Self-assembly of chiral depsipeptide dendrimers

Article abstract of DOI:10.1002/chem.200501300

The self-assembly of chiral depsipeptide dendrons 4, which contain a cyanuric acid building block at their focal point, with the homotritopic Hamilton receptor 1 is reported. The 1:3 compositions of the resulting chiral supramolecular dendrimers, the association constants K_n, and the cooperativity of binding expressed by Scatchard plots and the Hill coefficients n_H was determined by NMR titration experiments. The most pronounced positive cooperativity was found for the complexes 1L₃ with L being the second-generation dendrons 4c-e. The least stable complexes are formed with the bulky third-generation dendrons 4f-h. Similar results are obtained by the corresponding complexation of the achiral Frechet-type first- to third-generation dendrons 3 with 1. Chiroptical investigations of 1:3 complexes of 1 and 4 reveal chirality transfer from the dendron to the Hamilton receptor as demonstrated by the appearance of new CD absorption bands at 310 nm.

Full text of DOI:10.1002/chem.200501300

FULL PAPER
Chem. Eur. J. 2006, 12, 2663 – 2679
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2663

DOI: 10.1002/chem.200501300
Self-Assembly of Chiral Depsipeptide Dendrimers
Kristine Hager, Alexander Franz, and Andreas Hirsch*[a]
Abstract: The self-assembly of chiral
depsipeptide dendrons 4, which contain
a cyanuric acid building block at their
focal point, with the homotritopic
Hamilton receptor 1 is reported. The
1:3 compositions of the resulting chiral
supramolecular dendrimers, the associ-
ation constants Kn, and the cooperativi-
ty of binding expressed by Scatchard
plots and the Hill coefficients nH was
determined by NMR titration experi-
ments. The most pronounced positive
cooperativity was found for the com-
plexes 1L3 with L being the second-
generation dendrons 4c–e. The least
stable complexes are formed with the
bulky third-generation dendrons 4 f–h.
Similar results are obtained by the cor-
responding complexation of the achiral
FrechØt-type first- to third-generation
dendrons 3 with 1. Chiroptical investi-
gations of 1:3 complexes of 1 and 4
reveal chirality transfer from the den-
dron to the Hamilton receptor as dem-
onstrated by the appearance of new
CD absorption bands at 310 nm.
Keywords: chirality · cooperativity ·
dendrimers · depsipetides · hydro-
gen bonding
Introduction
heterotritopicAB unit 2 as branching element, which con-
2
tains two Hamilton receptors as well as a complimentary cy-
anuric acid terminus. End-capping of the resulting dendritic
structures was achieved by hydrogen bonding of various cya-
nuricaicd derivatives 3.[13] For comparison we investigated
the formation of a series of 1·33 aggregates, in which the ter-
mini R of 3 consist of first to third-generation FrechØt-type
dendrons. We now report on the self-assembly and the chi-
roptical properties of the first chiral supramolecular den-
drimers 1·43 involving three depsipetide dendrons 4 of gen-
eration 1–3 containing a cyanuric acid moiety at the focal
point. The association properties of the complexes 1·43, in-
cluding the cooperativity of binding, is compared with those
of the corresponding 1·33 aggregates involving cyanuric acid
units connected by C6 spacer units. On the basis of these re-
sults we also discuss the question of the compositional and
structural diversity of supramolecular dendritic architectures
formed by the self-assembly of 1, 2, and 3,[13] which critically
depends on the amount of cooperativity.
We recently reported on the development of chiral depsi-
peptide dendrimers.[1–4] This new class of dendrimers closely
resembles the natural depsipeptides, which consist of a-hy-
droxy and amino acids connected by ester and amide linkag-
es. In this context we also reported the metal-induced chiral
folding[3] and the diastereoselective assembly of chiral RuII-
coordinated depsipeptide dendrimers[4] and investigated
their chiroptical properties. The RuII-coordinated depsipep-
tide dendrimers consisted of three 2,2’-bipyridine ligands
and involved two pairs of enantiomerically pure depsipep-
tide dendrons each, attached in a C3-symmetrical D- or L-
motif to a RuII metal center.[4] At the same time, these com-
plexes represent examples of self-assembled dendrimers,
which recently became a subject of increasing interest. The
self-assembly of purely organicdendrimers has already been
achieved by using hydrogen bonding,[5–9] electrostatic inter-
actions,[10] or hydrophobiceffetcs of amphiphilicbuilding
blocks.[11] Along these lines we developed a concept for the
self-assembly of extended dendritic architectures based on
the homotritopicHamilton receptor 1[12] as a core and the
Results andDiscussion
Syntheses: The synthesis of the homotritopicHamilton re-
ceptor 1 was carried out according to the procedure of Lehn
and co-workers.[12] As starting material for the synthesis of
[a] K. Hager, Dr. A. Franz, Prof. Dr. A. Hirsch
Institut für Organische Chemie der Friedrich-Alexander-Universität
Erlangen-Nürnberg
the chiral dendron 4 we used the tartaricacid derivatives
5
Henkestrasse 42, 91054 Erlangen (Germany)
Fax : (+49)9131-85-268-64
E-mail: andreas.hirsch@chemie.uni-erlangen.de
and 6 (see Scheme 2), and the depsipeptides 7–9, whose syn-
thesis was recently developed in our laboratory.[2–3] For the
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Self-Assembled Dendrimers
FULL PAPER
synthesis of a cyanuric acid building block suitable to under-
go binding with 1 we allowed w-bromo hexanoyl chloride 10
to react with one equivalent of 11 to give the benzyl protect-
ed precursor 12 (Scheme 1). Reaction of 12 with cyanuric
acid 13 afforded the substitution product 14, which was fi-
nally deprotected to give the building block 15. The yield of
this reaction sequence is superior to the procedure described
previously.[14]
First- and second-generation dendrons 4a–e were ob-
tained using slightly modified standard ester coupling reac-
tions (Scheme 2).[15,16] For these purposes 1-ethyl-3-(3-dime-
thylaminopropyl)carbodiimine hydrochloride (EDC·HCl) in
the presence of 4-dimethylaminopyridine (DMAP) and 1-
hydroxybenzoltriazole (HOBt) as the coupling reagent was
used. Unfortunately, the cyanuric acid building block 15 is
not soluble in the most common organic solvents and no
coupling took place in N,N’-dimethylformamide (DMF).
The reaction was therefore carried out in CH2Cl2 and pro-
ceeded heterogeneously so that a long reaction time (three
days) was required to achieve complete conversion.
For the synthesis of the third-generation dendrons 4 f–h,
the first-generation systems 4a,b were first deprotected by
hydrogenation, using 10% Pd/C as a catalyst, to give the
building blocks 16 and 17 (Scheme 3). Subsequent coupling
of 16 and 17 with the amino-terminated depsipetide den-
drons 18 and 19[4] and purification by column chromatogra-
phy afforded the dendrons 4 f–h in 26–32% yield
(Scheme 3).
The synthesis of the FrechØt-type dendrons 3[17] required
the introduction of the cyanuric acid building block 22,
which was obtained by the reaction of 1-nitrobiuret 20[18]
with 6-aminohexanol, followed by cyclization with diethyl
carbonate (Scheme 4).
The dendronization of 22 was accomplished with the pre-
cursor dendrons 30–32 containing a carboxylic acid function-
ality at the focal point (Scheme 5). For this purpose, benzyl
bromide derivatives 24, 25 and 26[19] were coupled with
methyl-3,5-dihydroxybenzoate 23 using K2CO3 as base and
[18]crown-6 as catalyst. Subsequent saponification of 27–
29[20] afforded the acids 30–32 in 78–95% yield (Scheme 5).
Finally, the dendrons 3 were ob-
tained by Steglich coupling of
30–32 with 22 (Scheme 5).
To compare the complexation
properties of the homotritopic
receptor 1 with a monorecep-
tor, we also synthesized the
model compound 33 by cou-
pling of 3,4-diethoxy-5-propoxy-
benzoiciadc with 5-amino-
N,N’-bis[6-(3,3-dimethylbutyry-
lamino)pyridine-2-yl]isophtal-
amide.[21] To enhance solubility
dimethylbutyrylamino groups
were used as termini.
Scheme 1. Synthesis of the cyanuric acid derivate 15. a) NEt3, CH2Cl2, 08C, 3 h, 93%; b) DBU, DMF, 708C,
24 h, 60%; c) 10% Pd/C, CH3OH, room temperature, 24 h, 99%.
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A. Hirsch et al.
CDCl3 display rather broad and
unresolved signals.[12] This is
due to the presence of the large
number
of
hydrogen-bond
donors and acceptors causing
the formation of intra- and in-
termolecular hydrogen bonds.
Pronounced aggregation of 1
due to intermolecular hydrogen
bonds is also the reason for the
low solubility of 1 in chloro-
form. In DMSO, where inter-
molecular associations are not
favored, the NMR spectra of 1
are well resolved. Remarkable
sharpening of the signals in
CDCl3 occurs also upon succes-
sive addition of the dendritic
cyanuric acid derivatives 3 and
4. The sharpening of the signals
is accompanied by a downfield
shift of the amide proton NH1
and NH2 of 1 and indicates the
formation of discrete 1·43 and
1·33 complexes (Figure 1).[12,13]
The 1:3 binding stoichiometry
of
the
complexes
1·43
(Scheme 6) was confirmed by
applying Jobꢁs method of con-
tinuous variation to the NMR
experiments.[12] The chemical
shift variation of NH1 (D(d)) as
a function of the mole fraction
of 4d X(4d) was monitored,
and the product of the mole
fraction X(4d)ꢀ1 and D(d) was
plotted as a function of X(1).
As an example, the Job plot
analysis of the system 1:4d is
shown in Figure 2.
Temperature-dependent
NMR spectroscopy reveals the
dynamic character of the associ-
ation of the complexes 1·43 and
1·33. As an example, the 1H
NMR spectra of a 1:10 mixture
Scheme 2. Synthesis of the first- and second-generation depsipeptide dendrons 4a–e. a) EDC, HOBt, DMAP,
CH2Cl2, room temperature, 72 h.
of 1 and 3c are represented in Figure 3. At 308C no signal is
found for the NH3 and NH3
protons of the free and
free
bound
bound ligand, respectively. Lowering the temperature below
08C leads to the appearance of two signals for the NH3
free
and NH3
protons, and indicates that the corresponding
bound
association–dissociation equilibrium is slow on the NMR
time scale. The temperature range between 0–508C repre-
sents the coalescence regime, where the signals of NH3 are
very broad and cannot be detected anymore (Figure 4). Fur-
Determination of association constants andcooperativity of
binding: The H NMR spectra of the Hamilton receptor 1 in
ther increase of the temperature causes the NH3
and
free
1
NH3
protons to give rise to one averaged signal only,
bound
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Self-Assembled Dendrimers
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Scheme 3. Synthesis of the third-generation depsipeptide dendrons 4 f–h. a) 10% Pd/C, CH3OH, room temperature, 24 h; b) EDC, HOBt, DMAP,
CH2Cl2, room temperature, 72 h.
demonstrating fast exchange processes between free and
bound ligands. The highfield shift of this signal upon in-
creasing the temperature indicates the decreasing stability
of the 1·3b3 complex.
NMR titration experiments in CDCl3 was performed. Here
the downfield shift of NH1 and NH2 of 1 was determined as
a function of the dendron concentration. In a typical experi-
ment, 0.5 mL of a 0.5 mm solution of 1 was titrated with
50 mL of a 2.5 mm solution of 3 and 4. It is important to note
that establishment of stable equilibria required some time
For the determination of the association constants and the
analysis of the cooperativity phenomena, a series of 1H
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A. Hirsch et al.
titration curves for the first-
and second-generation systems
1:43 exhibit a sigmoidal shape
with an inflection point at
about 1.5 equivalent of added 4
(Figure 5).
Scheme 4. Synthesis of cyanuric acid derivate 22. a) 6-aminohexanol, H2O, 1158C, 1 h, 40%; b) diethyl carbo-
nate, NaOEt, EtOH, 1058C, 2 h, 54 %.
A similar trend is seen for
the series of the 1:3 systems. A
sigmoidal titration curve is a
characteristic feature for a posi-
tive cooperative effect for the
subsequent binding of guest
molecules.[22,23] The association
constants for the binding of the
dendriticligands 3 and 4 were
determined using the program
Chem-Equili[24,25] and are sum-
marized in Table 1. The calcula-
tions were based on the as-
sumptions of three equilibria
(Equations (1–3)).
K1 : 1 þ L Ð 1 : L
ð1Þ
ð2Þ
ð3Þ
K2 : L þ 1 : L Ð 1 : L2
K3 : L þ 1 : L2 Ð 1 : L3
In general, the association
constants Kn, especially those
for the first and second-genera-
tion dendrons, are in good
agreement with those reported
by Lehn and co-workers for a
1L3 system, with L being a non-
dendritic cyanuric acid deriva-
tive.[12] For the case of statistical
binding, Equation (4) must be
fulfilled,[22] for which t is the
total number of binding sites
(in this case t=3).
Knþ1
Kn
nðtꢀnÞ
¼
ðn þ 1Þðtꢀn þ 1Þ
ð4Þ
However, the experimental
values for Kn+1/Kn are much
higher than those obtained
from Equation (4), which clear-
ly demonstrates the presence of
pronounced positive coopera-
Scheme 5. Synthesis of the FrØchet-type dendrons. a) K2CO3, [18]crown-6 acetone, 708C, 24 h; b) NaOH, H2O,
708C, 24 h; c) DMAP, HOBt, DCC, DMF, room temperature, 72 h.
because the intermolecular interactions between free 1
tivity. In other words the free binding energy of the dendrit-
ic ligands increases by going from the monocomplex 1L to
bis- and triscomplexes 1L2 and 1L3, respectively. This is also
reflected by the sigmoidal shape of the corresponding titra-
tion curves (Figure 5). In the case of the first and second-
needs to be overcome before the binding of the dendritic li-
1
gands can take place. As a consequence, the H NMR spec-
tra were taken not earlier than one hour after the compo-
nents were mixed. It is interesting to note that especially the
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Self-Assembled Dendrimers
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generation dendrons 4 f–4h is much less pronounced
(Figure 6). The 1 L3 fraction only becomes predominant
when 2.5 or more equivalents of 4 f–4h are added. Even
after the addition of 10 equivalents, only about 90% of 1 is
bound as 1 L3 complex.
The most straightforward presentation of the cooperativi-
ty phenomena is based on the determination of the occupan-
cy r, which is the average number of ligands bound to the
receptor, and to write the results in terms of the stepwise
equilibrium model (5).[22]
½1 Á LŠ þ 2½1 Á L2Š þ 3½1 Á L3Š
ð5Þ
r ¼
½1Š þ ½1 Á LŠ þ ½1 Á L2Š þ ½1 Á L3Š
For statistical binding r can be described by the Scatchard
[22]
equation (6),
t Á Q Á x
ð6Þ
r ¼
1 þ Q Á x
in which Q is the site binding constant and x the concentra-
tion of the added ligand. When the binding is statistical, the
Scatchard plot r/x as a function of r is a straight line. How-
ever, when there is positive cooperativity, the plot is no
longer a straight line but a concave curve. Especially the
Scatchard plots of the first- and second-generation systems
1:4a–e display very pronounced concave behavior
(Figure 7). The deviation form linearity is less pronounced
for the third-generation systems 1:4 f–g (Figure 7). This
again shows that the cooperativity for the binding of the
first- and second-generation dendrons is much higher than
that for the third-generation analogues. Qualitatively the
same behavior is found for the series 1:3.
Figure 1. Binding motif between 1 and 3 or 4 with indication of the NH
protons NH1, NH2 and NH3 (top) and 300 MHz 1H NMR spectra of 1 at
a concentration of 0.5 mm in CDCl3. a) 0 equivalents of 4a; b) 1 equiv-
alent of 4a; c) 2 equivalents of 4a; d) 3 equivalents of 4a (bottom).
generation systems 1L3 (L=4a–e), the third binding step
(3) is accompanied by the largest cooperativity. Similar be-
havior is observed for the systems 1:3a and 1:3b (Table 1).
In contrast, for the third-generation systems 1L3 (L=3c,
4 f–h) the highest cooperativity is associated with the second
binding step (2). Significantly, the binding cooperativities of
the second-generation dendrons 4c–e exhibit a pronounced
diastereoselectivity. The subsequent binding of dendron 4e
with an all-S configuration of the inner and an all-R configu-
ration of the outer tartrate layer shows a much higher coop-
erativity compared with the binding of 4c and 4d. A similar
trend is observed for the corresponding third-generation sys-
tems involving the dendrons 4 f,4g, and 4h, respectively.
The 1L3 complexes containing the third-generation den-
drons 3c and 4 f–h are less stable than their first- and
second-generation analogues.
The preferred formation of 1 L3 (L=4a–e) complexes
compared with the corresponding 1 L2 complexes also be-
comes apparent upon analysis of the distribution of 1 as free
core and within the complexes 1:Ln (n=1–3), respectively,
as a function of added dendron equivalents (Figure 6). Al-
ready at low concentrations of the added dendron, the
amount of 1 L3 (L=4a–e) complexes prevails over the other
species. After the addition of three equivalents of 4a–e, the
amount of 1 L3 complexes ranges between 88 and 94%.
After the addition of four equivalents of 4a–e, all of 1 is
bound in the corresponding 1 L3 complex. On the other
hand, the formation of 1 L3 complexes involving the third-
The quantification of the amount of cooperativity of a
given system is usually expressed by the Hill coefficient nH,
which can be obtained from the maximum of the Scatchard
plot according to Equation 7 .
rmax
tꢀrmax
nH
¼
ð7Þ
The higher the value of nH, the higher the degree of coop-
erativity; nH becomes equal to t (here t=3) for infinitely
high cooperativity. However, this has never been observed
in real systems. For both series 1:4 as well as 1:3, the highest
nH values are found for the systems with the corresponding
second-generation dendrons and the lowest nH for their
third-generation analogues (Table 1).
An open-chain Hamilton receptor, like that involved in 1,
can in principle adopt three distinct planar conformations,
namely cis–cis, cis–trans, and trans–trans (Scheme 7). Upon
binding of a barbiturate or cyanurate guest, the receptor is
always forced into an in plane cis–cis configuration. A pho-
tophysical study by Vçgtle and De Cola et al. performed on
dendrimers containing Hamilton receptor moieties in their
periphery revealed an increasing conformational restriction
and preference of the cis–cis conformation with increasing
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A. Hirsch et al.
generation number.[21] This can
be explained by increasing ster-
ical hindrance within the pe-
riphery of the dendrimer upon
going to higher generation
numbers.
These observations can be
used to explain the association
phenomena found for the sys-
tems 1:4 and 1:3, namely, very
pronounced cooperativity of
the subsequent binding of G1
and G2 dendrons. The second-
generation systems were more
cooperative than the first-gen-
eration analogues, and weak co-
operativity for the third-genera-
tion systems was found. Binding
of the first and second dendron
introduces additional sterical
constraints and forces the re-
maining Hamilton receptor
binding site to a preference for
the cis–cis conformation, which,
owing to its favorable preorga-
nization, has the highest sus-
ceptibility for the binding of an-
other cyanurate dendron. This
effect is more pronounced in
the second than in the first-gen-
eration dendrons because of the
more extended sterical require-
ments of the ligands. In the
third-generation systems, how-
ever, the dendriticligands are
so bulky that their threefold
binding becomes less favorable
again. The situation of the opti-
mal balancing of the required
sterical influence to cause the
preference of the cis–cis confor-
mation in the free sites of 1,
and self-hindrance as a conse-
quence of the ligandsꢁ sterical
demand, is best presented with
the second-generation systems
3b and 4c–e.
On the basis of these results
and considerations we wish to
address, in the following para-
graph, the question of structural
diversity in dendritic architec-
tures formed by the self-assem-
bly of 1, 2, and 3, as reported
recently.[13] Interestingly, the
size and sterical requirement of
3b is very similar to that of the
Scheme 6. Schematic representation of the chiral supramolecular dendrimers 1:43 (G I with 4a,b; G II with
4c–e and G III with 4 f–h).
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Self-Assembled Dendrimers
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Figure 2. Determination of the 1:3 stoichiometry of the system 1:4d at a
total concentration of 2.75 mm by a Job plot analysis. The y axis has been
normalized.
Figure 3. 400 MHz 1H NMR spectra of a 1:10 mixture of 1 and 3b at a
concentration of 2.75 mm in CDCl3 at ꢀ408C, ꢀ208C, 08C and 308C, re-
spectively.
Figure 5. 1H NMR titration plots of the chemical shifts of the NH1 and
NH2 protons as a function of the amount of added dendrons 4a, 4c, 4 f.
Table 1. Association constants, R factor (R), rmax, and Hill coefficients
for the systems 1:3 and 1:4.
log K1
log K2
log K3
R [%]
rmax
nH
[Lmolꢀ1
]
[Lmolꢀ1
]
[Lmolꢀ1
]
1:3a
1:3b
1:3c
1:4a
1:4b
1:4c
1:4d
1:4e
1:4 f
1:4g
1:4h
3.82
4.46
3.51
4.58
4.65
3.99
3.88
3.14
3.94
3.95
3.15
2.60
4.46
4.51
4.04
4.04
3.95
3.85
3.37
4.33
4.02
3.91
8.99
6.33
4.09
6.41
6.59
5.27
5.64
6.19
3.78
3.68
3.91
Æ0.25
Æ0.17
Æ0.23
Æ0.36
Æ0.23
Æ0.19
Æ0.22
Æ0.26
Æ0.32
Æ0.32
Æ0.22
1.92
1.98
1.40
1.82
1.84
1.85
1.86
1.93
1.08
1.02
1.29
1.78
1.94
0.88
1.54
1.58
1.61
1.63
1.80
0.56
0.52
0.75
Figure 4. Chemical shifts of the NH1-, NH2-, NH3free- and NH3
tons of a 1:10 mixture of 1 and 3b in C2D2Cl4 as a function of tempera-
pro-
bound
ture.
AB2 unit 2 that we used for the self-assembly of dendritic
supramolecular structures. This concept was based on the
idea that simple mixing of the components 1, 2 and an end
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A. Hirsch et al.
Figure 7. Scatchard plots for the systems 1 L (L=4a, 4c, 4 f).
drogen bonds. That discrete dendritic and no ill-defined pol-
ymers are indeed formed was confirmed by a variety of
methods such as thermal analysis, AFM and DOSY NMR
spectroscopy.[13] Determination of the association properties
of such structures using NMR titration experiments, like
those carried out for the systems 1:3 and 1:4, was hampered
by the complexity of the huge number of equilibria in-
volved. We already pointed out that in solution, especially
in the case of stoichiometric mixtures of 1, 2 and 3b corre-
sponding to higher generation numbers n, several objects of
different sizes coexist in equilibrium.[13] This is due to the
fact that a) based on the association constants, determined
for 1:3 and 1:4, serving as suitable models, it has to be as-
sumed that rapid association–dissociation equilibria are
present and b) at higher n the required ratio of 2 and the
Figure 6. Distribution in percent of 1 as free core and within the com-
plexes 1:Ln (n=1–3) as a function of the amount of added dendrons 4a,
4c, 4 f obtained from analysis of the titration plots using the computer
program Chem-Equili.[24,25] The total concentration of 1 within the mix-
tures is 0.5 mm.
cap such as 3b in the stoichiometric ratio of 1: (3”2nꢀ3):
(3”2n), with n=generation number, can lead to self-assem-
bled dendrimers with a regular structure such as I (n=3) for
a first-generation system (Figure 8). The driving force for
the formation of I is the exhaustive use of all possible hy-
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Self-Assembled Dendrimers
FULL PAPER
Figure 9. CD spectra of 4a–h in CHCl3 (c=0.0002 molLꢀ1).
by the schematic representation I in Figure 8. Moreover, it
has to be pointed out that, for a given stoichiometry, not
only a completely regular arrangement like that of I, but
also irregular structures such as II (n=3) (Figure 8) are
compatible with a 1:(3”2nꢀ3):(3”2n) stoichiometry and with
the exhaustive consumption of all possible hydrogen bond-
ing sites. As a matter of fact, the number of possible isomers
increases dramatically with increasing generation number.
The key question is whether and how much the formation
of I is favored over that of irregular structures such as II by
a cumulating amount of cooperativity. A delicate balance
exists between positive and negative cooperativity, as dem-
onstrated for the model dendrimers 1:3 and 1:4, namely, the
most effective preorganization of the free Hamilton receptor
binding sites and repulsive interaction between sterically
overcrowded ligands. Although this question is difficult to
address, the results presented here, as well as the fact that
the structure of 3b is very similar to that of 2, suggest that
the possibility of a cumulative cooperativity for the forma-
tion of completely regular dendrimers such as I, does exists.
Regular structures could especially prevail in the solid state.
Further work clarifying these critical questions is currently
under way in our laboratory.
Scheme 7. Planar rotamers of an open-chain Hamiliton receptor.
CD spectroscopy: The possibility to transmit chiral informa-
tion over comparatively large distances represents an ap-
pealing opportunity for applications of dendritic macromole-
cules[26] in catalysis and molecular recognition. Chirality
transfer is expected to occur from the chiral dendrons 4 to
the achiral Hamilton receptor core 1 in the 1:43 dendrimers
introduced here. The characteristic absorption bands of 1 at
about 310 nm, which are distinct from the absorption of the
aromaticgroups of the chiral dendrons 4 at about 250 nm,
should be highly diagnosticfor the investigation of a chirali-
ty transfer process, since they should lead to new Cotton ef-
fects in the CD spectra of the supramolecular dendrimers
1:43. The CD spectra of the free dendrons 4 recorded in
CHCl3 are shown in Figure 9. As expected, the Cotton ef-
fects increase with increasing generation number and conse-
Figure 8. Schematic representation of supramolecular dendrimers com-
posed of 1, 2 and an end cap such as 3b in a 1: (3”2nꢀ3): (3”2n) stoichi-
ometry. Left: I completely regular structure (n=3). Right: example for
an irregular structure II (n=3).
end cap 3 differs only slightly and approaches a 1:1 limit. It
has to be stated that not all objects, at least in solution, can
be identical and cannot exhibit the perfect shape suggested
Chem. Eur. J. 2006, 12, 2663 – 2679
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2673

A. Hirsch et al.
ture. For example, the CD spectrum of 1:4h3 is characterized
by two negative Cotton effects, below 280 nm and at
310 nm, whereas those of its diastereoisomers 1:4 f3 and
1:4g3 display one positive and one negative Cotton effect
each. The CD spectra of 1:1 complexes of 4 with the core 33
show similar characteristics as those of the corresponding
1:43 analogues (Figure 11). These characteristics include a)
almost no Cotton effects at 310 nm for the first-generation
dendrons, b) increasing Cotton effects with an increasing
generation number, c) mirror image behavior for enantio-
meric complexes, and d) the same characteristic shape of
the diastereoisomericocmplexes involving dendrons with
mixed configurations. This demonstrates that the chiroptical
properties of 1:43 are not due to the diastereoselective for-
mation of chiral foldamers, such as the preferred C3 sym-
metrical conformers of 1 within the 1:3 complexes, but are
due to statistical chirality transfer from the chiral dendrons
only.
Figure 10. CD spectra of the 1:3 assemblies between 1 and 4c–h in
CHCl3 (c1 =0.00008 molLꢀ1).
quently with an increasing number of stereogenic centers
[2]
and aromaticchromophores.
Pairs of enantiomers such as
Conclusion
4 f and 4g give rise to CD spectra which represent perfect
mirror images of each other.
The self-assembly of chiral depsipeptide dendrons 4, which
contain a cyanuric acid building block at their focal point,
with the homotritopicHamilton receptor 1 leads to the for-
mation of the supramolecular complexes 1:43. The subse-
quent binding of the dendrons to the core shows an overall
positive cooperativity for all cases. The cooperativity is most
pronounced for the binding of the second-generation den-
drons 4c–e. This is expressed, for example, by the magni-
tude of the association constants of the second and third
complexation step and the high Hill coefficients nH deter-
mined by NMR titration experiments. Significantly, the
binding of the dendrons 4 to the receptor 1 is also diastereo-
selective. This is demonstrated, for example, by the fact that
the subsequent binding of dendron 4e with an all-S configu-
ration of the inner and an all-R configuration of the outer
tartrate layer shows a much higher cooperativity compared
to the binding of 4c and 4d with all-R or all-S-configura-
tions of all stereogenicecntres. The formation of the 1:43
complexes with the third-generation dendrons 4 f–h shows
the lowest cooperativity. This is due to the fact that these
dendrons are very bulky, disfavoring the binding of the third
dendron. In the case of the second-generation dendrons 4c–
e, the optimum balance between the preorganization of the
Hamilton receptor into the favorable cis–cis conformation,
caused by the subsequent binding of the first and second
dendron and the steric overcrowding caused by their accu-
mulation at receptor 1, is guaranteed. Similar results are ob-
tained by the corresponding complexation of the achiral
FrechØt-type dendrons 3 with 1. Chiroptical investigations of
1:3 complexes of 1 and 4 reveal chirality transfer from the
dendron to the Hamilton receptor, as demonstrated by the
appearance of new CD absorptions at 310 nm. The com-
plexes 1:43 represent the first examples of chiral supramolec-
ular dendrimers whose construction is provided by comple-
mentary hydrogen bonding motifs.
The CD spectra of the chiral supramolecular dendrimers
1:43 are shown in Figure 10. Significantly, new Cotton effects
were indeed observed in the region of the electronic absorp-
tion of the Hamilton receptor 1 at 310 nm for the case of
the second- and third-generation systems 1 L3 (L=4c–h).
However, no Cotton effects in the absorption region of 1
were observed for the first-generation systems 1 L3 (L=
4a,b). This indicates that only a very weak chiral surround-
ing is provided by the two stereogeniccenters of the first-
generation dendrons 4a and 4b.
Complexes 1 L3, involving second- and third-generation
dendrons of opposite configuration such as 1:4c3 and 1:4d3,
lead to CD spectra with mirror-image behavior (Figure 10).
On the other hand, the CD spectra of diastereoisomeric
complexes such as 1:4e3 or 1:4h3 exhibit a different struc-
Figure 11. CD spectra of the 1:1 assemblies between 33 and 4c–h in
CH2Cl2 (c33 =0.0001 molLꢀ1).
2674
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 2663 – 2679

Self-Assembled Dendrimers
FULL PAPER
2938, 1730, 1690, 1632, 1466, 1417, 1381, 1319, 1262, 1213, 1058, 925, 790,
733, 551, 433 cmꢀ1; elemental analysis calcd (%) for C9H13N3O5: C 44.44,
H 5.39, N 17.28; found: C 44.35, H 5.61, N 17.18.
Experimental Section
General remarks: All chemicals were obtained from Sigma-Aldrich and
Acros Organics or were prepared according to known literature proce-
dures. The preparation of 5–9, 18, and 19[2–4] was described in previous
communications. The solvents were purified by distillation. Reactions
were monitored by thin-layer chromatography (TLC) using Riedel-de-
Han silica gel 60 F254 aluminium foils, detection by UV illumination. 1H
and 13C NMR spectra were recorded on Bruker Advance 300, JEOL
JNM EX 400, JEOL JNM GX 400 and JEOL A 500 NMR spectrome-
ters. The chemical shifts are given in ppm relative to TMS or the solvent
peak as a standard reference. The resonance multiplicities are indicated
as s (singlet), d (doublet), t (triplet), q (quartet) and m (multiplet), unre-
solved signals as brm. Mass spectra were measured with a Micromass
Lab Spec(FAB) on a Finnigan MAT 900 spectrometer with 3-nitroben-
zylalcohol as the matrix. IR spectra were recorded on React IR-1000
ASI Applied Systems (ATR-DiComp-Detector) on a diamond crystal.
Circular dichroism (CD) measurements were carried out on a Jasco J 715
and Jasco J 810 machine using optical grade solvents and quartz glass
cuvettes with a 2 mm path length. Optical rotations were measured on a
Perkin Elmer 341 polarimeter. UV spectroscopy was performed using a
Shimadzu UV-3102 spectrophotometer. Elemental analysis succeeded by
combustion and gas chromatographical analysis was performed with an
EA 1110 CHNS analyser (CEInstruments). Products were isolated by
flash column chromatography (FC) (silica gel 60, particle size 0.04–
0.063 mm, Merck).
General procedure for the preparation of the esters 4a–e: The carboxylic
acid (1.6 mmol), 4-dimethylaminopyridine (DMAP, 1.6 mmol) and 1-hy-
droxybenzoltriazole (HOBt, 1.6 mmol) were added to a solution of the
alcohol (1.6 mmol) in CH2Cl2 (100 mL). 1-(3-Dimethylaminopropyl)-3-
ethylcarbodiimide hydrochloride (EDC·HCl) (1.6 mmol) was added all at
once at room temperature and the suspension was stirred for 72 h. The
solution was washed with 10% aqueous HCl (1”100 mL) and with satu-
rated aqueous NaHCO3 (3”150 mL) and then dried over MgSO4. After
evaporation of the solvent the crude product was purified by column
chromatography.
Compound4a : Compound 4a was synthesized according to the general
procedure from dendron 5 (720 mg, 1.66 mmol) and 1-(5-carboxypentyl)-
1,3,5-triazin-2,4,6-trion (15) (400 mg, 1.66 mmol). The crude product was
purified by column chromatography (silica, CH2Cl2/CH3OH, 15:1). Yield:
500 mg (46%) as a white solid; m.p. 808C; 1H NMR (400 MHz, CDCl3):
d=1.27 (m, 2H, CH2), 1.53 (m, 4H, CH2), 2.20 (m, 2H; CH2), 3.73 (m,
2
2H; CH2N), 5.03 (d, J=12 Hz, 1H; CH2 Bn), 5.09 (d, 2J=12 Hz, 1H;
ꢀ
CH2 Bn), 5.16 (d, J=12 Hz, 1H; CH2 Bn), 5.20 (d, 2J=12 Hz, 1H;
2
ꢀ
ꢀ
CH2 Bn), 5.75 (d, J=2.8 Hz, 1H; *CH), 5.85 (d, 3J=2.8 Hz, 1H; *CH),
3
ꢀ
7.09 (m, 3H; Bn), 7.10 (m, 2H; Bn), 7.29 (m, 5H; Bn), 7.33 (m, 2H; Bz),
7.57 (m, 1H; Bz), 7.89 (m, 2H; Bz), 8.85 ppm (brm, 2H; NH); 13C NMR
(100.6 MHz, CDCl3): d=24.8, 25.5, 27.3 (CH2), 33.6 (CH2COO), 41.6
ꢀ
(CH2N), 67.7, 67.8 (CH2 Bn), 70.7, 71.2 (*CH), 128.2, 128.3, 128.4, 128.5,
128.6, 130.1 (Ph), 133.6, 134.5, 134.8 (q-Ph), 147.9, 149.1, 165.0, 165.6,
165.7, 172.1 ppm (C=O); IR (ATR): nmax =3227, 2972, 2362, 2339, 1737,
1455, 1374, 1231, 1092, 714, 695 cmꢀ1; MS (FAB): m/z (%): 660 [M]+;
UV/Vis (CH3OH): l(e)=264 (1000), 231.5 nm (16000); elemental analy-
sis calcd (%) for C34H33N3O11 (659.21): C 61.91, H 5.04, N 6.37; found: C
61.87, H 5.14, N 6.32; [a]2D0 =+30.0 (c=0.0968, CH2Cl2).
Benzyl-6-bromohexanoate (12): Freshly distilled benzyl alcohol (2.32 mL,
18.92 mmol) was dissolved in CH2Cl2 and triethylamine (NEt3, 2.63 mL,
18.92 mmol) was added. The mixture was cooled to 08C and 6-bromohex-
anoyl chloride (2.90 mL, 18.92 mmol) was added dropwise. After three
hours the solution was washed with 10% aqueous HCl (1”100 mL) and
with saturated aqueous NaHCO3 (3”150 mL) and then dried over
MgSO4. The solvent was evaporated and the product dried in vacuo.
Yield: 4.97 g (93%) as a colorless oil; 1H NMR (400 MHz, CDCl3): d=
Compound4b : Compound 4b was synthesized according to the general
procedure from dendron 6 (720 mg, 1.66 mmol) and 1-(5-carboxypentyl)-
1,3,5-triazin-2,4,6-trion (15) (400 mg, 1.66 mmol). The crude product was
purified by column chromatography (silica, CH2Cl2/CH3OH, 15:1). Yield:
450 mg (41%) as a white solid; m.p. 79 C; 1H NMR (400 MHz, CDCl3):
1.41 (m, 2H; CH2), 1.65 (m, 2H; CH2), 1.83 (m, 2H; CH2), 2.37 (t, 3J=
3
ꢀ
7.7 Hz, 2H; CH2CO), 3.39 (t, J=7.7 Hz, 2H; CH2Br), 5.10 (s, 2H; CH2
Bn), 7.37 ppm (m, 5H; Bn); 13C NMR (100.6 MHz, CDCl3): d=23.9,
ꢀ
27.5, 32.2, 33.4, 33.9 (CH2), 66.1 (CH2 Bn), 128.1, 128.2, 128.5 (Ph), 135.9
d=1.26 (m, 2H; CH2), 1.50 (m, 4H; CH2), 2.20 (m, 2H; CH2), 3.73 (m,
(q-Ph), 173.1 ppm (C=O); MS (FAB): m/z (%): 285 [M]+; IR (ATR):
nmax =2941, 2868, 2362, 2343, 1733, 1455, 1382, 1355, 1254, 1212, 1162,
976, 737, 699 cmꢀ1; elemental analysis calcd (%) for C13H17BrO2: C 54.75,
H 6.01; found: C 54.63, H 6.2.
2
2H; CH2N), 5.03 (d, J=12 Hz, 1H; CH2 Bn), 5.10 (d, 2J=12 Hz, 1H;
ꢀ
CH2 Bn), 5.16 (d, J=12 Hz, 1H; CH2 Bn), 5.20 (d, 2J=12 Hz, 1H;
2
ꢀ
ꢀ
CH2 Bn), 5.75 (d, J=2.8 Hz, 1H; *CH), 5.85 (d, 3J=2.8 Hz, 1H; *CH),
3
ꢀ
7.09 (m, 3H; Bn), 7.10 (m, 2H; Bn), 7.29 (m, 5H; Bn), 7.33 (m, 2H; Bz),
7.57 (m, 1H; Bz), 7.89 (m, 2H; Bz), 8.93 ppm (brm, 2H; NH); 13C NMR
(100.6 MHz, CDCl3): d=23.4, 25.1, 26.7 (CH2), 32.8 (CH2COO), 39.9
Benzyl-6-(2,4,6-trioxo-1,3,5-triazinan-1-yl)hexanoate (14): Compound 12
(2.84 g, 10 mmol) and cyanuric acid (6.50 g, 50 mmol) were dissolved in
dry DMF (50 mL). 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU, 1.5 mL,
10 mmol) was added dropwise to the solution. The mixture was heated to
708C and stirred over night. The solvent was evaporated and the crude
mixture purified by column chromatography (silica, CH2Cl2/CH3OH,
96:4). Yield: 2.00 g (60%) as a white solid; m.p. 1498C; 1H NMR
(400 MHz, [D6]DMSO): d=1.24 (m, 2H; CH2), 1.51 (m, 4H; CH2), 2.33
ꢀ
(CH2N), 67.8, 68.1 (CH2 Bn), 70.8, 71.1 (*CH), 128.2, 128.3, 128.4, 128.5,
128.6, 128.7, 129.9 (Ph), 133.8, 134.3, 134.7 (q-Ph), 165.0, 165.7, 165.8,
172.1 ppm (C=O); IR (ATR): nmax =3225, 2972, 2365, 2339, 1734, 1457,
1374, 1230, 1092, 718, 695 cmꢀ1; MS (FAB): m/z (%): 660 [M]+; UV/Vis
(CH3OH): l(e)=264.5 (1000), 231.5 nm (13000); elemental analysis calcd
(%) for C34H33N3O11: C 61.91, H 5.04, N 6.37; found: C 61.39, H 5.30, N
6.10; [a]2D0 =ꢀ31.0 (c=1.2020, CH2Cl2).
3
3
(t, J=7.7 Hz, 2H; CH2CO), 3.59 (t, J=7.7 Hz, 2H; CH2N), 5.07 (s, 2H;
CH2 Bn), 7.34 (m, 5H; Bn), 11.39 ppm (brm, 2H; NH); 13C NMR
(100.6 MHz, [D6]DMSO): d=24.1, 25.5, 27.0, 33.3, 38.9 (CH2), 65.3
ꢀ
Compound4c : Compound 4c was synthesized according to the general
procedure from dendron 7 (755 mg, 0.57 mmol) and 1-(5-carboxypentyl)-
1,3,5-triazin-2,4,6-trion (15) (140 mg, 0.57 mmol). The crude product was
purified by column chromatography (silica, CH2Cl2/CH3OH, 15:1). Yield:
590 mg (65%) as a white solid; m.p. 758C; 1H NMR (400 MHz, CDCl3):
ꢀ
(CH2 Bn), 127.9, 128.0, 128.5 (Ph), 136.3 (q-Ph), 148.7, 149.8, 172.7 ppm
(C=O); IR (ATR): nmax =3030, 2949, 2837, 2362, 2343, 1779, 1729, 1664,
1490, 1428, 1243, 1173, 830, 760, 695 cmꢀ1; MS (FAB): m/z (%): 334
[M]+; elemental analysis calcd (%) for C16H19N3O5: C 57.65, H 5.75, N
12.61; found: C 57.71, H 5.81, N 12.52.
d=1.43 (m, 22H; CH2), 2.14 (m, 6H; CH2COO), 3.20 (m, 6H; CH2N),
2
3.71 (brm, 1H; NH), 5.02 (d, J=5.5 Hz, 1H; CH2 Bn), 5.05 (d, 2J=
ꢀ
2
5.5 Hz, 1H; CH2 Bn), 5.09 (d, J=6.5 Hz, 1H; CH2 Bn), 5.12 (d, 2J=
ꢀ
ꢀ
1-(5-Carboxypentyl)-1,3,5-triazin-2,4,6-trion
(15):
Compound
14
2
6.5 Hz, 1H; CH2 Bn), 5.15 (d, J=6.0 Hz, 1H; CH2 Bn), 5.18 (d, 2J=
ꢀ
ꢀ
(1500 mg, 4.5 mmol) was dissolved in CH3OH (150 mL) and 10% Pd/C
(150 mg) was added. This suspension was subjected to hydrogenation
until no more hydrogen was consumed. The Pd-C was filtered over
Celite and CH3OH was evaporated. The product was dried in vacuo.
Yield 1100 mg (99%) as a white solid; m.p. 2138C; 1H NMR (400 MHz,
[D6]DMSO): d=1.33 (m, 2H; CH2), 1.65 (m, 4H; CH2), 2.30 (t, 3J=
7.7 Hz, 2H; CH2CO), 3.71 (t, 3J=7.7 Hz, 2H; CH2N), 11.63 ppm (brm,
2H; NH); 13C NMR (100.6 MHz, [D6]DMSO): d=24.5, 25.9, 27.4, 33.8,
39.0 (CH2), 149.0, 150.2, 174.8 ppm (C=O); IR (ATR): nmax =3476, 3214,
2
6.0 Hz, 1H; CH2 Bn), 5.22 (d, J=4.0 Hz, 1H; CH2 Bn), 5.24 (d, 2J=
ꢀ
ꢀ
3
3
ꢀ
4.0 Hz, 1H; CH2 Bn), 5.73 (d, J=3.0 Hz, 1H; *CH), 5.79 (d, J=3.0 Hz,
1H; *CH), 5.81 (d, 3J=3.0 Hz, 1H; *CH), 5.82 (d, 3J=3.0 Hz, 1H;
3
3
*CH), 5.89 (d, J=3.0 Hz, 1H; *CH), 5.91 (d, J=3.0 Hz, 1H; *CH), 6.58
(brm, 1H; NH), 7.09 (m, 6H; Bn), 7.15 (m, 4H; Bn), 7.27 (m, 10H; Bn),
7.38 (m, 6H; Ph), 7.53 (m, 3H; Bz), 7.91 (m, 4H; Bz), 8.01 (m, 2H; Bz),
9.35 ppm (s, 2H; NH); 13C NMR (100.6 MHz, CDCl3): d=23.9, 24.0,
24.1, 25.2, 25.6, 25.82, 25.84, 27.1, 28.7, 28.8 (CH2), 33.1, 33.2, 33.4
Chem. Eur. J. 2006, 12, 2663 – 2679
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2675

A. Hirsch et al.
1
ꢀ
(CH2COO), 39.2, 39.3, 41.2 (CH2N), 67.7, 67.9 (CH2 Bn), 70.7, 71.1, 71.2,
166 C; H NMR (300 MHz, [D6]DMSO): d=1.27 (m, 2H; CH2), 1.51 (m,
4H; CH2), 2.33 (t, 3J=7.7 Hz, 2H; CH2CO), 3.60 (t, 3J=7.7 Hz, 2H;
CH2N), 5.58 (brm, 1H; *CH), 5.70 (brm, 1H; *CH), 7.57 (m, 2H, Bz),
7.71 (m, 1H, Bz), 7.94 (m, 2H, Bz), 11.59 ppm (brm, 2H, NH); 13C NMR
(100.6 MHz, [D6]DMSO): d=25.9, 27.5, 28.9, 35.0, 42.5 (CH2), 129.9,
131.3, 131.4 (Ph), 135.0 (q-Ph), 150.9, 152.0, 167.6, 174.8 ppm (C=O); IR
(ATR): nmax =3231, 2972, 2362, 2343, 1737, 1459, 1374, 1263, 1231, 1096,
72.3 (*CH), 128.2, 128.3, 128.31, 128.42, 128.6, 128.7, 129.7, 129.9, 130.0,
133.6, 133.8, 134.4, 134.7, 134.8 (Ph), 147.9, 149.0, 164.9, 165.0, 165.6,
165.7, 166.2, 166.3, 171.8, 172.1, 172.2, 172.3 ppm (C=O); IR (ATR):
nmax =3273, 2972, 2362, 2343, 1733, 1698, 1540, 1455, 1378, 1231, 1092,
953, 714 cmꢀ1; MS (FAB): m/z (%): 1539 [M]+; UV/Vis (CH3OH): l
(e)=264 (3000), 232 nm (39000); elemental analysis calcd (%) for
C84H87N5O25: C 64.01, H 5.44, N 4.55; found: C 63.64, H 5.57, N 4.45;
[a]2D0 =+20 (c=0.1106, CH2Cl2).
764, 714 cmꢀ1
.
Compound17 : Compound 17 was synthesized according to the general
procedure with compound 4b (400 mg, 0.46 mmol) and 10% Pd/C
(130 mg) in CH3OH (70 mL). Yield: 290 mg (99%) as a white solid; 1H
NMR (300 MHz, [D6]DMSO): d=1.27 (m, 2H; CH2), 1.51 (m, 4H;
CH2), 2.33 (t, 3J=7.7 Hz, 2H; CH2CO), 3.60 (t, 3J=7.7 Hz, 2H; CH2N),
5.58 (brm, 1H, *CH), 5.70 (brm, 1H, *CH), 7.57 (m, 2H, Bz), 7.71 (m,
1H, Bz), 7.94 (m, 2H, Bz), 11.59 ppm (brm, 2H, NH); 13C NMR
(100.6 MHz, [D6]DMSO): d=25.9, 27.5, 28.9, 35.0, 42.5 (CH2), 129.9,
131.3, 131.4 (Ph), 135.0 (q-Ph), 150.9, 152.0, 167.6, 174.8 ppm (C=O); IR
(ATR): nmax =3230, 2972, 2365, 2343, 1739, 1460, 1374, 1268, 1231, 1096,
Compound4d : Compound 4d was synthesized according to the general
procedure from dendron 8 (650 mg, 0.49 mmol) and 1-(5-carboxypentyl)-
1,3,5-triazin-2,4,6-trion ((15) 120 mg, 0.49 mmol). The crude product was
purified by column chromatography (silica, CH2Cl2/CH3OH, 15:1). Yield:
450 mg (59%) as a white solid; m.p. 758C; 1H NMR (400 MHz, CDCl3):
d=1.44 (m, 22H; CH2), 2.14 (m, 6H; CH2COO), 3.20 (m, 6H; CH2N),
2
3.71 (brm, 1H; NH), 5.02 (d, J=5.5 Hz, 1H; CH2 Bn), 5.05 (d, 2J=
ꢀ
2
5.5 Hz, 1H; CH2 Bn), 5.08 (d, J=6.5 Hz, 1H; CH2 Bn), 5.12 (d, 2J=
ꢀ
ꢀ
2
6.5 Hz, 1H; CH2 Bn), 5.15 (d, J=6.0 Hz, 1H; CH2 Bn), 5.18 (d, 2J=
ꢀ
ꢀ
2
6.0 Hz, 1H; CH2 Bn), 5.22 (d, J=4.0 Hz, 1H; CH2 Bn), 5.24 (d, 2J=
ꢀ
ꢀ
768, 714 cmꢀ1
.
3
3
ꢀ
4.0 Hz, 1H; CH2 Bn), 5.74 (d, J=3.0 Hz, 1H; *CH), 5.79 (d, J=3.0 Hz,
General procedure for the preparation of compounds 4 f–h: The diacid
(0.35 mmol) was dissolved in CH2Cl2 (50 mL) and HOBt (0.70 mmol)
was added. The solution was cooled to 08C. In another vessel the amine
(0.70 mmol) was dissolved in CH2Cl2 (50 mL) and after cooling the solu-
tion to 08C NEt3 (0.70 mmol) was added. Both solution were unified and
EDC·HCl (0.70 mmol) was added. The mixture was stirred for 48 h. The
solution was washed with 10% aqueous HCl (1”100 mL) and with satu-
rated aqueous NaHCO3 (3”150 mL) and then dried over MgSO4. After
evaporation of the solvent the crude product was purified by column
chromatography.
1H; *CH), 5.81 (d, 3J=3.0 Hz, 1H; *CH), 5.82 (d, 3J=3.0 Hz, 1H;
3
3
*CH), 5.89 (d, J=3.0 Hz, 1H; *CH), 5.91 (d, J=3.0 Hz, 1H; *CH), 6.58
(brm, 1H; NH), 7.09 (m, 6H; Bn), 7.15 (m, 4H; Bn), 7.27 (m, 10H; Bn),
7.38 (m, 6H; Ph), 7.53 (m, 3H; Bz), 7.91 (m, 4H; Bz), 8.01 (m, 2H; Bz),
9.35 ppm (s, 2H; NH); 13C NMR (100.6 MHz, CDCl3): d=23.8, 24.0,
24.1, 25.2, 25.6, 25.82, 25.84, 27.1, 28.7, 28.8 (CH2), 33.1, 33.2, 33.4
ꢀ
(CH2COO), 39.2, 39.3, 41.2 (CH2N), 67.7, 67.9 (CH2 Bn), 70.7, 71.1, 71.2,
72.3 (*CH), 128.2, 128.3, 128.31, 128.42, 128.5, 128.7, 129.7, 129.9, 130.0,
133.6, 133.8, 134.4, 134.7, 134.8 (Ph), 147.9, 149.0, 164.9, 165.0, 165.6,
165.7, 166.2, 166.3, 171.8, 172.1, 172.2, 172.3 ppm (C=O); IR (ATR):
nmax =3250, 2972, 2362, 2339, 1733, 1698, 1540, 1455, 1378, 1216, 1092,
958, 714 cmꢀ1; MS (FAB): m/z (%): 1539 [M]+; UV/Vis (CH3OH): l
(e)=264 (3000), 232 nm (39000); elemental analysis calcd (%) for
C84H87N5O25: C 64.01, H 5.44, N 4.55; found: C 63.84, H 5.57, N 4.54;
[a]2D0 =ꢀ20 (c=0.1098, CH2Cl2).
Compound4 f : Compound 4 f was synthesized according to the general
procedure from dendron 18 (1.00 g, 0.70 mmol) and compound 16
(177 mg, 0.35 mmol). The crude product was purified by column chroma-
tography (silica, CH2Cl2/CH3OH, 30:1). Yield: 360 mg (32%) as a white
solid; m.p. 78 C; 1H NMR (400 MHz, CDCl3): d=1.44 (m, 42H; CH2),
2.04 (m, 14H; CH2COO), 3.20 (m, 14H; CH2N), 3.71 (brm, 2H; NH),
Compound4e : Compound 4e was synthesized according to the general
procedure from dendron 9 (650 mg, 0.49 mmol) and 1-(5-carboxypentyl)-
1,3,5-triazin-2,4,6-trion (15) (120 mg, 0.49 mmol). The crude product was
purified by column chromatography (silica, CH2Cl2/CH3OH, 15:1). Yield:
560 mg (74%) as a white solid; m.p. 748C; 1H NMR (400 MHz, CDCl3):
ꢀ
ꢀ
5.05 (m, 8H; CH2 Bn), 5.20 (m, 8H; CH2 Bn), 5.74 (m, 10H; *CH),
5.89 (m, 4H; *CH), 6.61 (brm, 4H; NH), 7.09 (m, 12H; Ph), 7.14 (m,
8H; Bn), 7.27 (m, 20H; Bn), 7.38 (m, 14H; Bz), 7.53 (m, 7H; Bz), 7.91
(m, 8H; Bz), 8.01 (m, 6H; Bz), 9.53 ppm (s, 2H; NH); 13C NMR
(100.6 MHz, CDCl3): d=23.8, 24.7, 25.3, 25.5, 25.7, 26.8,28.7, 28.8 (CH2),
33.0, 33.2, 33.3, 33.7 (CH2COO), 38.8, 39.0, 39.2, 41.0 (CH2N), 67.7, 67.9
d=1.43 (m, 22H; CH2), 2.13 (m, 6H; CH2COO), 3.20 (m, 6H; CH2N),
2
3.73 (brm, 1H; NH), 5.02 (d, J=5.5 Hz, 1H; CH2 Bn), 5.05 (d, 2J=
ꢀ
2
5.5 Hz, 1H; CH2 Bn), 5.09 (d, J=6.5 Hz, 1H; CH2 Bn), 5.12 (d, 2J=
ꢀ
(CH2 Bn), 70.7, 71.1, 71.2, 72.3, 72.9, 73.1 (*CH), 128.4, 128.5, 128.6,
ꢀ
ꢀ
2
6.5 Hz, 1H; CH2 Bn), 5.15 (d, J=6.0 Hz, 1H; CH2 Bn), 5.18 (d, 2J=
128.7, 128.8, 129.0, 130.2, 133.8, 134.0, 134.2, 134.6, 134.9, (Ph), 148.2,
149.4, 165.31, 165.33, 165.36, 165.9, 166.0, 166.5, 166.6, 166.7, 172.0, 172.5,
172.6 ppm (C=O); IR (ATR): nmax =3277, 2941, 2343, 1729, 1687, 1540,
1455, 1254, 1212, 1092, 1027, 953, 714 cmꢀ1; MS (FAB): m/z (%): 3297
[M]+; UV/Vis (CH3OH): l (e) =264 (8000), 232 nm (83000);elemental
analysis calcd (%) for C178H183N9O53·CH2Cl2: C 63.58, H 5.51, N 3.73;
found: C 63.46, H 5.60, N 3.82; [a]2D0 =+18 (c=0.200, CH2Cl2).
ꢀ
ꢀ
2
6.0 Hz, 1H; CH2 Bn), 5.22 (d, J=4.0 Hz, 1H; CH2 Bn), 5.24 (d, 2J=
ꢀ
ꢀ
3
3
ꢀ
4.0 Hz, 1H; CH2 Bn), 5.73 (d, J=3.0 Hz, 1H; *CH), 5.79 (d, J=3.0 Hz,
1H; *CH), 5.81 (d, 3J=3.0 Hz, 1H; *CH), 5.82 (d, 3J=3.0 Hz, 1H;
3
3
*CH), 5.89 (d, J=3.0 Hz, 1H; *CH), 5.91 (d, J=3.0 Hz, 1H; *CH), 6.48
(brm, 1H; NH), 7.09 (m, 6H; Bn), 7.14 (m, 4H; Bn), 7.28 (m, 10H; Bn),
7.38 (m, 6H; Ph), 7.54 (m, 3H; Bz), 7.90 (m, 4H; Bz), 8.01 (m, 2H; Bz),
9.05 ppm (s, 2H; NH); 13C NMR (100.6 MHz, CDCl3): d=23.9, 24.0,
24.1, 25.3, 25.6, 25.8, 27.1, 28.8, 28.9 (CH2), 33.1, 33.2, 33.4 (CH2COO),
Compound4g : Compound 4g was synthesized according to the general
procedure from dendron 19 (370 mg, 0.26 mmol) and compound 17
(63 mg, 0.35 mmol). The crude product was purified by column chroma-
tography (silica, CH2Cl2/CH3OH, 30:1). Yield: 110 mg (26%) as a white
solid; m.p. 79 C; 1H NMR (400 MHz, CDCl3): d=1.44 (m, 42H; CH2),
2.04 (m, 14H; CH2COO), 3.20 (m, 14H; CH2N), 3.71 (brm, 2H; NH),
ꢀ
39.2, 39.3, 41.3 (CH2N), 67.7, 67.9 (CH2 Bn), 70.7, 71.1, 72.3 (*CH),
127.0, 128.2, 128.3, 128.4, 128.6, 130.0, 133.6, 133.9, 134.4, 134.7 (Ph),
147.6, 149.0, 165.0, 165.6, 165.7, 166.2, 166.3, 171.8, 172.1, 172.3,
172.33 ppm (C=O); IR (ATR): nmax =3253, 2972, 2363, 2336, 1733, 1699,
1540, 1458, 1378, 1212, 1092, 954, 714 cmꢀ1; MS (FAB): m/z (%): 1539
[M]+; UV/Vis (CH3OH): l(e)=264 (3000), 232 nm (39000); elemental
analysis calcd (%) for C84H87N5O25: C 64.01, H 5.44, N 4.55; found: C
63.84, H 5.49, N 4.43; [a]2D0 =+16 (c=0.1000, CH2Cl2).
ꢀ
ꢀ
5.05 (m, 8H; CH2 Bn), 5.20 (m, 8H; CH2 Bn), 5.74 (m, 10H; *CH),
5.89 (m, 4H; *CH), 6.61 (brm, 4H; NH), 7.09 (m, 12H; Ph), 7.14 (m,
8H; Bn), 7.27 (m, 20H; Bn), 7.38 (m, 14H; Bz), 7.53 (m, 7H; Bz), 7.91
(m, 8H; Bz), 8.01 (m, 6H; Bz), 9.53 ppm (s, 2H; NH); 13C NMR
(100.6 MHz, CDCl3): d=23.8, 24.7, 25.3, 25.5, 25.7, 26.8,28.7, 28.8 (CH2),
33.0, 33.2, 33.3, 33.7 (CH2COO), 38.8, 39.0, 39.2, 41.0 (CH2N), 67.7, 67.9
General procedure for the preparation of compounds 16 and 17: The Bn
ester was dissolved in CH3OH (50 mL) and 30 mass percent of Pd/C
(10% Pd) were added. This suspension was subjected to hydrogenation
until no more hydrogen was consumed. The Pd/C was filtered over Celite
and CH3OH was evaporated. The product was dried in vacuo.
ꢀ
(CH2 Bn), 70.7, 71.1, 71.2, 72.3, 72.9, 73.1 (*CH), 128.4, 128.5, 128.6,
128.7, 128.8, 129.0, 130.2, 133.8, 134.0, 134.2, 134.6, 134.9, (Ph), 148.2,
149.4, 165.31, 165.33, 165.36, 165.9, 166.0, 166.5, 166.6, 166.7, 172.0, 172.5,
172.6 ppm (C=O); IR (ATR): nmax =3296, 2941, 2343, 1733, 1687, 1540,
1455, 1254, 1216, 1197, 1127, 957, 714 cmꢀ1; MS (FAB): m/z (%): 3297
[M]+; UV/Vis (CH3OH): l(e)=264.5 (8000), 231.5 nm (83000); elemen-
Compound16 : Compound 16 was synthesized according to the general
procedure with compound 4a (300 mg, 0.46 mmol) and 10% Pd/C
(100 mg) in CH3OH (70 mL). Yield: 217 mg (99%) as a white solid; m.p.
2676
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 2663 – 2679

Self-Assembled Dendrimers
FULL PAPER
tal analysis calcd (%) for C178H183N9O53·CH2Cl2: C 63.58, H 5.51, N 3.73;
d=69.05 (CH2Bn) 106.11, 107.55, 127.23, 127.45, 128.00, 132.45, 136.30,
158.96 (Ph), 166.44 ppm (C=O); IR (ATR): nmax =3208, 3110, 2945, 1687,
1594, 1444, 1420, 1378, 1343, 1301, 1274, 1216, 1162, 1058, 1027, 930, 903,
880, 849, 737, 695 cmꢀ1; MS (FAB): m/z (%): 335 [M]+; elemental analy-
sis calcd (%) for C21H18O4 (334.37): C 75.43, H 5.43; found: C 75.19, H
5.55.
found: C 63.46, H 5.68, N 3.76; [a]2D0 =ꢀ18 (c=0.500, CH2Cl2).
Compound4h : Compound 4h was synthesized according to the general
procedure from dendron 18 (800 mg, 0.56 mmol) and compound 17
(134 mg, 0.28 mmol). The crude product was purified by column chroma-
tography (silica, CH2Cl2/CH3OH, 30:1). Yield: 320 mg (32%) as a white
solid; m.p. 78 C; 1H NMR (400 MHz, CDCl3): d=1.44 (m, 42H; CH2),
2.04 (m, 14H; CH2COO), 3.20 (m, 14H; CH2N), 3.71 (brm, 2H; NH),
Compound31 : A solution of NaOH (6.00 g, 0.15 mmol) in water (40 mL)
was added dropwise to a solution of compound 28 (1.55 g, 2.00 mmol) in
THF (60.00 mL). The mixture was stirred for 24 h at 808C and the pH of
the solution was adjusted to 9 by the addition of conc. HCl. The solvent
was evaporated and the residue was dissolved in CHCl3 (200 mL) and
water (200 mL). The two layers were separated and the organiclayer was
extracted with HCl (200 mL). The organic layer was dried with Na2SO4
and the solvent was evaporated. The crude product was purified by
column chromatography (SiO2, gradient CH2Cl2 ! CH2Cl2/EtOAc10:1
! EtOAc). Yield: 1.40 g (92%) as a white solid; 1H NMR (400 MHz,
CDCl3): d=5.01 (s, 4H; CH2Bn), 5.02 (s, 8H; CH2Bn), 6.55 (t, 4J=
2.2 Hz, 2H; Ph), 6.66 (d, 4J=2.2 Hz, 4H; Ph), 6.80 (t, 4J=2.3 Hz, 1H;
Ph), 7.14 (d, 4J=2.3 Hz, 2H; Ph), 7.31 (m, 20H; Ph), 12.79 ppm (brm,
1H; COOH); 13C NMR (100.6 MHz, CDCl3): d=69.2 (CH2Bn), 100.9,
106.1, 106.2, 107.9, 127.3, 127.5, 128.1, 132.7, 136.6, 138.8, 159.1, 159.4
(Ph), 166.8 ppm (C=O); IR (ATR): nmax =3235, 3065, 3030, 2910, 2868,
1691, 1594, 1444, 1366, 1305, 1162, 1042, 845, 818, 753, 733, 695 cmꢀ1; MS
(FAB): m/z (%): 759 [M]+; elemental analysis calcd (%) for C49H42O8
(758.85): C 77.55, H 5.58; found: C 77.46, H 5.58.
ꢀ
ꢀ
5.05 (m, 8H; CH2 Bn), 5.20 (m, 8H; CH2 Bn), 5.74 (m, 10H; *CH),
5.89 (m, 4H; *CH), 6.61 (brm, 4H; NH), 7.09 (m, 12H; Ph), 7.14 (m,
8H; Bn), 7.27 (m, 20H; Bn), 7.38 (m, 14H; Bz), 7.53 (m, 7H; Bz), 7.91
(m, 8H; Bz), 8.01 (m, 6H; Bz), 9.53 ppm (s, 2H; NH); 13C NMR
(100.6 MHz, CDCl3): d=23.8, 24.7, 25.3, 25.5, 25.7, 26.8,28.7, 28.8 (CH2),
33.0, 33.2, 33.3, 33.7 (CH2COO), 38.8, 39.0, 39.2, 41.0 (CH2N), 67.7, 67.9
(CH2Bn), 70.7, 71.1, 71.2, 72.3, 72.9, 73.1 (*CH), 128.4, 128.5, 128.6,
128.7, 128.8, 129.0, 130.2, 133.8, 134.0, 134.2, 134.6, 134.9, (Ph), 148.2,
149.4, 165.31, 165.33, 165.36, 165.9, 166.0, 166.5, 166.6, 166.7, 172.0, 172.5,
172.6 ppm (C=O); IR (ATR): nmax =3250, 2941, 2343, 1735, 1687, 1540,
1458, 1254, 1213, 1197, 1125, 959, 714 cmꢀ1; MS (FAB): m/z (%): 3297
[M]+; UV/Vis (CH3OH): l (e)=264 (8000), 232 nm (82000); elemental
analysis calcd (%) for C178H183N9O53·CH2Cl2: C 63.58, H 5.51, N 3.73;
found: C 63.59, H 5.58, N 3.71; [a]2D0 =+26 (c=0.200, CH2Cl2).
Compound28 : The reaction was performed under nitrogen atmosphere.
A mixture of compound 25 (4.89 g, 13.00 mmol), methyl-3,5-dihydroxy-
benzoate (1.09 g, 6.50 mmol), K2CO3 (2,25 g, 16.30 mmol) and [18]crown-
6 (0.35 g, 1.30 mmol) was suspended in dry acetone (70 mL) and refluxed
for 24 h. Water (100 mL) and Et2O (100 mL) were added to the solution
and the layers were separated. The water layer was extracted with Et2O
Compound32
: A solution of NaOH (12.00 g, 0.3 mmol) in water
(100 mL) was added dropwise to a solution of compound 29 (3.50 g,
2.16 mmol) in THF (60.00 mL). The mixture was stirred for 24 h at 808C.
The obtained two layers were separated and the water layer was extract-
ed with CHCl3 (3x 100 mL). The organiclayer was extracted with HCl
(100 mL).and dried over Na2SO4. The solvent was evaporated and the
crude mixture purified by column chromatography (SiO2, EtOAc/CH2Cl2
1:20). Yield: 2.70 g (78%) as a white solid; 1H NMR (400 MHz, CDCl3):
d=4.95 (s, 8H; CH2Bn), 4.97 (s, 4H; CH2Bn), 4.99 (s, 16H; CH2Bn),
6.54 (t, 4J=2.4 Hz, 2H; Ph), 6.55 (t, 4J=2.1 Hz, 4H; Ph), 6.66 (d, 4J=
2.2 Hz, 12H; Ph), 6.82 (t, 4J=2.2 Hz, 1H; Ph), 7.27 (d, 4J=3.0 Hz, 2H;
Ph), 7.34 (m, 40H; Ph), 11.59 ppm (brm, 1H; COOH); 13C NMR
(100.6 MHz, CDCl3): d=70.0, 70.1, 70.2 (CH2Bn), 101.5, 101.7, 106.3,
106.4, 107.9, 108.9, 127.4, 127.9, 128.4, 130.9, 136.6, 138.6, 139.0, 159.5,
159.9, 160.0 (Ph), 170.4 ppm (C=O); IR (ATR): nmax =3065, 3030, 2872,
(3”150 mL) and the organiclayer was dried over Na SO4. After evapora-
2
tion of the solvent the crude product was purified by column chromatog-
raphy (SiO2, CH2Cl2). Yield: 1.63 g (33%) as a white solid; 1H NMR
(400 MHz, CDCl3): d=3.83 (s, 3H; CH3), 4.92 (s, 4H; CH2Bn), 4.95 (s,
8H; CH2Bn), 6.50 (t, 4J=2.2 Hz, 2H; Ph), 6.60 (d, 4J=2.3 Hz, 4H; Ph),
6.70 (t, 4J=2.3 Hz, 1H; Ph), 7.20 (d, 4J=2.3 Hz, 2H; Ph), 7.29 ppm (m,
20H; Ph); 13C NMR (100.6 MHz, CDCl3): d=52.7 (CH3), 70.5 (CH2Bn),
102.1, 106.8, 107.6, 108.9, 128.0, 128.4, 129.0, 132.5, 137.1, 139.3, 160.1,
160.6 (Ph), 167.1 ppm (C=O); IR (ATR): nmax =3246, 3030, 2953, 2876,
1714, 1594, 1440, 1374, 1336, 1305, 1243, 1162, 1058, 1031, 834, 726,
695 cmꢀ1; MS (FAB): m/z (%): 773 [M]+; elemental analysis calcd (%)
for C50H44O8: C 77.70, H 5.74; found: C 76.40, H 5.54.
Compound29 : The reaction was performed under a nitrogen atmos-
phere. A mixture of compound 26 (5.24 g, 6.49 mmol), methyl-3,5-dihy-
droxybenzoate (0.55 g, 3.24 mmol), K2CO3 (2.24 g, 16.21 mmol) and
[18]crown-6 (0.35 g, 1.30 mmol) was suspended in dry acetone (120 mL)
and refluxed for 24 h. Water (40 mL) and Et2O (60 mL) were added to
the solution and the layers were separated. The water layer was extracted
with Et2O (3”150 mL) and the organiclayer was dried over Na 2SO4.
After evaporation of the solvent the crude product was purified by
column chromatography (SiO2, CH2Cl2). Yield: 3.73 g (71%) as a white
solid; 1H NMR (400 MHz, CDCl3): d=3.83 (s, 3H; CH3), 4.95 (s, 8H;
1691, 1594, 1444, 1370, 1328, 1305, 1162, 1042, 822, 733, 695, 681 cmꢀ1
MS (FAB): m/z (%): 1608 [M]+; elemental analysis calcd (%) for
100H90O16 (1607.83): C 78.44, H 5.64; found: C 77.20, H 5.98.
;
C
General procedure for the preparation of compounds 3a–c: The reaction
was performed under nitrogen atmosphere. The carboxylic acid
(1.5 mmol), DMAP (1.5 mmol) and HOBt (1.5 mmol) were added to a
solution of the alcohol (1.5 mmol) in DMF (40 mL). A solution of DCC
(1.5 mmol) in DMF (3 mL) was added slowly at room temperature and
the mixture was stirred for 72 h. The solvent was evaporated and the re-
maining residue was dissolved in EtOAc (10 mL). The precipitate collect-
ed over night was filtered and the solvent evaporated. The crude mixture
was further purified by column chromatography.
4
CH2Bn), 4.97 (s, 4H; CH2Bn), 5.00 (s, 16H), 6.53 (t, J=2.3 Hz, 2H; Ph),
6.55 (t, 4J=2.2 Hz, 4H; Ph), 6.65 (d, 4J=2.2 Hz, 4H; Ph), 6.66 (d, 4J=
2.3 Hz, 8H; Ph), 6.78 (t, 4J=2.4 Hz, 1H; Ph), 7.38 ppm (m, 42H; Ph);
13C NMR (100.6 MHz, CDCl3): d=52.3 (CH3), 70.0, 70.1 (CH2Bn),
101.54, 101.61, 106.3, 106.4, 107.6, 108.3, 127.4, 127.8, 128.4, 132.0, 137.1,
Compound3a : Compound 3a was synthesized according to the general
procedure from dendron 30 (501 mg, 1.5 mmol) and compound 22
(344 mg, 1.5 mmol). The crude product was purified by column chroma-
tography (SiO2, gradient CH2Cl2 ! CH2Cl2/EtOAc, 2:8). Yield: 279 mg
(34%) as a white solid; 1H NMR (400 MHz, [D6]DMSO): d=1.34 (m,
4H; CH2), 1.51 (m, 2H; CH2), 1.66 (m, 2H; CH2), 3.64 (t, 3J=7.1 Hz,
2H; CH2), 4.23 ((t, 3J=6.5 Hz, 2H; CH2), 5.15 (s, 4H; CH2Bn), 6.96 (s,
1H; Ph), 7.14 (s, 2H; Ph), 7.39 (m, 10H; Ph), 11.52 ppm (brm, 2H; NH);
13C NMR (100.6 MHz, [D6]DMSO): d=26.0, 26.6, 28.1, 28.9, 41.2, 65.7-
(CH2), 70.4(CH2Bn), 107.7, 108.7, 128.6, 128.9, 129.3, 132.7, 137.5 (Ph),
149.5, 150.7(C=O), 160.4 (Ph), 166.2 ppm (C=O); IR (ATR): nmax =3204,
3096, 1733, 1710, 1602, 1459, 1401, 1355, 1305, 1243, 1212, 1173, 1054,
760, 733 cmꢀ1; MS (FAB): m/z (%): 545 [M]+; elemental analysis calcd
(%) for C30H31N3O7 (545.58): C 66.04, H 5.73, N 7.70; found: C 65.94, H
5.91, N 7.52.
138.7, 139.0, 159.5, 160.1, 160.2 (Ph), 166.5 ppm (C=O); IR (ATR): nmax
=
3062, 3030, 2927, 2876, 1714, 1594, 1497, 1440, 1374, 1343, 1321, 1297,
1153, 1042, 834, 735, 695, 631 cmꢀ1; MS (FAB): m/z (%): 1622 [M]+; ele-
mental analysis calcd (%) for C106H92O16: C 78.50, H 5.72; found: C
78.13, H 5.69.
Compound30 : A mixture of NaOH (24.00 g, 0.60 mol) and compound 27
(10.00 g, 28.70 mmol) was suspended in water (200 mL) and stirred for
24 h at 708C. After evaporation of the solvent the residue was dissolved
in EtOAc(80 mL) and filtrated. The solvent was evaporated and the
product was dried in vacuum. Yield: 9.16 g (95%) as a white solid; 1H
4
NMR (400 MHz, [D6]DMSO): d=5.19 (brm, s, 4H; CH2Bn) 6.97 (t, J=
2.3 Hz, 1H; Ph), 7.21 (d, 4J=2.3 Hz, 2H; Ph), 7.44 (m, 10H; Ph),
13.39 ppm (brm, s, 1H; COOH); 13C NMR (100.6 MHz, [D6]DMSO):
Chem. Eur. J. 2006, 12, 2663 – 2679
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2677

A. Hirsch et al.
Compound3b : Compound 3b was synthesized according to the general
procedure from dendron 31 (1.14 g, 1.5 mmol) and compound 22
(344 mg, 1.5 mmol). The crude product was purified by column chroma-
tography (SiO2, gradient CH2Cl2 ! CH2Cl2/EtOAc, 6:4). Yield: 0.43 g
(30%) as a pale yellow solid; 1H NMR (400 MHz, [D6]DMSO): d=1.32
683 cmꢀ1; elemental analysis calcd (%) for C9H15N3O4 (229.23): C 47.16,
H 6.60, N 18.33; found: C 45.95, H 6.23, N 17.54.
Compound33 : 3,4-Diethoxy-5-propoxybenzoicacid (204 mg, 0.80 mmol)
was dissolved in CH2Cl2 (50 mL) and cooled to 08C. DMAP (108 mg,
0.80 mmol), HOBt (98 mg, 0.80 mmol) and EDC·HCl (154 mg,
0.80 mmol) was added and the reaction was stirred for one hour at 08C.
After the addition of 5-amino-N,N’-bis[6-(3,3-dimethylbutyrylamino)pyri-
dine-2-yl]isophtalamide[21] (150 mg, 0.27 mmol) the mixture was stirred
for 48 h at room temperature. The crude product was purified by column
chromatography (SiO2, CH2Cl2/MeOH, 30:1). Yield: 90 mg (42%) as a
pale yellow solid; m.p. 134 C; 1H NMR (400 MHz, [D6]DMSO): d=1.01
3
(m, 4H; CH2), 1.50 (m, 2H; CH2), 1.67 (m, 2H; CH2), 3.60 (t, J=7.3 Hz,
3
2H; CH2), 4.22 ((t, J=6.6 Hz, 2H; CH2), 5.06 (brm, 12H; CH2Bn), 6.62
4
4
(d, J=2.2 Hz, 2H; Ph), 6.70 (d, 4J=2.1 Hz, 4H; Ph), 6.92 (t, J=2.2 Hz,
1H; Ph), 7.13 (s, 2H; Ph), 7.37 (m, 20H; Ph), 11.38 ppm (brm, 2H; NH);
13C NMR (100.6 MHz, [D6]DMSO): d=25.0, 25.7, 27.2, 28.0, 40.1, 64.7-
(CH2), 69.34(CH2Bn), 101.2, 106.4, 106.8, 107.9, 127.7, 127.8, 128.4, 131.8,
136.9, 139.1 (Ph), 148.6, 149.8 (C=O), 159.3, 159.6 (Ph), 165.3 ppm (C=
O); IR (ATR): nmax =3235, 3069, 2937, 2860, 1718, 1687, 1594, 1451, 1374,
1301, 1239, 1150, 1046, 834, 753, 699 cmꢀ1; MS (FAB): m/z (%): 970
[M]+; elemental analysis calcd (%) for C58H55N3O11 (970.07): C 71.81, H
5.71, N 4.33; found: C 71.33, H 5.91, N 4.13.
3
3
(s, 18H, C(CH3)3), 1.25 (t, J=7.2 Hz, 3H; CH3), 1.36 (t, J=7.0 Hz, 6H;
CH3), 2.29 (s, 4H; CH2), 4.04 (m, 2H; CH2O), 4.12 (m, 4H; CH2O), 7.32
( s, 2H; Ph) 7.81 (m, 6H; Py), 8.28 (s, 1H; Ph), 8.55(s, 2H; Ph), 10.02 (s,
2H; CONH), 10.42 (s, 2H; CONH), 10.44 (s, 1H; CONH); 13C NMR
(100.6 MHz, [D6]DMSO): d=14.7, 15.5 (CH3), 29.6 (C(CH3)3), 30.1
(CH2), 49.3 (C), 64.3, 68.1 (CH2O), 106.3, 110.0, 110.4, 122.1, 123.2, 128.9,
134.7, 136.1, 139.7, 140.1, 140.2, 150.1, 150.6, 152.3 (Ph, Py), 165.1, 165.2,
170.9 ppm (C=O); IR (ATR): nmax =3277, 2957, 2343, 1671, 1583, 1502,
1444, 1328, 1297, 1227, 1123, 1027, 799, 753 cmꢀ1; MS (FAB): m/z (%):
797 [M]+; elemental analysis calcd (%) for C43H53N7O8 (795.92): C 64.69,
H 6.71, N 12.32; found: C 64.95, H 6.63, N 12.54.
Compound3c : Compound 3c was synthesized according to the general
procedure from dendron 32 (1.14 g, 1.5 mmol) and compound 22
(344 mg, 1.5 mmol). The crude product was purified by column chroma-
tography (SiO2, gradient CH2Cl2 ! CH2Cl2/EtOAc, 6:4). Yield: 552 mg
(46%) as a white solid; 1H NMR (400 MHz, [D6]DMSO): d=1.24 (m,
2H; CH2), 1.31 (m, 2H; CH2), 1.48 (m, 2H; CH2), 1.63 (m, 2H; CH2),
3
3
3.59 (t, J=7.3 Hz, 2H; CH2), 4.18 ((t, J=6.5 Hz, 2H; CH2), 4.99 (s, 8H;
4
4
CH2Bn), 5.04 (s, 20H; CH2Bn), 6.60 (t, J=2.1 Hz, 6H; Ph), 6.67 (d, J=
2.1 Hz, 8H; Ph), 6.68 (d, 4J=2.1 Hz, 4H; Ph), 6.94 (t, 4J=2.1 Hz, 1H;
Ph), 7.14 (d, 4J=2.0 Hz, 2H; Ph), 7.34 (m, 40H, Ph), 11.38 ppm (brm,
2H; NH); 13C NMR (100.6 MHz; [D6]DMSO): d=25.0; 25.7; 27.2; 28.0;
40.1; 64.7(CH2); 69.34(CH2Bn); 107.7; 108.7; 128.6; 128.9; 129.3; 132.7;
137.5 (Ph); 149.5; 150.7(C=O); 160.4 (Ph); 166.2 ppm (C=O); IR (ATR):
nmax =3235; 3088; 3065; 3034; 2934; 2868; 1698; 1594; 1447; 1374; 1297;
1146; 1042; 830; 733; 695 cmꢀ1; MS (FAB): m/z (%): 1816 [M]+; elemen-
tal analysis calcd (%) for C114H103N3O19 (1819.05): C 75.27; H 5.71; N
2.31; found: C 73.82; H 5.72; N 2.25.
Acknowledgements
This work was supported by Deutsche Forschungsgemeinschaft (SFB
583: Redoxaktive Metallkomplexe - Reaktivitätssteuerung durch moleku-
lare Architekturen). We thank E. W. Meijer and R. Sijbesma for critical
and thoughtful discussions on the problem of structural perfection of
self-assembled supramolecular dendrimers. We thank F. Würthner from
the university of Würzburg for providing access to the CD spectrometer.
1-(6-Hydroxyhexyl)-biuret (21): 1-Nitrobiuret (4.44 g; 30.0 mmol) was
dissolved in water (45 mL) and 6-aminohexanol (3.63 g; 30.0 mmol) was
added. The mixture was stirred for one hour and then heated at reflux
for 1 h. The solution was cooled one ice and filtered to remove a small
amount of insoluble material before being concentrated to give the crude
product. The product was purified by recrystalization from ethanol.
Yield: 2.46 g (40%) as a white solid; 1H NMR (400 MHz; [D6]DMSO):
d=1.27 (m; 4H; CH2); 1.34 (m; 4H; CH2); 3.06 (dt; 3J1 =6.7 Hz/3J2 =
6.0 Hz; 2H, CH2OH), 3.37 (dt, 3J1 =11.8 Hz/3J2=5.6 Hz, 2H, CH2NH),
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3
4.33 (t, J=5.2 Hz, 1H, OH), 6.72 (brm, 2H, NH2), 7.46 (brm, 1H, NH),
8.50 ppm (brm, 1H, NH); 13C NMR (100.6 MHz, [D6]DMSO): d=25.5,
26.5, 29.7, 32.8 (CH2), 39.0 (CH2NH), 60.9 (CH2OH), 154.7, 155.8 ppm
(C=O); IR (ATR): nmax =3397, 3354, 3296, 2941, 2864, 1733, 1675, 1586,
1540, 1482, 1413, 1285, 1247, 1216, 1139, 1065, 1007, 984, 811, 764, 729,
633 cmꢀ1; elemental analysis calcd (%) for C8H17N3O3 (203.24): C 47.28,
H 8.43, N 20.67; found: C 47.13, H 8.65, N 20.77.
1-(6-Hydroxyhexyl)-[1,3,5]-triazin-2,4,6-trion (22): The reaction was per-
formed under nitrogen atmosphere. A solution of sodium ethoxide was
prepared from sodium metal (517 mg, 22.50 mmol) and absolute ethanol
(20 mL). Diethyl carbonate 1.82 mL, 15.0 mmol) was added with stirring
followed by 1-(6-hydroxyhexyl)-biuret (21) (1.52 g, 7.50 mmol). The mix-
ture was heated at reflux for 2 h, during which the sodium salt of the
product precipitated from solution. The mixture was allowed to cool to
room temperature, filtered and the precipitate was washed with cold
ether/ethanol 1:1. The residue was dissolved in the minimum volume of
water and the solution was carefully neutralized with 1m sulfuricaicd.
The white product was filtered and dried in vacuum. Yield: 0.93 g (54%)
as a white solid; 1H NMR (400 MHz, [D6]DMSO): d=1.25 (m, 4H,
CH2), 1.43 (m, 2H; CH2), 1.51 (m, 2H; CH2), 3.35 (t, 3J=6.2 Hz, 2H;
CH2N), 3.60 (t, 3J=7.3 Hz, 2H; CH2OH), 4.32 (brm, 1H; OH),
11.63 ppm (brm, 2H; NH); 13C NMR (100.6 MHz, [D6]DMSO): d=25.2,
26.0, 27.4, 32.4 (CH2), 40.3 (CH2N), 60.59 (CH2OH), 148.6, 149.8 ppm
(C=O); IR (ATR): nmax =3393, 3204, 3088, 2941, 2864, 1745, 1725, 1679,
1459, 1417, 1363, 1208, 1170, 1058, 1031, 1011, 914, 822, 791, 757,
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www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 2663 – 2679

Self-Assembled Dendrimers
FULL PAPER
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Received: October 20, 2005
Published online: February 21, 2006
Chem. Eur. J. 2006, 12, 2663 – 2679
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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