
S c h e m e 1 . R e t r o s y nt h e t i c s t r a t e g y f o r t h e c o n ve r g e n t s o l u t i on - p h a s e s y n t h e s is o f X y l - P y - g[ 3 ( R)NHþ3 ]-Py-Ind 2.
steps in the synthetic strategy. The choice of coupling
reagents is always critical. In contrast to our previous
convergent approach, amide 7 was reached by the
activation of acid 10 with O-(Benzotriazol-1-yl)-N,N,N0,
N0-tetramethyluronium hexafluorophosphate (HBTU) and
Hunig’s base. A side reaction can often take place when
using this coupling reagent. The amine reacting with the
coupling agent can form a guanidinium by-product (29),
thus the order of addition and timing are relevant. However,
HBTU gave the best results affording amide 7 in 72% yield.
Furthermore, a major fraction of the b-anomer was isolated
by precipitation in EtOH with no need of chromatographic
purification. Nitro group from 7 was converted into amine
13 by catalytic hydrogenation (10% Pd/C, DCM/MeOH)
and used without further purification in the next amide bond
formation. This time, the activation of commercially
available acid 6 was carried out with (Benzotriazol-1-
yloxy)tripyrrolidinophosphonium hexafluorophosphate
(PyBOP). The advantage of phosphonium salts over the
aminium/uranium salts was to avoid the guanidinium side
reaction (30). Therefore, introduction of gamma moiety
was successfully achieved to obtain sugar fragment 4
(b-Xyl-Py-g[3(R)NHCbz]NHBoc) in 70% yield.
I
n
d
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t
e
p
s
f
r
o
m
t
h
e
e
d
u
c
e
d
m
e
t
h
y
l
-
4
-
n
i
t
r
o
p
y
r
r
o
l
e
-
2
-
c
a
r
b
o
x
-
y l a t e 9 by coupling PyBOP-activated indole-2-carboxylic
acid 8, yielding ester 15 in 90% yield. Saponification of the
ester with 10% NaOH(aq) in dioxane yielded product 5.
Remarkably, chromatographic purifications were not
required for the synthesis of this strand.
W it h b ot h s tr an ds i n h an d (4 and 5), the assembly of core
cationic xylose-oligoamide 2 was initiated (Scheme 3).
Carbamate protecting group from sugar moiety 4 was
removed with Trifluoroacetic acid (TFA) in Dichloro-
methane (DCM), yielding amine 16 in 95% yield. PyBOP-
mediated coupling of indole fragment 5 to a small excess of

Supramolecular Chemistry
6
5
9
OAc
N3
AcO
AcO
11
O
10% Pd/C
MeOH
80%
O
Me
N
O
OAc
O
Me
N
O
OAc
AcO
AcO
12
AcO
AcO
NH2
OAc
O
PyBOP, DIEA
N
HBTU, DIEA
AcO
AcO
HO
7
O
N
H
+
O
H
+
Me
N
N
DMF
70%
DMF
72%
NHCbz
O
H
R
NHBoc
6
R = NO2
NHCbz
NHBoc
H2, Pd/C
DCM/MeOH
HO
4
R = NH2 13
NO2
10
R
H
N
PyBOP, DIEA
H
N
10 % NaOH(aq)
+
OH
OMe
OMe
O
OH
N
Me
N
H
N
N
H
DMF
90%
Dioxane/H2O
90%
O
H
O
O
O
O
N
Me
N
Me
8
NaBH4, Pd/C
MeOH/AcOEt
9
R = NO2
R = NH2
15
5
14
S
c
h
e
m
e
2
.
S
y
n
t
h
e
s
i
s
o
f
s
u
g
a
r
s
t
r
a
n
d
(
b
-
X
y
l
-
P
y
-
g
[
3
(
R
)
N
H
C
b
z
]
N
H
B
o
c
)
4
a
n
d
i
n
d
o
l
e
s
t
r
a
n
d
(
O
H
-
P
y
-
I
n
d
)
5
.
amine 16 delivered the desired protected xylose-oligoamide
3 in 65% yield. Acetate cleavage of the hydroxyl group from
the sugar with sodium methoxide followed by Cbz
deprotection by hydrogenation (Pd/C, 40psi H2) for 6–8 h
affords free amine Xyl-Py-g[3(R)NH2]-Py-Ind. Subsequent
treatment with HCl 0.5 M gives the target final product 2
which was purified by reverse-phase HPLC.
a
f
fi
n
i
t
y
o
f
t
h
e
n
e
w
c
a
t
i
o
n
i
c
g
l
y
c
o
-
o
l
i
g
o
a
m
i
d
e
( 2) which was
1
compared with that of its neutral analogue (1). H NMR
titrations with both glyco-oligoamides were carried out.
Increasing amounts of poly(dA–dT)2 were added to a
constant concentration solution of cationic xylose glyco-
oligoamide (2) and neutral xylose glyco-oligoamide (1),
respectively, in phosphate buffer/D2O. Differences in the
kinetics of the free/bound exchange process could affect the
chemical shifts, line intensities and/or the line widths of the
ligand resonances. These perturbations enable monitoring
S
o
l
u
b
i
l
i
t
y
o
f
b
o
t
h
l
i
g
a
n
d
s
1
a
n
d
2
i
n
p
h
o
s
p
h
a
t
e
b
u
f
f
e
r
(pH 7.2) was analysed by UV–vis spectroscopy. Saturated
solutions of both glyco-oligoamides were prepared, let to
stabilise and filtered. Concentration of the resulting filtrate
was measured by UV–vis spectroscopy using their respective
molar extinction coefficients [1302 ¼ 24,745 M21 cm21 (1)
and 1302 ¼ 24,938 M21 cm21 (2)]. As was expected,
concentration value obtained for the cationic xylose glyco-
oligoamide (854 mM) was higher than for its neutral analogue
(478 mM).
1
of the DNA binding. In this qualitative H NMR binding
experiment (9) with polymers of DNA, we follow the line
broadening of resonances from compounds 1 and 2, which
eventually disappeared below the noise level upon addition
of DNA. Complete disappearance of the 1H-signals
indicates formation of the complex (Figure 2).
A
s
c
a
n
b
e
o
b
s
e
r
v
e
d
i
n
F
i
g
u
r
e
2
,
f
o
r
e
q
u
a
l
l
i
g
a
n
d
P
e
r
e
l
i
m
i
n
a
r
y
o
i
n
t
e
r
a
c
t
i
o
n
s
t
u
d
i
e
s
w
i
t
h
p
e
o
l
y
(
d
A
–
d
T
)
c
o
n
c
e
n
t
r
a
t
i
o
n
,
a
s
i
g
n
i
fi
c
a
n
t
d
i
f
f
e
r
e
n
c
e
(
fi
v
e
f
o
l
d
)
i
n
t
h
e
2
w
e
r
c
a
r
r
i
e
d
u
t
t
o
q
u
a
l
i
t
a
t
i
v
e
l
y
e
v
a
l
u
a
t
t
h
e
b
i
n
d
i
n
g
l
i
g
a
n
d
/
p
o
l
y
m
e
r
r
a
t
i
o
i
s
n
e
e
d
e
d
f
o
r
c
o
m
p
l
e
t
e
d
i
s
a
p
p
e
a
r
a
n
c
e
Me
N
O
OAc
N
AcO
AcO
O
O
H
N
H
NHCbz
4
NHBoc
TFA
DCM
80%
Me
N
O
Me
N
O
OH
OAc
HO
HO
AcO
AcO
-NH2
16
O
N
O
1) NaOEt, MeOH
r.t, 70%
O
O
H
PyBOP, DIEA
0˚
N
H
N
H
H
N
H
N
DMF
65%
2)i) H2, Pd/C, DMF
6h, r.t.
NH3
NHCbz
N
N
H
O
NH
H
ii) 0.5 M HCl
O
NH
N
Me
N
Me
80%
H
N
O
OH
O
N
H
2
3
O
O
N
Me
5
þ
S
c
h
e
m
e
3
.
F
i
n
a
l
c
o
u
p
l
i
n
g
a
n
d
g
l
o
b
a
l
d
e
p
r
o
t
e
c
t
i
o
n
f
o
r
t
h
e
s
y
n
t
h
e
s
i
s
o
f
X
y
l
-
P
y
-
g
[
3
(
R
)
N
H
]
-
P
y
-
I
n
d
(
2
)
.
3

6
6
0
A. Taladriz-Sender and C. Vicent
1
F i g u r e 2 . H N MR s p e c t r a o f t h e a r o ma ti c r e g i on o f n e u t r a l x y l o s e g l y c o - ol i g o a m i d e 1 and cationic xylose glyco-oligoamide 2 at
different ratios ligand/poly(dA–dT)2 in phosphate buffer/D2O.
o
n
f
t
h
e
s
i
g
n
a
l
s
f
r
o
m
c
a
t
i
o
n
i
c
v
e
c
t
o
r
c
o
m
p
a
r
e
d
w
i
t
h
t
h
e
Experimental
e
u
t
r
a
l
v
e
c
t
o
r
,
s
u
g
g
e
s
t
i
n
g
a
n
i
m
p
r
o
v
e
m
e
n
t
i
n
t
h
e
b
i
n
d
i
n
g
C
h
e
m
i
c
a
l
s
w
e
r
e
p
u
r
c
h
a
s
e
d
f
r
o
m
S
i
g
m
a
-
A
l
d
r
i
c
h
(
S
c
h
n
e
l
l
-
a
f
fi
n
i
t
y
.
d
o
r
f
/
G
e
r
m
a
n
y
)
a
n
d
w
e
r
e
u
s
e
d
w
i
t
h
o
u
t
f
u
r
t
h
e
r
p
u
r
i
fi
c
a
t
i
o
n
.
( R)-3,4-Cbz-Dbu(Boc)-OH was purchased from Sigma-
Aldrich CAS 108919-51-3 (code number 17974). Poly
(dA–dT)2, 25 mm, was purchased from Sigma-Aldrich
(code number PO883) and used without further purifi-
cation. Solvents were purified according to the standard
procedures. Flash column chromatography was carried out
Conclusions
I
n
c
o
n
c
l
u
s
i
o
n
,
a
n
e
f
fi
c
i
e
n
t
c
o
n
v
e
r
g
e
n
t
s
o
l
u
t
i
o
n
-
p
h
a
s
e
s
y
n
t
h
e
t
i
c
r
o
u
t
e
t
o
c
a
t
i
o
n
i
c
g
l
y
c
o
-
o
l
i
g
o
a
m
i
d
e
s
h
a e
e 2 was
s
b
e
n
d
e
s
c
r
i
b
e
d
.
T
h
e
x
y
l
o
s
e
c
a
t
i
o
n
i
c
g
l
y
c
o
-
o
l
i
g
o
a
m
i
d
˚
by using silica gel (60 A pore size, 40–63 mm, Merck,
synthesised, and the solubility and preliminary binding
studies to polymers of DNA suggested that either the
solubility in aqueous solution or the binding to poly(dA–
dT)2 has been improved when compared with the neutral
ligand 1. This synthetic work paves the way to the
synthesis of glyco-oligoamides with carbohydrates which
contain in their structure cooperative hydrogen bonding
centres based on our previous studies on carbohydrate
cooperativity in apolar media (31–35), and the use of the
new design to achieve multivalency with calixaren-based
platforms (36–38) has already been successfully used
for cell penetration and DNA delivery by the Parma
group (39).
Darmstadt, Hesse, Germany). The reactions were mon-
itored by thin layer chromatography on silica gel-coated
plates (Merck 60 F254). NMR measurements were recorded
on a Varian Inova-300 (300 MHz), Varian Inova-400
(400MHz), Mercury-400 (400MHz), Varian Unity-500
(500MHz) and Bruker AVANCE 500 MHz spectrometers
which were calibrated by using the residual undeuterated
solvent as an internal reference. The abbreviations used to
explain multiplicities are s, singlet; d, doublet; t, triplet; appt,
apparent triplet; q, quartet; m, multiplet; br., broad. Mass
spectrometry analyses were carried out with an HP series
1100 MSD by electrospray ionisation (ESI). High-resolution

Supramolecular Chemistry
6 61
mass spectra (HR-MS) were recorded with an Agilent 6520-
Accurate-Mass LC/MS Q-TOF mass spectrometer. IR
experiments were recorded with a PerkinElmer Spectrum
One FT-IR spectrometer (Shelton, CT, USA). Optical
rotations were measured on a PerkinElmer 241MC
polarimeter (Shelton, CT, USA) in a 1-dm cell. Elemental
analyses were measured on a Carla Erba CHNS-O EA1108
chromatography system. Semi-preparative HPLC–MS was
run with a SunFire Prep. C18, (50 mm £ 4.6 mm £ 5 mm)
column on a Waters separation module (Waters 2545/SFO/
2767) coupled to a Waters 3100 mass detector using ESIþ.
The fractions were collected with a Waters 2767 sampler
manager. The following HPLC conditions were used: H2O:
CH3CN (98:2 ! 5:95), HCO2H (0.1%), flow rate of 1 ml/
min and UV detection using diode array
(l ¼ 190 2 400 nm). The UV absorption spectra of the
samples were recorded using a double-beam PerkinElmer
Lambda 35 UV–vis spectrophotometer, with standard 10-
mm path length cuvettes. The interval of measured
wavelengths is between 200 and 600 nm. For all the cases,
the scanning speed was fixed at 240 nm min21 and the width
ofthe slitsat2 nm. The0.2 mm nylonfilterswereprovidedby
Symta (Madrid, Spain). Water was purified using a Milli-Q
system. Melting pointsof solid compounds 2–5, 7 and 15are
not reported because decomposition was observed below the
melting temperature.
(CONH), 169.2 (COCH3), 169.7 (COCH3), 170.1
(COCH3). MS (ESþ) m/z: 450.0 [M þ Na]þ, 428.0
[M þ H]þ. Elemental analysis calcd (%) for C17H21O10N3
(427.36): C, 47.78; H, 4.95; N, 9.83. Found: C, 48.00; H,
5.02; N, 10.08. HR-MS-ESI: m/z ¼ 427.1227, calcd for
C17H21O10N3 [M þ H]þ: 427.1223. IR (KBr) n (cm21):
3375, 1739, 1531,1313, 1224, 1067 and 1036.
b-(OAc)3Xyl-Py-g[3(R)NHCbz]NHBoc (4)
( Ac O) - Xy l- Py -N O (7) (375.0mg, 0.90mmol) dissolved in
3 2
MeOH (5ml) and DCM (5ml) was treated with 10% Pd/C
(68.5 mg, 20 mol%) and hydrogenated overnight. The
mixture was filtered over a pad of Celite, and the solvent
was removed under reduced pressure to afford amine (AcO)
3-Xyl-Py-NH2 (13) which was used without further
purification. In the meantime, a solution of (R)-3,4-Cbz-
Dbu(Boc)-OH (6) (275.0 mg, 0.78 mmol) and PyBOP
(447.5mg, 0.86mmol) in DMF (2 ml) and DIEA (367ml,
2.11mmol) was stirred at rt for 40min. This solution was
then added to amine 13 and stirred overnight at rt.
Evaporation of the solvent and purification by column
chromatography (Hex:EtOAc, gradient 1:2 to 1:10) afforded
the title compound as yellowish solid (392mg, 70%).
20
Rf ¼ 0.37(Hex:EtOAc, 1:3, v/v). ½aꢀD ¼ 27.2 (c ¼ 0.95in
DMSO). 1H NMR (400MHz, DMSO-d6): d 1.36 (s, 9H, t-
Bu), 1.90 (s, 3H, CH3), 1.97 (s, 3H, CH3), 2.00 (s, 3H, CH3),
2.35–2.41(m, 2H, CH2 gc), 3.03(t, J ¼ 5.9 Hz, 2H, CH2 ga),
3.56(appt, J ¼ 10.9Hz, 1H, H5 ax),3.77(s, 3H, NCH3), 3.90
(dd, J ¼ 10.9Hz, 5.6, 1H, H5 ec), 3.93–3.97(m, 1H, CH gb),
4.80 (ddd, J ¼ 10.1, 10.1, 5.5Hz, 1H, H4), 4.98 (d,
J ¼ 3.3 Hz, 2H, CH2 Cbz), 5.06 (appt, J ¼ 9.3 Hz, 1H,
H2), 5.30 (appt, J ¼ 9.5 Hz, 1H, H3), 5.33 (appt, J ¼ 9.3 Hz,
1H, H1), 6.73 (d, J ¼ 1.6 Hz, 1H, CH Py-3B), 6.81 (t,
J ¼ 5.9 Hz, 1H, NHBoc), 7.06 (d, J ¼ 8.4 Hz, 1H, NHCbz),
7.19 (d, J ¼ 1.6 Hz, 1H, CH Py-5B), 7.29–7.36 (m, 5H,
(AcO)3-b-Xyl-Py-NO2 (7)
2
,
3
,
4
-
T
r
i
-
O
-
a
c
e
t
y
l
-
b
-
D
-
x
y
l
o
p
y
r
a
n
o
s
y
l
a
m
i
n
e
(
1
2
)
o
b
t
a
i
n
e
d
in 80% yield by hydrogenation (10% Pd/C, MeOH) (14) of
the corresponding azide 11 (1.00 g, 3.32 mmol) was added
to a mixture of HO-Py-NO2 (10) (565 mg, 3.32 mmol),
HBTU (1.38 g, 3.65 mmol) and DIEA (1.16 ml,
6.64 mmol) dissolved in DMF (2.0 ml) previously stirred
at room temperature (rt) for 30 min. After 16 h, a white
precipitate was formed in the reaction mixture. The
precipitate was isolated by vacuum filtration, and cold
ethanol was added to the residual filtrate yielding a white
precipitate. Both precipitates were crystallised in pure
ethanol to provide (AcO)3-Xyl-Py-NO2 in 72% yield, as a
white crystalline solid containing just a pure b-anomer (9).
Rf ¼ 0.39 (CH2Cl2:EtOAc, 8:2, v/v). [a ]2D0 ¼ 253.9
Cbz), 8.60 (d, J ¼ 9.4 Hz, 1H, NH5), 9.82 (s, 1H, NH4). 13
C
NMR (101 MHz, DMSO) d 20.4 (CH3), 20.5 (CH3), 20.5
(CH3), 28.2 (t-Bu), 36.1 (CH3), 38.3 (CH ga), 43.4 (CH gc)
48.7 (CH gb), 63.3 (CH5), 65.1 (CH2Cbz), 68.7 (CH4), 70.6
(CH2), 72.8 (CH3), 77.7 (CH1), 77.8 (C t-Bu), 104.8 (CH Py-
3B), 119.0 (CH Py-5B), 121.6 (C Py), 122.1 (C Py), 127.6
(CH ar), 127.7 (CH ar), 128.3 (CH ar), 137.1 (Cbz), 155.5
(CO Cbz), 155.8 (CO BOC), 161.0 (CONH), 167.0 (CONH),
169.1 (COCH3), 169.6 (COCH3) and 169.7 (COCH3). MS
(ES þ ) m/z: 754.3 [M þ Na]þ, 732.3 [M þ H]þ. HR-MS-
ESI: m/z ¼ 731.3034, calcd for C34H45O13N5 [M þ H]þ,
731.3034. IR (KBr) n (cm21): 3418, 1754, 1714, 1521, 1231
and 852.
1
(c ¼ 1 in chloroform). H NMR (400 MHz, DMSO): d
1.93 (s, 3H, CH3), 1.98 (s, 3H, CH3), 2.00 (s, 3H, CH3),
3.61 (appt, J ¼ 10.9 Hz, 1H, H5 ax), 3.89 (s, 3H, CH3),
3.91 (dd, J ¼ 5.5 Hz, 11.2 Hz, 1H, H5 ec), 4.82 (ddd,
J ¼ 10.5 Hz, 9.6, 5.5 Hz, 1H, H4), 5.01 (appt, J ¼ 9.3 Hz,
1H, H2), 5.31 (appt, J ¼ 9.6 Hz, 1H, H3), 5.35 (appt,
J ¼ 9.2 Hz, 1H, H1), 7.49 (d, J ¼ 2.0 Hz, 1H, CH Py-3B),
8.19 (d, J ¼ 2.0 Hz, 1H, CH Py-5B), 9.07 (d, J ¼ 9.3 Hz,
1H, NH 5). 13C NMR (101 MHz, DMSO) d 20.4 (CH3),
20.5 (CH3), 20.5 (CH3), 37.5 (NCH3), 63.3 (CH5), 68.6
(CH4), 70.6 (CH2), 72.7 (CH3), 77.7 (CH1), 108.8 (CH Py-
3B), 125.1 (C Py), 128.8 (CH Py-5B), 133.8 (CNO2), 160.0
MeO-Py-Ind (15)
A
w
m
i
x
t
u
r
e
o
f
N
a
B
H
(
9
o
2
m
g
,
2
.
4
4
m
m
o
l
)
i
n
w
a
t
e
r
(
2
m
l
)
(9)
4
a
s
a
d
d
e
d
d
r
o
p
w
i
s
e
t
a
s
o
l
u
t
i
o
n
o
f
M
e
O
-
P
y
-
N
O
2
(150 mg, 0.82 mmol) and Pd/C (10%) (30 mg) in EtOAc:

6
6
2
A. Taladriz-Sender and C. Vicent
MeOH (3:3) at 08C. The reaction mixture was allowed to
warm up to rt and was stirred for 30 min. The catalyst was
removed by vacuum filtration through Celite, and the
solvent was evaporated to afford amine (14), which was
used without further purification. A solution of 2-indole
carboxylic acid (8) (120 mg, 0.75 mmol), PyBOP
(429 mg, 0.83 mmol) and DIEA (261 ml, 1.5 mmol) in
DCM (2 ml) was stirred at rt for 30 min. Next, a solution
of amine (14) in DCM (2 ml) was added to the previous
activated acid and was stirred at rt overnight. The reaction
mixture was washed with HCl (1 M), extracted with
DCM, washed with brine, dried over Na2SO4, then
filtered and the solvent was evaporated in vacuo. A white
solid was obtained in 90% yield. Rf ¼ 0.57 (Hex:EtOAc,
[M þ Na]þ. Elemental analysis calcd (%) for C15H13O3N3
(283.09): C, 63.60; H, 4.63; N, 14.83. Found: C, 63.31; H,
4.80; N, 14.62. HR-MS-ESI: m/z ¼ 283.0957 calcd for
C15H13O3N3 [M þ H]þ, 283.0966. IR (KBr) n (cm21):
3437, 1653, 1558, 1457 and 748.
b-(OAc)3Xyl-Py-g[3(R)NHCbz]-Py-Ind (3)
C o m p o u n d b- ( O A c ) X y l - P y - g[ 3 ( R)NHCbz]NHBoc (4)
3
(151 mg, 0.21 mmol) was dissolved in TFA:DCM (1:5)
and stirred for 1 h and 30 min at rt. The mixture was diluted
with DCM, evaporated and washed with sodium
bicarbonate solution, the organic layer was separated,
dried over MgSO4, filtered and evaporated under vacuum
to yield compound (15) b-(OAc)3Xyl-Py-g[3(R)NHCbz]
NH2 (126 mg, 95%). Amine (16) was pure enough to be
used without further purification.
1
1:1, v/v). H NMR (400 MHz, DMSO-d6): d 3.76 (s, 3H,
OCH3), 3.88 (s, 3H, NCH3), 6.97 (d, J ¼ 1.9 Hz, 1H, CH
Py-3A), 7.05 (ddd, J ¼ 8.0 Hz, 7.0, 1.0, 1H, CH Ind-6),
7.20 (ddd, J ¼ 8.0 Hz, 7.0, 1.0, 1H, CH Ind-5), 7.27 (dd,
J ¼ 2.2 Hz, 1.0, 1H, CH Ind-3), 7.46 (dd, J ¼ 8.0 Hz, 1.0,
1H, CH Ind-7), 7.51 (d, J ¼ 1.9 Hz, 1H, CH Py-5A), 7.65
(d, J ¼ 8.0 Hz, 1H, CH Ind-4), 10.35 (s, 1H, NH2), 11.68
(s, 1H, NH1). 13C NMR (101 MHz, DMSO) d 36.3
(NCH3), 51.1 (OCH3), 102.9 (CH Ind-3), 108.4 (CH Py-
3A), 112.4 (CH Ind-4), 118.9 (C Py), 119.9 (CH Ind-6),
120.9 (CH Py-5A), 121.6 (CH Ind-7), 122.6 (C Ind),
123.5 (CH Ind-5), 127.1 (C Py), 131.5 (C Ind), 136.7 (C
Ind), 158.3 (CONH) and 160.8 (COCH3). MS (ES 2 ) m/
z: 296.0 [M 2 H]2. Elemental analysis calcd (%) for
C16H15O3N3 (297.31): C, 64.64; H, 5.09; N, 14.13.
Found: C, 64.51; H, 5.02; N, 14.22. HR-MS-ESI: m/
z ¼ 297.1113, calcd for C16H15O3N3 [M þ H]þ,
297.1118. IR (KBr) n (cm21): 3359, 3271, 1681, 1644,
1566, 1451 and 1250.
A
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8
m
m
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)
,
PyBOP (103 mg, 0.20 mmol) and DIEA (85 mM,
0.49 mmol) in 2 ml of DMF was stirred at rt. for 1 h.
Then, a solution of amine 16 (120 mg, 0.19 mmol) in DMF,
1 ml, was added to the reaction mixture and stirred
overnight. Next, the solvent was evaporated and the
product was purified by column chromatography (toluene:
MeOH, 10:1), yielding a yellow solid (105 mg, 65%).
20
Rf ¼ 0.16 (toluene:MeOH, 5:1, v/v). ½aꢀD ¼ 22.8
1
(c ¼ 0.93 in DMSO). H NMR (500 MHz, DMSO-d6):
1.90 (s, 3H, CH3), 1.97 (s, 3H, CH3), 2.00 (s, 3H, CH3),
2.44–2.47 (m, 2H, CH2 gc), 3.33–3.36 (m, 2H, CH2 ga),
3.56 (appt, J ¼ 10.9 Hz, 1H, CH, H5 ax), 3.77 (s, 3H,
CH3), 3.82 (s, 3H, CH3), 3.90 (dd, J ¼ 10.9 Hz, 5.6, 1H,
CH, H5 ec), 4.08–4.12 (m, 1H, CH gc), 4.81 (ddd,
J ¼ 10.1 Hz, 10.1, 5.6, 1H, CH, H4), 5.01 (d, J ¼ 6.8 Hz,
2H, CH2 Cbz), 5.06 (appt, J ¼ 9.3 Hz, 1H, CH, H2), 5.25–
5.37 (m, 2H, 2CH, H3, H1), 6.74 (d, J ¼ 1.9 Hz, 1H, CH
Py-3B), 6.90 (d, J ¼ 1.9 Hz, 1H, CH Py-3A), 7.05 (t,
J ¼ 7.4 Hz, 1H, CH Ind-5), 7.16–7.22 (m, 3H, 2CH Ind-6,
CH Py-5B, NHCbz), 7.25–7.33 (m, 7H, CH Cbz, CH Py-
5A, CH Ind-3), 7.46 (d, J ¼ 8.2 Hz, 1H, CH Ind-7), 7.65 (d,
J ¼ 8.0 Hz, 1H, CH Ind-4), 8.06 (t, J ¼ 6.1 Hz, 1H, NH3),
8.59 (d, J ¼ 9.5 Hz, 1H, NH5), 9.85 (s, 1H, NH4), 10.30 (s,
1H, NH2), 11.60 (s, 1H, NH1). 13C NMR (126 MHz,
DMSO) d 20.8 (CH3), 20.9 (CH3), 21.0 (CH3), 36.5
(NCH3), 36.6 (NCH3), 42.6 (CH ga), 49.1 (CH gc), 56.3
(CH gb), 63.7 (CH5), 65.6 (CH2 Cbz), 69.1 (CH4), 71.0
(CH2), 73.2 (CH3), 78.2 (CH1), 103.2 (CH Ind-3), 104. 7
(CH Py-3A), 105.2 (CH Py-3B), 112.7 (CH Ind-7), 118.7
(CH Py-5A), 119.5 (CH Py-5B), 120.22 (CH Ind-5), 122.0
(CH Ind-4), 122.0 (C Py), 122.1 (C Py), 122.5 (C Py),
123.5 (CH Ind-6), 123.8 (C Ind), 127.6 (C Ind), 128.1
(Cbz), 128.1 (Cbz), 128.7 (Cbz), 132.1 (C Py), 137.0 (C
Ind), 137.5 (Cbz), 156.1 (CONH Cbz), 158.6 (CONH),
161. 5 (CONH), 161.9 (CONH), 167.5 (CONH), 169.6
(COCH3), 170.0 (COCH3), 170.1 (COCH3) MS (ES þ )
m/z: 919.3 [M þ Na]þ, 897.3 [M þ H]þ. HR-MS-ESI: m/
HO-Py-Ind (5)
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1 N N a OH ( 1 3 m l ) w a s a d d e d t o a
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n
dioxane (13 ml). The reaction mixture was stirred for 3 h at
rt. The solution was then cooled to 08C and pH was
adjusted to 4–5 with an aqueous solution of 1 M HCl. The
precipitate was filtered yielding a white powder and dried
in vacuo (170 mg, 90% yield). Rf ¼ 0.19 (DCM:MeOH,
1
9:1, v/v). H NMR (400 MHz, DMSO-d6): d 3.86 (s, 3H,
NCH3), 6.91 (d, J ¼ 1.9 Hz, 1H, CH Py-3A), 7.05 (t,
J ¼ 7.5 Hz, 1H, CH Ind-6), 7.19 (t, J ¼ 7.7 Hz, 1H, CH
Ind-5), 7.26 (d, J ¼ 1.9 Hz, 1H, CH Ind-3), 7.43–7.48 (m,
2H, CH Ind-7, CH Py-5A), 7.65 (d, J ¼ 8.0 Hz, 1H, CH
Ind-4), 10.33 (s, 1H, NH2), 11.67 (d, J ¼ 2.3 Hz, 1H, NH1)
and 12.26 (s, 1H, OH). 13C NMR (101 MHz, DMSO) d
36.3 (NCH3), 102.8 (CH–3 Ind), 108.3 (CH Py-3A), 112.3
(CH Ind-4), 119.8 (CH Ind-6), 120.3 (CH Py-5A), 121.6
(CH Ind-7), 122.2 (C Py), 123.4 (CH Ind-5), 127.1 (C Ind),
131.5 (C Ind), 136.6 (C Ind), 158.2 (CONH), 162.0
(COCH3). MS (ES þ ) m/z: 284.0 [M þ H]þ, 306.0

Supramolecular Chemistry
6
6
3
z ¼ 896.3345 calcd for C44H48O13N8 [M þ H]þ,
1H, H5 ax), 3.16 (t, J ¼ 8.7 Hz, 1H, H3), 3.30–3.33 (m,
2H, H4, H2), 3.47 (ddd, J ¼ 20.0 Hz, 13.9, 7.7, 2H, CH ga),
3.66 (m, 1H, H5 ec, CH gb), 3.79 (s, 3H, CH3), 3.86 (s, 3H,
CH3), 4.78 (appt, J ¼ 8.9 Hz, 1H, H1), 4.80–5.14 (m, 3H,
OH), 6.83 (d, J ¼ 2.1, 1H, CH Py-P3B), 7.01 (d, J ¼ 2 Hz,
1H, CH Py-3A), 7.05 (appt, J ¼ 7.5 Hz, 1H, CH Ind-5),
7.18–7.22 (m, 2H, CH Ind-6, CH Py-5B), 7.29 (dd,
J ¼ 2.1 Hz, 0.7, 1H, CH Ind-3), 7.31 (d, J ¼ 1.9 Hz, 1H,
CH Py-5A), 7.46 (d, J ¼ 8.2 Hz, 1H, CH Ind-7), 7.65 (d,
J ¼ 8.1 Hz, 1H, CH Ind-4), 7.96 (d, J ¼ 5.5 Hz, 3H, NH3),
8.30 (t, J ¼ 5.9 Hz, 1H, NH3), 8.37 (d, J ¼ 8.8 Hz, 1H,
NH5), 10.17 (s, 1H, NH4), 10.35 (s, 1H, NH2), 11.62 (d,
J ¼ 2.3 Hz, 1H, NH1). 13C NMR (126 MHz, DMSO) d
36.2 (NCH3), 36.3 (NCH3), 35.1 (CH2 gc), 40.0 (CH2 ga),
48.4 (CH gb), 67.4 (CH5), 69.7 (CH4), 71.6 (CH2), 77.7
(CH3), 80.5 (CH1), 102.9 (CH Ind-3), 104.4 (CH Py-3A),
104.8 (CH Py-3B), 112.3 (CH Ind-7), 118.7 (CH Py-5A),
119.8 (CH Py-5B), 121.4 (CH Ind-5), 121.5 (CH Ind-4),
121.9 (C Py), 122.4 (C Py), 122.5 (C Py), 123.4 (CH Ind-
6), 127.1 (C Ind), 131.6 (C Py), 136.6 (C Ind), 158.3
(CONH), 161.2 (CONH), 162.0 (CONH), 166.1 (CONH).
MS (ES þ ) m/z: 638.3 [M þ H]þ.
896.3317.
b-Xyl-Py-g[3(R)NH2]-Py-Ind (2)
A s o l u ti o n o f b- ( O A c ) X y l - P y - g[ 3 ( R)NHCbz]-Py-Ind (3)
3
(80 mg, 0.09 mmol) in MeOH (8 ml) was treated with a
solution of sodium (67 mg, 1.25 mmol) in MeOH (8 ml) to
produce an immediate deeper yellow colour, indicative of
completion of the reaction. The solution was acidified to
pH 6 with Amberlite IR-120 ion-exchange resin (strongly
acidic), and the resin was removed by filtration.
Evaporation of the solvent under reduced pressure
afforded the title compound as an off-white solid (48 mg,
70%).
S
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P y - g[ 3 ( R)NHCbz]-Py-Ind (60 mg, 0.078 mmol) and Pd/C
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d b
-
X
y
l
-
(10% dry, 30 mg) in DMF (3 ml) was stirred at room
temperature for 8 h under H2 atmosphere at 40 psi. When
the reaction was complete, the catalyst was removed by
filtration, washed with DMF and MeOH and the solvent
evaporated in vacuo, providing the free amine as a yellow
solid. ½aꢀD ¼ 22.09. 1H NMR (500 MHz, DMSO-d6):
2.19 (dd, J ¼ 14.6, 8.3 Hz, 1H, CH gc), 2.32–2.34 (m, 1H,
CH gc), 3.05 (appt, J ¼ 10.8 Hz, 1H, H5 ax), 3.13–3.17
(m, 2H, CH ga, H3), 3.20–3.30 (m, 4H, CH ga, CH gb, H4,
H2), 3.66 (dd, J ¼ 10.8 Hz, 5.3, 1H, H5 ec), 3.78 (s, 3H,
CH3), 3.84 (s, 3H, CH3), 4.77 (appt, J ¼ 8.9 Hz, 1H, H1),
4.84 (d, J ¼ 5.7 Hz, 1H, OH), 4.93 (d, J ¼ 5.7 Hz, 1H,
OH), 5.01 (d, J ¼ 5.7 Hz, 1H, OH), 6.84 (d, J ¼ 1.8 Hz,
1H, CH Py-P3B), 6.92 (d, J ¼ 1.9 Hz, 1H, CH Py-3A), 7.05
(ddd, J ¼ 7.9 Hz, 7.0, 1.0, 1H, CH Ind-5), 7.17–7.21 (m,
2H, CH Ind-6, CH Py-5B), 7.28 (dd, J ¼ 2.1 Hz, 0.7, 1H,
CH Ind-3), 7.29 (d, J ¼ 1.8 Hz, 1H, CH Py-5A), 7.46 (dd,
J ¼ 8.2 Hz, 0.9, 1H, CH Ind-7), 7.65 (dd, J ¼ 8.1 Hz, 0.9,
1H, CH Ind-4), 8.06 (t, J ¼ 5.5 Hz, 1H, NH3), 8.32 (d,
J ¼ 8.7 Hz, 1H, NH5), 10.03 (s, 1H, NH4), 10.29 (s, 1H,
NH2), 11.61 (d, J ¼ 1.5 Hz, 1H, NH1). 13C NMR
(126 MHz, DMSO) d 36.5 (NCH3), 36.6 (NCH3), 42.0
(CH2 gc), 45.7 (CH2 ga) 49.3 (CH gb), 67.8 (CH5), 70.2
(CH4), 72.1 (CH2), 78.2 (CH3), 81.0 (CH1), 103.3 (CH
Ind-3), 104.7 (CH Py-3A), 105.0 (CH Py-3B), 112.7 (CH
Ind-7), 118.6 (CH Py-5A), 119.0 (CH Py-5B), 120.2 (CH
Ind-5), 122.0 (CH Ind-4), 122.1 (C Py), 122.3 (C Py),
122.6 (C Py), 123.6 (CH Ind-6), 123.8 (C Ind), 127.6 (C
Ind), 132.09 (C Py), 137.02 (C Ind), 158.6 (CONH), 161.8
(CONH), 161.8 (CONH), 168.8 (CONH). MS (ES þ ) m/
z: 637.3 [M þ H]þ. HR-MS-ESI: m/z ¼ 636.2656 calcd
for C30H36O8N8 [M þ H]þ, 636.2657.
Interaction NMR studies with poly(dA–dT)2
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d e s 1 and 2 to poly(dA–dT) was investigated by H
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-
1
m
NMR titration experiments. Ligand samples were prepared
at a constant concentration of 175 mM for cationic xylose-
oligoamide 2 and 130 mM neutral xylose-oligoamide 1.
Poly(dA–dT)2 stock solution was prepared by dissolving
25 unites of the oligonucleotide in 1 ml of a solution
phosphate buffer/D2O with TSP 20 mM. Under these
conditions, the concentration of poly(dA–dT) was
calculated by UV–vis spectroscopy using 1258 ¼ 13
200 M21 cm21 (c ¼ 3.02 mM bp) (40). Poly(dA–dT)2
titrant samples were prepared by diluting 250 ml of poly
(dA–dT)2 stock solution with 250 ml of ligand solution
(350 mM for cationic xylose-oligoamide 2 and 260 mM
neutral xylose-oligoamide 1). Then, 0.5 ml of the ligand
solution was introduced into the NMR tube, and increasing
amounts of the titrant DNA solution were added while
keeping the ligand concentration constant. 1H NMR
spectrum was recorded in the same conditions after each
addition of poly(dA–dT)2 (500 MHz, 64 scans, d1 ¼ 5 s,
258C).
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Solubility assay in aqueous media
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HPLC and lyophilised to dryness (32 mg, 80%). 1H NMR
(500 MHz, DMSO-d6): 2.60 (dd, J ¼ 16.7 Hz, 7.8, 1H, CH
gc), 2.67–2.76 (m, 1H, CH gc), 3.05 (appt, J ¼ 10.8 Hz,
S
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6
6
4
A. Taladriz-Sender and C. Vicent
( 1 7 ) B r e s l a u e r , J . G . ; R e m e t a , D . P . ; C h o u , W . - Y . ; F er r a n t e , R . ;
C u r r y , J . ; Z a u n c z k ow s k i , D . ; S n y de r, J . G . ; L u i s , A . ; M a r k y ,
L . A . Proc. Natl. Acad. Sci. USA 1987, 84, 8922–8926.
( 1 8 ) T r a u g e r , J . W . ; B r a i d , E . E . ; D e r v a n , P . B . Nature 1996, 382,
559–561.
( 1 9 ) W h i t e , S . ; S z e w c z y k , J . W . ; T u r n e r , J . M . ; B a ir d , E . E . ;
D e r v a n , P . B . Nature 1998, 39, 468–471.
( 2 0 ) D o s e , C . ; F a r k a s , M . E . ; C h e n o we t h , D . M . ; D er v a n , P . B .
J. Am. Chem. Soc. 2008, 130, 6859–6866.
( 2 1 ) F a r k a s , M . E . ; L i , B . C . ; D o s e , C . ; D e r v a n , P . B . Bioorg. Med.
Chem. Lett. 2009, 19, 3919–3923.
a
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t
,
1302 ¼ 24,745M21 cm21 for neutral xylose glyco-oligoa-
mide (1) and 1302 ¼ 24,938M21 cm21 cationic xylose (2)
glyco-oligoamide. Molar extinction coefficients for com-
pounds 1 and 2 were calculated in the phosphate buffer
solution according to the Lambert–Beer law.
Supporting Information Available
1
H
( 2 2 ) Z h a n g , W . ; B a n d o , T . ; S u g i ya ma , H . J. Am. Chem. Soc.
2006, 128, 8766–8776.
N
M
R
s
p
e
c
t
r
a
f
o
r
s
y
n
t
h
e
s
i
z
e
d
c
o
m
p
o
u
n
d
s
.
( 2 3 ) Z h a n g , W . ; M i n o sh i m a , M . ; S u g i ya ma , H . J. Am. Chem.
Soc. 2006, 128, 14905–14912.
( 2 4 ) B a i r d , E . E . ; D e r v a n , P . B . J. Am. Chem. Soc. 1996, 118,
6141–6146.
( 2 5 ) W u r t z , N . R . ; T u r n e r , J . M . ; B a i r d , E . E . ; D e r v a n , P . B . Org.
Lett. 2001, 3, 1201–1203.
( 2 6 ) S u , W . ; G r a y , S . J . ; D o n d i, R . ; B u r l e y , G . A . Org. Lett. 2009,
11, 3910–3913.
Acknowledgements
T h e a u t h o r s t h a n k t h e S pa ni s h M i ni s t r y o f E c o n o m y a n d
C o m p e t i t iv i t y ( P r o j e c t N o s C T Q 20 0 9- 1 0 5 47 a n d C T Q 2 0 1 2
3 2 0 2 5 ) a n d t h e E U ( C O ST - C M 1 10 2 ) f o r fi na nc i a l s u p p o r t . A . T .
-
i s g r a te fu l t o t h e M I NE C O f o r F PI p r e - do c t o r a l f e l l o ws h i p ( B E S
2 0 1 0 - 0 3 4 8 7 7 ) .
-
( 2 7 ) X i a o , J . ; Y u a n , G . ; H u a n g , W . ; C h a n , A . S . C . ; L e e , K . - L . D .
J. Org. Chem. 2000, 65, 5506–5513.
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