Synthesis and chiroptical properties of a new type of chiral depsipeptide dendrons

Article abstract of DOI:10.1016/S0040-4020(03)00459-9

A new type of chiral depsipeptide dendrons based on tartaric acid as branching juncture and ω-aminocapronic acid as spacer has been prepared. Natural and unnatural tartaric acid building blocks have been incorporated, providing access to combinatorial libraries. All compounds have been completely characterized by FAB-MS, EA analysis, ¹H/¹³C NMR- and UV/Vis-spectroscopy. ¹H NMR relaxation measurements have been used to examine the conformational flexibility of these dendrons in CH₃CN and CH₃OH and indicate a less flexible structure in CH₃CN. Pulse gradient spin echo (PGSE) NMR measurements correlate these findings to molecular dimensions. A reduced size for the dendrons in CH₃CN compared to CH₃OH leads to the assumption of a more compact structure in this solvent. Additional polarimetric data reveal, that observed changes in optical activity with increasing generation can in CH₃OH be explained by constitutional effects of the dendron structure but not in CH₃CN. CD measurements are in agreement with these findings and show a linear increase of the Cotton effects with increasing generation for CH₃OH but not for CH₃CN. It can be concluded that the conformation within the dendrons is very sensitive to environmental conditions and that a chiral secondary structure might be stabilized in CH₃CN. Initial studies revealed that chirality transfer to the focal functionality occurs.

Full text of DOI:10.1016/S0040-4020(03)00459-9

Tetrahedron 59 (2003) 3899–3915
Synthesis and chiroptical properties of a new type
of chiral depsipeptide dendrons
*
Boris Buschhaus, Walter Bauer and Andreas Hirsch
¨ ¨ ¨
Institut fur Organische Chemie, Friedrich Alexander Universitat Erlangen-Nurnberg, Henkestr. 42, D-91054 Erlangen, Germany
Received 31 October 2002; revised 16 December 2002; accepted 10 January 2003
Abstract—A new type of chiral depsipeptide dendrons based on tartaric acid as branching juncture and v-aminocapronic acid as spacer has
been prepared. Natural and unnatural tartaric acid building blocks have been incorporated, providing access to combinatorial libraries. All
1
1
compounds have been completely characterized by FAB-MS, EA analysis, H/13C NMR- and UV/Vis-spectroscopy. H NMR relaxation
measurements have been used to examine the conformational flexibility of these dendrons in CH3CN and CH3OH and indicate a less flexible
structure in CH3CN. Pulse gradient spin echo (PGSE) NMR measurements correlate these findings to molecular dimensions. A reduced size
for the dendrons in CH3CN compared to CH3OH leads to the assumption of a more compact structure in this solvent. Additional polarimetric
data reveal, that observed changes in optical activity with increasing generation can in CH3OH be explained by constitutional effects of the
dendron structure but not in CH3CN. CD measurements are in agreement with these findings and show a linear increase of the Cotton effects
with increasing generation for CH3OH but not for CH3CN. It can be concluded that the conformation within the dendrons is very sensitive to
environmental conditions and that a chiral secondary structure might be stabilized in CH3CN. Initial studies revealed that chirality transfer to
the focal functionality occurs. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
ascertained in a system by Parquette.7 It is described how
intramolecular hydrogen-bonding, solvophobic com-
pression and non-covalent packing interactions result in a
helical conformation. However, most systems consisting
of chiral branching units could not assign for certain a
secondary structure or suggest a lack of conformational
order.8
Chirality is a characteristic property of biopolymers such as
proteins and DNA in nature and is crucial in the interplay
between structure and function.1 Originating from small
chiral monomers it is often expressed in an asymmetric
superstructure, for example, a helix. Noncovalent inter-
actions result in a folding process that produces distinctive
three-dimensional environments.2 Only the correctly
assembled globular structure enables the macromolecules
to fulfill their various functions e.g. chiral recognition,
enantioselective catalysis, clathration and transport of small
molecules. An important goal in mimicking biology is
therefore to delineate the factors which govern macro-
molecular asymmetry. Dendrimers3 can be considered as
model compounds for natural macromolecules because of
their well-defined, highly ordered and globular structure.
Furthermore, incorporating chiral units should open the
possibility to study the effect of chirality in macromolecular
systems.4,5 Chiral dendrimers bear the potential to build up
a more or less rigid asymmetric shape with a chiral surface
and chiral cavities. The expression of chirality in the form of
a secondary conformational order would then be observable
by chiroptical methods.6 In the studies reported so far the
presence of a secondary structure could be unambiguously
Recently, we introduced the concept of chiral depsipeptide
dendrimers.8h This new class of dendrimers closely
resembles the structure of natural depsipeptides which
consist of a-hydroxy and a-amino acids, connected by ester
and amide linkages.9 As branching units, tartaric acid
derivatives were chosen, and as spacer, various di- and
tripeptides were attached. In the synthetic sequence,
C-protected amino acids or peptides were coupled by
amide formation reactions to tartaric acid derivatives with
one unprotected carboxylic group. The synthesis of higher
generation dendrimers was carried out by a repetitive
C-deprotection of the peptides and a subsequent coupling
with the deprotected hydroxy groups of the tartaric acid
derivatives. However, because of the complex synthesis and
demanding purification processes only small amounts of
third generation dendrimers could be made accessible.8h
Therefore the deduction of the chiroptical properties of the
dendrons and their use as peptide mimetic building blocks in
synthesis was limited.
Keywords: depsipeptide dendrimers; dendrimer conformation; solvent
dependant folding; pulse gradient spin echo (PGSE) measurements;
circular dichroism.
Now we report on a different concept for the synthesis of
depsipeptide dendrons based on tartaric acid as branching
juncture and v-aminocapronic acid as spacer. Compared to
*
Corresponding author. Fax: þ49-9131-8526864;
e-mail: andreas.hirsch@organik.uni-erlangen.de
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00459-9

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B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
Scheme 1. (a) pTSA, 1078C, benzene; (b) DMAP, HOBt, DCC, CH2Cl2; (c) DCC, HOBt, CH2Cl2.
the previous concept the overall synthetic sequence could be
shortened by circumventing the multi-step synthesis of the
peptide spacer. Furthermore the reactivity of the branching
juncture was reversed and now the repetitive units are
connected by amide instead of ester bond formation, which
results in higher yields for the coupling steps. Most of the
chiral dendrimers reported so far consist of only one
enantiomeric form of the chiral building blocks. Here we
incorporated both the natural and unnatural tartaric acid,
providing access to libraries of various enantiomers and
diastereomers. The chiroptical properties are reported in
regard to solvent conditions. Furthermore, in an initial
attempt, the use of the dendrons as chiral micro-
environments is demonstrated by attaching anthracene
chromophores to the focal functionality.
Altogether, the yield of the first generation dendrons 7 and
8 was ,27% based on the tartaric acids 1 and 2,
respectively. Furthermore, in all these steps no chromato-
graphic separation process was necessary.
For the growth of the dendritic branches the amino functions
of 7 and 8 were deprotected with trifluoroacetic acid
(Scheme 2).11 After the removal of the solvent, 9 and 10
were obtained as TFA adducts in 99% yield. Deprotection of
the carboxylic groups was carried out by stirring 7 and 8
with 10% Pd/C in MeOH in an H2-atmosphere for 24 h.
After filtration of the catalyst and removal of the solvent, 11
and 12 were obtained in 99% yield. No further purification
was required. Reaction of the diacids 11 and 12 with the
amines 9 and 10 under typical peptide coupling conditions
(DCC, HOBt, 08C)11 afforded the enantiomers 13, 14 and
the diastereomer 15 in 25 and 45% yield, respectively
(Scheme 2). Note that the outer shell of 15 is similar to 13
but the inner layer is enantiomeric to 14.
2. Results and discussion
2.1. Synthesis of the depsipeptide dendrons
Repetition of this reaction cycle, including deprotection of
13, 14, 15 and coupling with 11 or 12 gave third generation
dendrons 19, 20 and 21 (Scheme 3). The same reaction
conditions led to a yield of 16% for the enantiomeric
compounds 19 and 20, and to 71% yield for the
diastereomer 21 in all attempts. The different yields are
surprising if it is considered that the configurational
difference for example between 15 and 13 is located at a
distance of 9 atoms and 10 bonds. However, a similar
observation was made by Seebach.12 Here the effect was
even more pronounced, since in their synthetic sequence
some diastereomers would not form at all. A further
coupling after deprotection of these dendrons did not
occur. Instead, only the corresponding fourth generation
monoamides have been isolated. Thus, for the successful
The synthesis of the key building blocks is depicted in
Scheme 1. First generation dendrons 7 and 8 were
synthesized using a Steglich coupling10 of tartaric acid
derivatives 5 and 6, and BOC-protected v-aminocapronic
acid. To prevent the rearrangement of activated v-BOC-
aminocapronic acid10 the use of HOBt was essential.
Considering that it is an early step in dendron synthesis,
the yields of 70–75% are satisfactory. A simple purification
method allowed the facile preparation of 7 and 8 on a 30 g
scale. The tartaric acid derivatives 5 and 6 were obtained by
protecting the carboxylic groups of natural and unnatural
tartaric acid 1 and 2 with benzylic alcohol in 92% yield,
followed by protection of one hydroxy group of 3 and 4 by
benzoic acid in a statistical reaction (38% yield).

B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
3901
Scheme 2. (a) TFA, CH2Cl2; (b) H2, Pd/C, CH3OH; (c) DCC, HOBt, NEt3, CH2Cl2.
preparation of higher generation branches an elongation of
the diacids 11 and 12 might be necessary to reduce steric
congestion.
remarkable (19, 20 Rf¼0.15, 21 Rf¼0.08; CH2Cl2/MeOH
25:1; silica gel).
2.2. Characterization
All dendrons were isolated as colorless solids. They are
highly soluble in unpolar and polar aprotic solvents such as
CH2Cl2, CH3CN and toluene and they are readily soluble in
polar protic solvents such as CH3OH, EtOH. The Rf values
of the second generation dendrons 13–15 (EtAc/hex 1:1;
silica gel) did not show large differences (13, 14 Rf¼0.33;
15 Rf¼0.34). However, in the third generation dendrons the
differences between the diastereomers 19–21 become
All dendrons were characterized by 1H and 13C NMR, UV,
mass spectrometry, elemental analysis, and by their specific
and molar optical rotations [a]D and [f]D. FAB mass
spectroscopy confirmed the expected molecular weights and
revealed the purity of the samples. Typically, the base peak
corresponds to [M2BOC]þ, whereas [MþH]þ is small but
noticeable.

3902
B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
O
O
O
O
O
N
H
O
O
O
O
O
O
O
O
NH
O
O
O
O
O
O
O
O
H
O
H
N
O
O
N
O
O
O
O
O
O
O
O
O
O
N
N
O
O
O
O
O
H
H
O
O
13, 14, 15
a)
O
16, 17, 18 (99%)
O
O
O
O
O
O
O
H
N
b)
O
O
O
R,R
S,S
R,R
R,R
S,S
S,S
S,S
S,S
R,R
R,R
S,S
S,S
R,R
R,R
R,R
S,S
R,R
R,R
R,R
S,S
R,R
19 (18%)
Scheme 3. (a) TFA, CH2Cl2; (b) 11, 12, DCC, HOBt, NEt3, CH2Cl2.
20 (17%)
21 (71%)
2.2.1. 1H/13C NMR spectroscopy. A characteristic feature
of these chiral systems is that all C- and H- atoms are
topologically different even if they originate from identical
layers in the dendron. This is reflected by the splitting of the
signals throughout all NMR-spectra. In the 1H NMR spectra
of the third generation dendron 20 (recorded in CD3CN,
Fig. 1C) the signals of the aromatic protons are located in
the range between d¼7.0–8.3, while the signals of the alkyl
and BOC protons are located between d¼1.0–3.4. The
singlet of the t-butyl protons of the BOC-group appears at
d¼1.38. The alkyl protons next to the ester group linkages
resonate at d¼2.2 as well resolved multiplets, whereas the
protons in close vicinity to the amide groups lead to broad
multiplets at d¼3.16. Characteristic are the regions between
d¼5.0–5.4 and d¼5.5–6.0, where the resonances of the
peripheral benzylic CH2-groups and the CH-protons of the
tartaric acid units are localized (Fig. 1C). Two different sets
of N–H signals are found. The signal at d¼5.35 is attributed
to the amide proton of the BOC-group and the set of signals
at d¼6.9 is assigned to the remaining N–H protons. In the
aromatic region the ortho protons of the benzyloxy groups
experience strong deshielding and are located at d¼7.8 and
d¼8.1. The gradual change of the dendritic microenviron-
ment on going from outside to inside along the three layers
leads to a gradual downfield shift of the H nuclei. The
1
protons of the different layers of the tartaric acid units were
assigned by integration and give rise to distinct sets of
signals over a broad range of ,0.5 ppm (Fig. 1C and
Scheme 3, first layer depicted in green, second layer
depicted in blue, third layer depicted in red). The same is
true for the protons in close vicinity to the amid groups
(,0.1 ppm) (d¼3.10–3.20). Even more pronounced is the
effect for the ortho nuclei of the aromatic benzyloxy groups
(,0.1–0.25 ppm) (d¼7.8–8.1). The corresponding shifts
1
of other H nuclei which are located in the interior of the
dendron could not be determined exactly due to close signal
overlapping. Similar observations are reported by Seebach13
in 1H/19F NMR spectra and by 1H NMR studies of
Stoddart14 and Meijer.15 No significant differences in
chemical shifts between the pairs of enantiomers and the
corresponding diastereomer throughout all generations
have been observed for the same groups of 1H-nuclei.
Furthermore, no line broadening was observed in CD3CN
for all stereoisomers up to second generation and for 19

B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
3903
CD3CN and CD3OD, respectively. The measurements were
performed using the standard inversion-recovery method.16
In Figure 2 the T1 relaxation times are plotted as a function
of the position of the tartaric acid units in the dendron. For
CD3OD the relaxation times remain independent of the
position of the unit throughout the whole dendron, whereas
in CD3CN the relaxation times decrease by going to the
outer layer. Therefore the segmental mobility decreases in
CD3CN on going to the periphery.17 To the contrary, the
segmental mobility is independent of the position of the unit
in the dendron in CD3OD. Referring to the conformations in
solution, it can therefore be assumed, that the structure of
the dendron is less flexible in CD3CN, with the various
layers influencing each other. In CD3OD the conformational
flexibility is more pronounced.
2.2.3. PGSE NMR Experiments. Pulsed-field gradient
nuclear magnetic resonance (PGSE) provides a powerful
tool for measuring translational motion in solution. The
method relates the attenuation of the echo signal from a
Hahn spin-echo pulse sequence containing a magnetic field
gradient pulse in each t period to the adjournment of the
observed spins and therefore the related molecules. The
signal intensities are hence connected to diffusion rates and
allow the resolution of molecular extensions.18 In our case,
PGSE NMR is used to further analyse conformational
ordering within the dendrons. If the conformation of the
dendrons is more compressed and folded in CD3CN
compared to CD3OD this should be clearly seen in the
observed molecular dimensions. Diffusion coefficients are
experimentally determined by observing the decay of the
signal intensity as a function of increasing gradient strength.
The decrease depends on the diffusion rates of the spin-
labelled molecules. For sine gradient pulses the following
Stejskal–Tanner equation is applied:18b
Figure 1. 1H NMR spectra of 20 in CDCl3 (A), CD3OD (B) and CD3CN (C)
at room temperature (section of the CH-protons of the tartaric acid building
blocks). first layer depicted in green, second layer depicted in blue, third
layer depicted in red.
and 20 even up to third generation. However, a small line
broadening effect was detectable for third generation
dendron 21.
To study the interaction of these dendrons with the solvent
and the effects of the solvent on the conformation of the
dendrons we recorded 1H NMR spectra in DMSO-d6,
CDCl3, CD3CN and CD3OD. Even though the characteristic
regions of the resonances remain roughly unchanged, the
signal splitting differs significantly (Fig. 1). However, based
only on these investigations it cannot be decided whether
this is due to a normal solvent shift or due to an adaption of
different conformations. As a consequence we carried out
detailed NMR investigations.
Esin
¼
ꢀ
ꢂ
ꢀ
ꢁ
ꢀ
ꢁ
ꢃ
ꢁ
Np
Np
exp 2g2g2Dd2 cos2
3d þ sin2
ð4D 2 dÞ =ðNpÞ
2
2
2
ð1Þ
2.2.2. T1 relaxation times. To study the segmental mobility
of the distinct layers in the dendron with regard to the
solvent, we determined the spin-lattice relaxation times (T1)
of the tartaric acid units in the aprotic and protic solvents
Figure 3. Stacked plot 1H NMR spectra of dendron 20 in DMSO-d6
acquired with increasing gradient strength at 298 K.
Figure 2. Dependence of T1 of the CH-protons of the tartaric acid building
blocks on the position in dendron 20.

3904
B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
Table 1. Diffusion coefficients and hydrodynamic radii RH of dendron 20 in
different solvents determined by 1H-PGSE NMR measurements
size on the solvent is evident. Whereas in the protic solvent
CD3OD an average diameter of 3 nm was determined, the
aprotic polar solvent CD3CN causes a more compressed size
of 2.6 nm. In DMSO the average diameter is 3 nm.
Solvent
D (m2/s)
RH (nm)
d (nm)
CD3OD
DMSO-d6
CD3CN
2.60£10210
7.30£10211
4.87£10210
1.54
1.55
1.29
3.08
3.10
2.58
Based on the results of the NMR experiments we conclude,
that depending on the solvent, different conformations
evolve in the third generation dendrons, as demonstrated
with the example of 20. We assume that in CD3OD it adopts
an (open) structure which allows free interaction of the
solvent molecules with the interior functionalities. In
CD3CN a more compact structure is developed leading to
a reduced size and to restricted segmental mobilities.19
where g is the gyromagnetic ratio, d is the duration of the
gradient pulse, D is the delay between the gradient pulses, D
is the diffusion coefficient, g is the gradient strength and 2N
denotes the period of the gradient pulse. The self diffusion
coefficients were now determined from the slope of ln (I/Io)
versus g 2.
2.2.4. Optical rotation measurements. The chiroptical
properties of all dendrons have been investigated in order to
determine the significance of the chiral repeating units on
the structure of the whole dendron. The optical activity of
the chiral dendrons have been normalized to the number of
chiral repeating units and compared to the optical activity
of first generation dendrons 7 and 8, respectively. Devia-
tions from the estimated values indicate the establishment of
preferred chiral conformations of the dendrons.8 Specific
([a]D) and molar rotations ([f]D) of the dendrons 7, 8, 13–
15 and 19–21 were recorded in CH3OH (Table 2) and in
CH3CN (Table 3). In an initial comparison of the molar
rotation per chiral subunit as a function of generation we
observed for the dendrons 13–21 a decrease with increasing
dendron generation (Fig. 4). The [f]D/n-values (n number
of chiral repeating units) for second generation dendrons 13
and 14 are 35% (CH3OH) smaller than that for first shell
Figure 3 shows a 2D NMR spectrum of 20 in DMSO-d6. The
decay of the signal intensity is displayed in relation of
chemical shift to gradient strength. However, the behaviour
of 20 in CD3OD compared to 20 in CD3CN is quite
different. The decay is considerably slower, which is based
on a smaller diffusion coefficient and therefore on a larger
molecular size. The Stokes–Einstein equation was used to
determine the hydrodynamic radii RH from the obtained
diffusion coefficients:
kBT
RH ¼
ð2Þ
6phD
where kB is the Boltzmann constant, T is the absolute
temperature and h is the viscosity of the solvent. The results
are combined in Table 1. The dependence of the dendron
Table 2. Chiroptical data for dendrons 7–23 in MeOH
a
b
Compound
Observed [a]D
Observed [f]D
Concentrationc
Estimated [f]Dd/deviatione (%)
8
261
250
244
þ61
þ54
þ61
þ6
2394
2760
21431
þ925
þ1785
þ395
þ50
0.202
0.184
0.204
0.202
0.218
0.210
0.123
0.122
–
2738 (3)
14
20
15
21
7
21426 (,1)
þ840 (9)
þ1631 (9)
–
–
–
22
23
26
249
a
Specific rotation (1021 deg cm2 g21).
Molar rotation (10 deg cm2 mol21).
Concentration (g 100 ml21).
Molar rotation (10 deg cm2 mol21).
In brackets.
b
c
d
e
Table 3. Chiroptical data for dendrons 7–23 in CH3CN
a
b
Compound
Observed [a]D
Observed [f]D
Concentrationc
Estimated [f]Dd/deviatione (%)
8
240
225
221
þ42
þ39
þ40
þ6
2262
2389
2715
þ655
þ1273
þ261
þ53
0.215
0.212
0.130
0.194
0.188
0.218
0.102
0.104
–
2471 (17)
14
20
15
21
7
2889 (20)
þ575 (14)
þ1096 (16)
–
–
–
22
23
26
254
a
Specific rotation (1021 deg cm2 g21).
Molar rotation (10 deg cm2 mol21).
Concentration (g 100 ml21).
Molar rotation (10 deg cm2 mol21).
In brackets.
b
c
d
e

B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
3905
model compound is needed. Based on 7, 8, 22 and 23 as
model units the agreement between the estimated and
observed [f]D-values of the homologue dendrons 13, 14, 19
and 20 is now in the range of 3% in MeOH (Table 2).
Dendrons 15 and 21 consisting of a mixture of natural and
unnatural tartaric acid building blocks deviate by ,9%.
This close match between the estimated and the observed
values leads to the conclusion that no additional chiral
folding of the entire dendrons 13, 14, 19 and 20 in CH3OH is
involved. Therefore the changes observed with increasing
dendron generation can be interpreted to be based solely on
constitutional changes in the dendron structure and are not
caused by a conformational ordering.8a The reason of the
deviation of the diastereomeric dendrons 15 and 20 from the
estimated [f]D -values remains unclear. Interestingly, when
the optical activity is calculated from the corresponding
[f]D-values of the constituting units obtained in CH3CN the
values disagree significantly more, on average by 18% for
all dendrons (Table 3). In fact the disagreement in aprotic
CH3CN relative to a close fit in CH3OH might suggest that
intramolecular communication of the chiral subunits in
CH3CN (but not in CH3OH) results in a fragile stabilization
of chiral conformations.
Figure 4. Molar optical rotations [F] per tartaric acid building block (first
generation) for dendrons 8, 14, 15, 20 and 21 in CH3OH and CH3CN.
dendrons 7 and 8. For third generation dendrons 19 and 20
the [f]D/n-values (from first to third generation) deviate by
48% (CH3OH). In CH3CN the deviation is 51% (13, 14)
(from first to second generation) and 61% (19, 20) (from
first to third generation), respectively. For the mixed
dendrons 15 and 21 we found a positive overall [f]D/n,
resulting in a disagreement of 58% (15) (from first to second
generation) and of 34% (21) (from first to third generation)
in CH3OH. In CH3CN the deviation is 60% (15) (from first
to second generation) and 42% (21) (from first to third
generation). However, the question is whether 7 and 8 are
suitable model compounds to rule out constitutional effects
resulting from different positions of the chiral units within
the dendron. The importance of suitable model compounds
was emphasized by McGrath et al.8a,b Thus, we chose 22
and 23 as model compounds for the first and second layers.
The only difference compared to the dendrons 7 and 8 is the
peripheral benzyl ester moiety. The polarimetry data show,
that this deviation distal to the asymmetric C-atoms does
greatly effect the optical activity. The replacement of
the benzylesters by an amide bonded alkyl group results in
a change in sign of the [f]D-value.20 In CH3OH the
[f]D-value of natural tartaric acid (R,R) derivative 22 is
slightly negative (-49), while the [f]D-value of first
generation dendron 7 (R,R) is positive (þ395) (Table 2).
In CH3CN the same is true (7; [f]D¼þ261) and 22;
[f]D¼254). The subunits within the periphery of the
second and third generation dendrons 13–15 and 19 –21
have identical constitutions and resemble the first shell
dendrons 7 and 8, respectively. Therefore no appropriate
2.2.5. Circular dichroism measurements. To gain further
information about the chiroptical properties of the depsi-
peptide dendrons, circular dichroism (CD) spectra were
recorded in CH3OH (Fig. 5) and CH3CN (Fig. 6).21 As a
measure of chirality the electronic p–pp transition of the
benzene chromophores at 237 nm can be used. As
Figure 5. CD spectra of 7, 8, 13, 14, 19 and 20 in CH3OH. (Mol. Ellip. in
[10 deg cm2 mol21]).

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B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
effects at 247 nm and at 215 nm in CH3OH. In CH3CN a
significant change in the spectra occurs and the latter Cotton
effect disappears. It is interesting to note the evaluation of
the magnitudes of the Cotton effects in these solvents. In
CH3OH the Cotton effects of the dendrons 13–15 and
19–21 are nearly proportional to the number of chromo-
phores present and the molar extinction coefficents increase
linearly with the generation number. By changing to the
aprotic solvent CH3CN this linear relationship was lost.
Whereas second generation dendrons 13 and 14 are roughly
in line, the increase in absorption going to the third
generation dendrons 19 and 20 is significantly enlarged
(Fig. 6) and is not proportional to the number of
chromophores present anymore. Even more pronounced is
this behavior in the spectra of the diastereomers 15 and 21
(Fig. 7). In CH3CN the third generation dendron 21 exhibits
a smaller Cotton effect than second generation dendron 15.
Whereas the CD-spectra measured in CH3OH do not
provide any indication about the formation of a chiral
superstructures the use of CH3CN as solvent for CD-investi-
gations suggests the possibility of stabilization of chiral
secondary structures.
Figure 6. CD spectra of 7, 8, 13, 14, 19 and 20 in CH3CN. (Mol. Ellip. in
[10 deg cm2 mol21]).
These results are in agreement with the NMR measurements
and the polarimetric data described above. It might be
assumed that the conformation of the dendrons in solution is
very sensitive to the conditions used. However, based on
the present data it cannot be decided whether this would be
single stable conformers or an equilibrium between several
forms including achiral folding motifs which is probably the
more likely situation.
determined from UV-spectra of compounds 7, 8, 22 and 23
the molar absorptivity (1) is roughly proportional to the
number of benzene chromophores in all solvents. The
maximum in the absorption spectra at 237 nm coincides
with a maximum in the CD spectra. However, first
generation dendrons 7 and 8 exhibit intra-chromophoric
excitonic coupling at 237 nm. On the contrary, with
increasing generation number the dendrons cannot adopt
prevailing conformations suitable for exciton coupling.22 In
CH3OH the second and third generation dendrons 14 and 20
display a positive Cotton effect at 237 nm and a negative
Cotton effect at 215 nm. The enantiomeric compounds 13
and 19 behave vice versa. In CH3CN the spectra do not
change shape significantly and the Cotton effects do not
shift. For dendrons 15 and 21, which consist of natural and
unnatural tartaric acid building blocks, the situation is
slightly different (Fig. 7). Both display positive Cotton
2.3. Chirality transfer
The ability to transmit chiral information over compara-
tively large distances represents an important factor in
applications such as catalysis and molecular recognition,
which are envisaged for dendritic macromolecules.23
Therefore we were interested if the chiral information
embodied in our dendrons could be transferred to the focal
point. In an initial concept the focal amino-functionalities of
the dendrons were connected to 9-anthracene carboxylic
acid (Schemes 4 and 5). The synthesis was straightforward
and conditions normally used for peptide coupling were
applied.11 To test whether the chiral information was
transferred we recorded CD-spectra in CH3OH in the region
of the absorption of the anthracene chromophore. In fact a
new cotton effect appeared at the absorptionn of the
anthracene chromophore (254 nm) (Fig. 8). As a preliminary
result we can conclude, that the microenvironment around the
focal group is distinctively chiral. In a further examination we
will test if there is an amplification of chirality under modified
conditions (e.g. temperature and solvent).
3. Summary and conclusions
We have prepared a new series of chiral depsipeptide
dendrons consisting of natural and unnatural tartaric acid
building blocks as branching units and v-aminocapronic
acid as spacer. These monodisperse systems reaching
molecular weights up to 3284 amu were completely charac-
terized by FAB-MS, 1H/13C NMR- and UV/Vis-spectroscopy.
Figure 7. CD spectra of 15 and 21 in CH3OH and CH3CN. (Mol. Ellip. in
[10 deg cm2 mol21]).

B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
3907
Scheme 4. (a) DCC, HOBt, NEt3, CH2Cl2; (b) DCC, HOBt, NEt3, CH2Cl2.
Scheme 5. (a) DCC, HOBt, NEt3, CH2Cl2.

3908
B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
JEOL EX 400, and JEOL A 500. The chemical shifts are
given in ppm relative to SiMe4 or the solvent peak as
standard reference. The resonance multiplicity is indicated
as s (singlet), d (doublet), t (triplet), q (quartet) and m
(multiplet). Broad resonances are described as broad (b).
PGSE NMR experiments were carried out on a JEOL A 500
equipped with an actively shielded gradient probehead
(max. Gradient strength¼1.4 T/m). A BPP-LED pulse
sequence18b,c with a gradient pulse width d¼1 ms and a
delay between the gradient pulses D¼150 ms resp.
D¼75 ms was used. The gradient strength g was calibrated
using the diffusion coefficient of HDO in D2O.24 1H NMR
Relaxation times were recorded on a JEOL A 500 by the
standard inversion recovery method. Mass spectra were
measured with Micromas Zab Spec (FAB) on a Finnigan
MAT 900 with 3-Nitrobenzylicalkohol as the matrix. IR
spectra were recorded on Bruker FT-IR IFS 88. Circular
dichroism (CD) measurements were carried out using
optical grade solvents and quartz glass cuvettes with a
10 mm path length. Optical rotations were performed on a
Schmidt&Haensch Digitalpolarimeter Polatronic E polari-
meter. UV spectroscopy was performed using a UV-3102 by
Shimadzu. Materials and solvents were obtained from
commercial suppliers and were used without further
purification. Products were isolated by flash column
chromatography (FC) (silica gel 60, particle size 0.04–
0.063 nm, Merck).
Figure 8. CD spectra of 24–29 in CH3OH. (Mol. Ellip. in
[10 deg cm2 mol21]).
The 1H NMR spectra were recorded in various solvents
(DMSO-d6, CDCl3, CD3CN and CD3OD) and suggest, that
the conformation of the dendrons is to some extent determined
by the solvent. This is supported by 1H NMR relaxation and
1H-PGSE NMR measurements. 1H-PGSE NMR measure-
ments permit direct determination of molecular sizes in
solution and indicate significant differences in CD3CN and
CD3OD. T1-relaxation times point to different segmental
mobilities of the chiral units in different solvents. Analysis of
the chiroptical properties show that observed changes in
optical activity with increasing generation can be explained by
constitutional effects of the dendron structure in CH3OH but
not in CH3CN. The latter findings are in agreement with CD
measurements which revealed a linear increase of the Cotton
effects with increasing generation number for CH3OH but not
for CH3CN as solvent. In CH3CN the linear dependence of the
Cotton effects on the number of benzene chromophores
present was lost. Based on these results we conclude, that
conformer equilibria within dendrons are very sensitive to the
environmental conditions. The chiroptical data might then be
explained by a stabilization of a chiral secondary structure in
CH3CN. However, based on the present data it cannot be
decided whether this would be single stable conformers or an
equilibrium between several forms including achiral folding
motifs. In any case, further studies are necessary to rationalize
the observed phenomena. In preliminary experiments we
showed that chirality transfer to the focal group of the
dendrons occurs. In future studies we will investigate whether
the chirality is amplified by varying the conditions.
Furthermore we are going to systematically replace the
v-aminocapronic acid spacer by other amino acids and
peptides. The resulting depsipeptide dendrimers will be
interesting mimics for peptide microenvironments found in
nature.
4.1. General procedure I for the synthesis of R,R- and
S,S-dibenzyl 2,3-dihydroxysuccinate
Tartaric acid (1 mol) and p-toluenesulfonic acid (0.05 mol)
were dissolved in 200 ml benzene and freshly distilled
benzyl alcohol (2.1 mol) was added. The suspension was
heated to 1078C and the evolving water was collected in a
Dean Stark apparatus. After 24 h the mixture was allowed to
cool down and 150 ml diethylether were added. The
solution was washed three times with saturated aqueous
sodium chloride (3£200 ml) and saturated aqueous sodium
hydrogencarbonate (3£150 ml) and then dried over MgSO4
and concentrated in vacuo.
4.2. General procedure II for the ester formation
The carboxylic acid (0.3 mol) and 4-dimethylaminopyridine
(DMAP) (0.01 mol) and hydroxybenzotriazole (HOBt)
(0.3 mol) were added to a solution of the alcohol
(0.3 mol) in CH2Cl2 (150 ml). Dicyclohexyl carbodiimide
(DCC) (0.35 mol) was added all at once at room
temperature and after 20 min the first dicyclohexylurea
(DCU) was formed. The suspension was stirred overnight.
The precipitate of DCU was filtered and the solution washed
with 10% aqueous hydrochloric acid HCl (1£100 ml) and
with saturated aqueous sodium hydrogencarbonate
(NaHCO3) (3£150 ml) and concentrated in vacuo. The
residue was dissolved in a little CH2Cl2 and hexane was
added to precipitate a white solid. The product was filtered
off, washed with further hexane and dried in vacuo.
4.3. General procedure III for the amide formation11
4. Experimental
The diacid (2.5 mmol) was dissolved in CH2Cl2 (50 ml) and
then triethylamine (NEt3) (5 mmol), HOBt (5 mmol) and
1H and 13C NMR spectra were recorded on JEOL GX 400,

B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
3909
the amine (5 mmol) were added. After cooling the solution
to 08C DCC (5 mmol) was added and the mixture was
stirred for 24 h. The white precipitate of dicyclohexylurea
(DCU) was filtered, the CH2Cl2 layer was washed once with
10% HCl (80 ml) and three times with a saturated aqueous
solution of NaHCO3 (3£50 ml). After removal of the
solvent the crude product was purified by FC.
(330.3): calcd: C 65.45, H 5.49 found: C 65.31, H 5.30;
[a]2D0¼-16.2 (c¼1.204, CH2Cl2).
4.5.4. R,R-Dibenzyl 2-(benzoyloxy) 3-hydroxysuccinate
(5). Compound 5 was synthesized according to general
procedure II with R,R-dibenzyl 2,3-dihydroxysuccinate (3)
(99.3 g; 0.3 mol) and benzoic acid (36.7 g; 0.3 mol). Yield
1
49.76 g, 0.11 mol, 38%, white solid. H NMR (400 MHz,
3
3
4.4. General procedure IV for the removal of the Bn
ester
CDCl3): d 3.27 (d, J¼7.6 Hz, 1H, OH), 4.89 (dd, J¼
7.6 Hz, 3J¼2.4 Hz, 1H, pCH), 5.10 (d, 2J¼12 Hz, 2H,
2
3
CH2-Bn), 5.23 (d, J¼12 Hz, 2H, CH2-Bn), 5.67 (d, J¼
2.4 Hz, 1H, pCH), 7.10 (m, 3H, Bn-Ph), 7.18 (m, 2H,
Bn-Ph), 7.31 (m, 5H, Bn-Ph), 7.37 (m, 2H, Bz-Ph), 7.56 (m,
1H, Bz-Ph), 7.90 (m, 2H, Bz-Ph); 13C NMR (100.6 MHz,
CDCl3): d 67.6, 68.3 (CH2-Bn), 70.6, 70.7 (pCH), 128.1,
128.3, 128.4, 128.44, 128.5, 128.6, 128.9 (Ph), 133.5, 134.3,
134.9 (q-Ph), 165.0, 166.3, 170.7 (CvO); MS (FAB): m/z
(%): 435 (85) [MþH]þ, 307 (41), 182 (100); C25H22O7
(434.3): calcd: C 69.12, H 5.10 found: C 69.11, H 5.30;
[a]2D0¼þ37.1 (c¼1.1400, CH2Cl2).
The Bn ester was dissolved in CH3OH and 10 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 aluminium oxide and
CH3OH was evaporated. The product was dried in vacuo.
4.5. General procedure V for the removal of the tert-
butoxycarbonyl (BOC) protecting group11
The BOC-protected amine (5 mmol) was dissolved in
CH2Cl2 (10 ml) and 99% trifluroacetic acid (10 ml) was
added. After 45 min the reaction was complete and the
solvent was evaporated. The viscous oil was dried for a
further 24 h in vacuo.
4.5.5. S,S-Dibenzyl 2-(benzoyloxy) 3-hydroxysuccinate
(6). Compound 6 was synthesized according to general
procedure II with S,S-dibenzyl 2,3-dihydroxysuccinate (4)
(99.3 g; 0.3 mol) and benzoic acid (36.7 g; 0.3 mol). Yield
1
26.95 g, 0.062 mol, 31%, white solid. H NMR (400 MHz,
3
3
4.5.1. 6-[(tert-Butoxycarbonyl)amino]hexanoic acid.
6-[(tert-Butoxycarbonyl)amino]hexanoic acid was prepared
according to the literature procedure.11 1H NMR (400 MHz,
CDCl3): d 3.26 (d, J¼8 Hz, 1H, OH), 4.89 (dd, J¼8 Hz,
3J¼3 Hz, 1H, pCH), 5.11 (d, 2J¼12 Hz, 2H, CH2-Bn), 5.21
2
3
p
(d, J¼12 Hz, 2H, CH2-Bn), 5.67 (d, J¼3 Hz, 1H, CH),
7.10 (m, 3H, Bn), 7.19 (m, 2H, Bn), 7.32 (m, 5H, Bn), 7.37
(m, 2H, Bz), 7.56 (m, 1H, Bz), 7.90 (m, 2H, Bz); 13C NMR
(100.6 MHz, CDCl3): d 67.4, 68.2 (CH2-Bn), 70.6, 70.7
(pCH), 128.1, 128.2, 128.4, 128.45, 128.5, 128.7, 128.9
(Ph), 133.5, 134.3, 134.9 (q-Ph), 164.9, 166.3, 170.9
(CvO); MS (FAB): m/z (%): 435 (75) [MþH]þ, 307
(41), 182 (100); C25H22O7 (434.3): calcd: C 69.12, H 5.10
found: C 69.21, H 4.95; [a]2D0¼-37.4 (c¼1.302, CH2Cl2).
3
CDCl3): d 1.42 (m, 13H, BOC-CH3, CH2), 1.6 (quin., J¼
3
7.5 Hz, 2H, CH2), 2.31 (t, J¼7.2 Hz, CH2COO), 3.07 (br,
2H, CH2N), 4.56 (br, 1H, NH), 11.6 (br, 1H, COOH);
13C NMR (100.6 MHz, CDCl3): d 24.2, 26.1 (CH2), 28.4
(BOC-CH3), 29.4 (CH2), 33.9 (CH2COO), 40.3 (CH2),
41.4 (CH2N), 79.2 (BOC-C), 156.1 (BOC-CvO), 179.2
(COOH); MS (FAB): m/z (%): 463 (16) [2£M]þ, 232 (40)
[MþH]þ, 176 (100) [M2t-Butyl]þ; C11H21O4N (231.3):
calcd: C 57.13, H 9.15, N 6.02; found: C 57.11, H 9.40, N
6.13.
4.5.6. Compound 7, dendron first generation. Compound
7 was synthesized according to general procedure II with
6-[(tert-butoxycarbonyl)amino]hexanoic acid (13.96 g,
0.06 mol) and R,R-dibenzyl 2-(benzoyloxy) 3-hydroxy-
succinate (5) (26.21 g, 0.06 mol). The white precipitate
was filtered off and the organic phase was evaporated to
provide product.
4.5.2. R,R-Dibenzyl 2,3-dihydroxysuccinate (3). Com-
pound 3 was synthesized according to general procedure I
with R,R-tartaric acid (1) (150.09 g, 1 mol). Yield 303.8 g,
0.92 mol, 92%, white solid. 1H NMR (400 MHz, CDCl3): d
3
p
3.3 (br, 2H, OH), 4.60 (d, J¼3.6 Hz, 2H, CH), 5.22 (d,
2J¼12 Hz, 2H, CH2-Bn), 5.29 (d, 2J¼12 Hz, 2H, CH2-Bn),
7.36 (m, 10H, Ph); 13C NMR (100.6 MHz, CDCl3): d 68.0
(CH2-Bn), 72.1 (pCH), 128.3, 128.4, 128.7 (Ph), 134.7
(q-Ph), 171.3 (CvO); MS (FAB): m/z (%): 353 (9)
[MþNa]þ, 331 (24) [MþH]þ, 181 (100); C18H18O6 (330.3):
calcd: C 65.45, H 5.49 found: C 65.11, H 5.40; [a]2D0¼þ16.6
(c¼1.290, CH2Cl2).
1
Yield 29.5 g, 0.046 mol, 76%, viscous, colorless oil. H
NMR (400 MHz, CDCl3): d 1.40 (m, 15H, BOC-CH3, CH2),
2.14 (quin, J¼7.6 Hz, 1H, CHCOO), 2.27 (quin, J¼7.6 Hz,
1H, CHCOO), 3.05 (m, 2H, CH2N), 4.49 (br, 1H, NH),
2
2
5.03 (d, J¼12 Hz, 1H, CH2-Bn), 5.10 (d, J¼12 Hz, 1H,
2
2
CH2-Bn), 5.15 (d, J¼12 Hz, 1H, CH2-Bn), 5.20 (d, J¼
12 Hz, 1H, CH2-Bn), 5.80 (d, 3J¼2.8 Hz, 1H, pCH), 5.91 (d,
p
4.5.3. S,S-Dibenzyl 2,3-dihydroxysuccinate (4). Com-
pound 4 was synthesized according to general procedure I
with S,S-tartaric acid (2) (50 g, 0.33 mol). Yield 99.2 g,
3J¼2.8 Hz, 1H, CH), 7.09 (m, 3H, Bn), 7.10 (m, 2H, Bn),
7.29 (m, 5H, Bn), 7.37 (m, 2H, Bz), 7.54 (m, 1H, Bz), 7.92
(m, 2H, Bz); 13C NMR (100.6 MHz, CDCl3): d 24.2, 26.0
(CH2), 28.4 (BOC-CH3), 29.6 (CH2), 29.6 (CH2COO),
40.3 (CH2N), 67.7, 67.8 (CH2-Bn), 70.7, 71.2 (pCH), 79.0
(q-BOC), 128.3, 128.4, 128.5, 128.5, 128.6, 130.1 (Ph),
133.6, 134.5, 134.8 (q-Ph), 155.9 (BOC-CvO), 165.0,
165.6, 165.7, 172.1 (CvO); MS (FAB): m/z (%): 648 (12)
[MþH]þ, 592 (11) [M2t-Butyl]þ, 548 (100) [M-BOC]þ;
C36H41O10N (647.4): calcd: C 66.80, H 6.38, N 2.16; found:
1
0.3 mol, 91%, white solid. H NMR (400 MHz, CDCl3): d
3
3
p
3.25 (d, J¼7 Hz, 2H, OH), 4.60 (d, J¼7 Hz, 2H, CH),
2
2
5.22 (d, J¼12 Hz, 2H, CH2-Bn), 5.29 (d, J¼12 Hz, 2H,
CH2-Bn), 7.35 (m, 10H, Ph); 13C NMR (100.6 MHz,
CDCl3): d 68.0 (CH2-Bn), 72.1 (pCH), 128.3, 128.4, 128.6
(Ph), 134.7 (q-Ph), 171.3 (CvO); MS (FAB): m/z (%): 353
(15) [MþNa]þ, 331 (5) [MþH]þ, 181 (100); C18H18O6

3910
B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
C 67.11, H 6.40, N 2.23; UV/Vis (CH3CN) lmax (1) (nm):
274, 268, 263, 231 (12800); UV/Vis (CH3OH) lmax (1)
(nm): 274, 268, 263, 231 (12700); [a]2D0¼þ34.4 (c¼1.202,
CH2Cl2).
2H, CH2N), 5.04 (d, 2J¼12 Hz, 1H, Bn), 5.09 (d, 2J¼12 Hz,
2
1H, CH2-Bn), 5.13 (d, J¼12 Hz, 1H, CH2-Bn), 5.25 (d,
2J¼12 Hz, 1H, CH2-Bn), 5.81 (d, 3J¼3 Hz, 1H, pCH), 5.92
(d, 3J¼3 Hz, 1H, pCH), 7.09 (m, 5H, Bn), 7.29 (m, 5H, Bn),
7.39 (m, 2H, Bz), 7.57 (m, 1H, Bz), 7.90 (m, 2H, Bz), 10.1
(br, 2H, NH2); 13C NMR (100.6 MHz, CDCl3): d 23.4,
25.1, 26.7 (CH2), 32.8 (CH2COO), 39.9 (CH2N), 67.8, 68.1
(CH2-Bn), 70.8, 71.1 (pCH), 115.0 (q, 1J(C,F)¼284 Hz,
TFA), 128.2, 128.3, 128.4, 128.5, 128.6, 128.7, 129.9 (Ph),
4.5.7. Compound 8, dendron first generation. Compound
8 was synthesized according to general procedure II with
6-[(tert-butoxycarbonyl)amino]hexanoic acid (13.96 g,
0.06 mol) and S,S-dibenzyl 2-(benzoyloxy) 3-hydroxy-
succinate (6) (26.21 g, 0.06 mol). The white precipitate
was filtered off and the organic phase was evaporated to
provide product.
2
133.8, 134.3, 134.7 (q-Ph), 163 (q, J(C,F)¼44 Hz, TFA),
165.0, 165.7, 165.8, 172.1 (CvO); MS (FAB): m/z (%): 548
(100) [M]þ, 458 (5) [M2Bn]þ, 431 (23).
1
Yield 29.2 g, 0.045 mol, 75%, viscous, colorless oil. H
4.5.10. Compound 11, dendron first generation (COOH).
Compound 11 was synthesized according to general
procedure IV with compound 7 (2.97 g; 4.59 mmol) and
10% Pd/C (122 mg) in CH3OH (250 ml). Yield 2.13 g,
4.54 mmol, 99%, white solid. 1H NMR (400 MHz, CDCl3):
d 1.41 (br, 13H, CH2, BOC-CH3), 1.62 (br, 2H, CH2), 2.35
(m, 1H, CHCOO), 2.40 (br, 1H, CHCOO), 2.97 (br, 1H,
CH2N), 3.12 (br, 1H, CH2N), 5.86 (br, 2H, pCH), 6.23
(b, 1H, NH), 7.38 (m, 2H, Bz), 7.52 (m, 1H, q-Bz), 8.01 (m,
2H, Bz), 9.5 (br, 2H, COOH); 13C NMR (100.6 MHz,
DMSO): d 24.4, 25.8 (CH2), 28.6 (BOC-CH3), 29.4
(CH2COO), 33.5 (CH2NH), 71.1, 71.7 (pCH), 78.0
(q-BOC), 128.7, 129.4, 129.7 (Ph), 134.5 (q-Ph), 156.1
(BOC-CvO), 165.1, 167.6, 167.8, 172.5 (CvO); MS
(FAB): m/z (%): 600 (9) [MþCs]þ, 506 (30) [MþK]þ,
490 (89) [MþNa]þ, 468 (48) [MþH]þ, 412 (100) [M2
t-Butyl]þ; C22H29O10N (467.4): calcd: C 56.53, H 6.25, N
2.99; found: C 57.03, H 6.56, N 2.36.
NMR (400 MHz, CDCl3): d 1.41 (m, 15H, BOC-CH3, CH2),
2.20 (quin, J¼7.6 Hz, 1H, CHCOO), 2.27 (quin, J¼7.6 Hz,
1H, CHCOO), 3.06 (m, 2H, CH2N), 4.49 (br, 1H, NH), 5.03
(d, 2J¼12 Hz, 1H, CH2-Bn), 5.11 (d, 2J¼12 Hz, 1H,
2
2
CH2-Bn), 5.15 (d, J¼12 Hz, 1H, CH2-Bn), 5.21 (d, J¼
12 Hz, 1H, CH2-Bn), 5.80 (d, 3J¼2.8 Hz, 1H, pCH), 5.89 (d,
3J¼2.8 Hz, 1H, CH), 7.09 (m, 3H, Bn), 7.15 (m, 2H, Bn),
p
7.26 (m, 5H, Bn, 7.39 (m, 2H, Bz), 7.54 (m, 1H, Bz), 7.93
(m, 2H, Bz); 13C NMR (100.6 MHz, CDCl3): d 24.5, 25.9
(CH2), 28.2 (BOC-CH3), 29.6 (CH2), 29.6 (CH2COO), 40.1
(CH2N), 67.8, 67.9 (CH2-Bn), 70.7, 71.2 (pCH), 79.4
(q-BOC), 128.3, 128.4, 128.5, 128.5, 128.6, 130.3 (Ph),
133.7, 134.5, 134.8 (q-Ph), 155.6 (BOC-CvO), 164.8,
165.6, 165.7, 172.1 (CvO); MS (FAB): m/z (%): 648 (15)
[MþH]þ, 592 (10) [M2t-Butyl]þ, 548 (100) [M2BOC]þ;
C36H41O10N (647.4): calcd: C 66.80, H 6.38, N 2.16; found:
C 66.53, H 6.56, N 2.26; UV/Vis (CH3CN) lmax (1) (nm):
274, 268, 263, 231 (12800); UV/Vis (CH3OH) lmax (1)
(nm): 274, 268, 263, 231 (12700); [a]2D0¼-35.5 (c¼1.312,
CH2Cl2).
4.5.11. Compound 12, dendron first generation (COOH).
Compound 12 was synthesized according to general
procedure IV with compound 8 (3.86 g; 5.97 mmol) and
10% Pd/C (200 mg) in CH3OH (300 ml). Yield 2.59 g,
5.55 mmol, 93%, white solid. 1H NMR (400 MHz, CDCl3):
d 1.40 (br, 13H, CH2, BOC-CH3), 1.67 (br, 2H, CH2), 2.27
(m, 1H, CHCOO), 2.43 (br, 1H, CHCOO), 2.97 (br, 1H,
4.5.8. Compound 9, dendron first generation (NH2).
Compound 9 was synthesized according to general
procedure V with compound 7 (1.7 g; 2.62 mmol). Yield
1
1.72 g, 2.598 mmol, 99%, colorless, viscous oil. H NMR
p
(400 MHz, CDCl3): d 1.28 (m, 2H, CH2), 1.51 (m, 2H,
CH2), 1.60 (m, 2H, CH2), 2.15 (quin, J¼7.8 Hz, 1H,
CHCOO), 2.28 (quin, J¼7.8 Hz, 1H, CHCOO), 2.93 (br,
2H, CH2N), 5.04 (d, 2J¼12.4 Hz, 1H, CH2-Bn), 5.080
CH2N), 3.19 (br, 1H, CH2N), 5.79 (br, 2H, CH), 6.22 (br,
1H, NH), 7.38 (m, 2H, Bz), 7.53 (m, 1H, q-Bz), 8.07 (m, 2H,
Bz), 9.51 (br, 2H, COOH); 13C NMR (100.6 MHz, DMSO):
d 24.5, 25.8 (CH2), 28.3 (BOC-CH3), 29.6 (CH2COO), 33.8
(CH2NH), 70.7, 71.3 (pCH), 80.8 (q-BOC), 128.4, 128.7,
130.1 (Ph), 133.5 (q-Ph), 157.1 (BOC-CvO), 165.2, 167.6,
167.8, 172.3 (CvO); MS (FAB): m/z (%): 506 (42)
[MþK]þ, 490 (37) [MþNa]þ, 468 (38) [MþH]þ, 412
(50) [M2t-Butyl]þ, 368 (100) [M2BOC]þ; C22H29O10N
(467.4): calcd: C 56.53, H 6.25, N 2.99; found: C 57.12, H
6.47, N 2.56.
2
2
(d, J¼12.4 Hz, 1H, CH2-Bn), 5.12 (d, J¼12.4 Hz, 1H,
2
3
CH2-Bn), 5.29 (d, J¼12.4 Hz, 1H, CH2-Bn), 5.80 (d, J¼
p
3
p
2.8 Hz, 1H, CH), 5.91 (d, J¼2.8 Hz, 1H, CH), 7.09 (m,
4H, Ph), 7.21 (m, 4H, Ph), 7.49 (m, 5H, Ph), 7.89 (m, 2H,
Ph), 8.21 (br, 2H, NH2); 13C NMR (100.6 MHz, CDCl3): d
23.4, 25.1, 26.7 (CH2), 32.8 (CH2COO), 39.9 (CH2N), 67.8,
68.1 (CH2-Bn), 70.8, 71.1 (pCH), 115.0 (q, 1J(C,F)¼
284 Hz, TFA), 128.2, 128.3, 128.4, 128.5, 128.6, 128.7,
2
129.9 (Ph), 133.8, 134.3, 134.7 (q-Ph), 163 (q, J(C,F)¼
4.5.12. Compound 13, dendron second generation.
Compound 13 was synthesized according to general
procedure III with compound 12 (1.03 g; 2.2 mmol) and
compound 9 (TFA-adduct) (2.81 g; 4.4 mmol). The crude
product was purified by column chromatography (silica,
EtOAc/hexane, 1:1; Rf¼0.26).
44 Hz, TFA), 165.0, 165.7, 165.8, 172.1 (CvO); MS
(FAB): m/z (%): 1095 (4) [2pMþ], 548 (100) [MþH]þ, 458
(5) [M2Bn]þ, 431 (23).
4.5.9. Compound 10, dendron first generation (NH2).
Compound 10 was synthesized according to general
procedure V with compound 8 (4.6 g; 7.1 mmol). Yield
4.65 g, 7.0 mmol, 99%, colorless, viscous oil. 1H NMR
(400 MHz, CDCl3): d 1.33 (m, 2H, CH2), 1.54 (m, 2H,
CH2), 1.61 (m, 2H, CH2), 2.17 (quin, J¼7.8 Hz, 1H,
CHCOO), 2.28 (quin, J¼7.8 Hz, 1H, CHCOO), 2.97 (m,
Yield 800 mg, 0.52 mmol, 24%, white solid. 1H NMR
(500 MHz, CDCl3): d 1.39 (m, 27H, CH2, BOC-CH3), 2.16
(m, 4H, CH2COO), 2.38 (m, 2H, CH2COO), 3.03 (m, 2H,
CH2N), 3.21 (m, 4H, CH2N), 4.64 (br, 1H, NH), 5.03 (d,
2
2J¼6 Hz, 1H, CH2-Bn), 5.05 (d, J¼6 Hz, 1H, CH2-Bn),

B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
3911
5.09 (d, 2J¼6 Hz, 1H, CH2-Bn), 5.11 (d, 2J¼6 Hz, 1H,
product was purified by column chromatography (silica,
EtAc/hexane, 1:1; Rf¼0.15).
2
2
CH2-Bn), 5.17 (d, J¼6 Hz, 1H, CH2-Bn), 5.19 (d, J¼
2
6 Hz, 1H, CH2-Bn), 5.22 (d, J¼6 Hz, 1H, CH2-Bn), 5.25
2
3
p
(d, J¼6 Hz, 1H, CH2-Bn), 5.75 (d, J¼3 Hz, 1H, CH),
Yield 1.03 g, 0.675 mmol, 45%, white solid. 1H NMR
(400 MHz, CDCl3): d 1.39 (m, 27H, CH2, BOC-CH3), 2.17
(m, 4H, CH2COO), 2.37 (m, 2H, CH2COO), 3.03 (m, 2H,
CH2N), 3.20 (m, 4H, CH2N), 4.62 (br, 1H, NH), 5.02 (d,
3
p
3
p
5.77 (d, J¼3 Hz, 1H, CH), 5.80 (d, J¼3 Hz, 1H, CH),
3
p
3
p
5.82 (d, J¼3 Hz, 1H, CH), 5.89 (d, J¼3 Hz, 1H, CH),
5.91 (d, 3J¼3 Hz, 1H, pCH), 6.25 (br, 2H, NH), 7.09 (m, 6H,
Bn), 7.15 (m, 4H, Bn), 7.28 (m, 10H, Bn), 7.40 (m, 6H, Bz),
7.55 (m, 3H, q-Bz), 7.91 (m, 4H, Bz), 8.01 (m, 2H, Bz); 13C
NMR (125.6 MHz, CDCl3): d 23.9, 24.0, 24.3, 25.8, 25.9,
26.0 (CH2), 28.4 (BOC-CH3), 28.8, 28.9, 29.5 (CH2), 33.0,
33.1, 33.7 (CH2COO), 39.2, 39.3, 40.2 (CH2N), 67.7, 67.8,
67.9 (CH2-Bn), 70.7, 71.2, 71.25, 72.2, 72.7 (pCH), 79.0
(q-BOC), 128.3, 128.5, 128.6, 128.7, 129.9, 130.0, 133.6,
133.9, 134.5, 134.8 (Ph), 155.9 (BOC-CvO), 163.6, 164.9,
165.5, 165.6, 165.7, 166.0, 166.1, 171.8, 172.0 (CvO); MS
(FAB): m/z (%): 1526 (2) [MþH]þ, 1426 (79) [M2BOC]þ,
1336 (9) [M2BOC-Bn]þ, 548 (39); C84H91O24N3 (1526.6):
calcd: C 66.09, H 6.00, N 2.75; found: C 65.56, H 6.16, N
2.83; UV/Vis (CH3CN) lmax (1) (nm): 274, 269, 231
(37625); UV/Vis (CH3OH) lmax (1) (nm): 274, 268, 263,
231 (39700); [a]D20¼þ22.3 (c¼1.100, CH2Cl2).
2
2J¼9 Hz, 1H, CH2-Bn), 5.05 (d, J¼9 Hz, 1H, CH2-Bn),
5.09 (d, 2J¼6 Hz, 1H, CH2-Bn), 5.12 (d, 2J¼6 Hz, 1H,
2
2
CH2-Bn), 5.16 (d, J¼8 Hz, 1H, CH2-Bn), 5.19 (d, J¼
8 Hz, 1H, CH2-Bn), 5.22 (d, 2J¼10 Hz, 1H, CH2-Bn), 5.25
2
3
p
(d, J¼10 Hz, 1H, CH2-Bn), 5.72 (d, J¼3 Hz, 1H, CH),
3
p
3
p
5.77 (d, J¼3 Hz, 1H, CH), 5.80 (d, J¼5 Hz, 1H, -CH),
3
p
3
p
5.82 (d, J¼5 Hz, 1H, CH), 5.89 (d, J¼3 Hz, 1H, CH),
5.91 (d, 3J¼3 Hz, 1H, pCH), 6.24 (br, 2H, NH), 7.10 (m, 6H,
Bn), 7.15 (m, 4H, Bn), 7.28 (m, 10H, Bn), 7.38 (m, 6H, Bz),
7.55 (m, 3H, q-Bz), 7.91 (m, 4H, Bz), 8.01 (m, 2H, Bz); 13C
NMR (100.6 MHz, CDCl3): d 24.0, 24.1, 24.3, 24.9, 25.6,
25.9 (CH2), 28.4 (BOC-CH3), 28.9, 29.0, 29.6 (CH2), 33.1,
33.2, 33.7 (CH2COO), 39.3, 39.31, 40.2 (CH2N), 49.1, 67.7,
67.8 (CH2-Bn), 70.7, 71.2, 72.3, 72.7 (pCH), 78.9 (q-BOC),
128.3, 128.4, 128.5, 128.6, 128.7, 129.9, 130.0, 133.6,
133.9, 134.5, 134.8 (Ph), 155.9 (BOC-CvO), 165.0, 165.6,
165.7, 166.0, 166.1, 171.8, 172.0 (CvO); MS (FAB): m/z
(%): 1527 (2) [MþH]þ, 1427 (100) [M2BOC]þ, 1336 (9)
[M2BOC-Bn]þ, 548 (9); C84H91O24N3 (1526.6): calcd: C
66.09, H 6.00, N 2.75; found: C 65.86, H 6.13, N 2.86;
UV/Vis (CH3CN) lmax (1) (nm): 274, 268, 263, 231
(37600); UV/Vis (CH3OH) lmax (1) (nm): 274, 268, 263,
231 (39100); [a]D20¼þ35.6 (c¼0.926, CH2Cl2).
4.5.13. Compound 14, dendron second generation.
Compound 14 was synthesized according to general
procedure III with compound 12 (1.64 g; 3.5 mmol) and
compound 10 (TFA-adduct) (2.81 g; 4.4 mmol). The crude
product was purified by column chromatography (silica,
EtOAc/hexane, 1:1; Rf¼0.26).
Yield 1.2 g, 0.78 mmol, 23%, white solid. 1H NMR
(400 MHz, CDCl3): d 1.40 (m, 27H, CH2, BOC-CH3),
2.15 (m, 4H, CH2COO), 2.35 (m, 2H, CH2COO), 3.03 (m,
2H, CH2N), 3.21 (m, 4H, CH2N), 4.62 (br, 1H, NH), 5.03 (d,
4.5.15. Compound 16, dendron second generation (NH2).
Compound 16 was synthesized according to general
procedure V with compound 13 (700 mg; 4.6 mmol) and
99% trifluoroacetic acid (8 ml) in CH2Cl2 (8 ml).
2
2J¼6 Hz, 1H, CH2-Bn), 5.06 (d, J¼6 Hz, 1 H, CH2-Bn),
5.09 (d, 2J¼6 Hz, 1H, CH2-Bn), 5.12 (d, 2J¼6 Hz, 1H,
2
2
CH2-Bn), 5.16 (d, J¼6 Hz, 1H, CH2-Bn), 5.19 (d, J¼
Yield 710 mg, 4.58 mmol, 99%, viscous oil. 1H NMR
(500 MHz, CDCl3): d 1.41 (m, 18H, CH2), 2.07 (m, 4H,
CH2COO), 2.25 (m, 2H, CH2COO), 2.97 (br, 2H, CH2N),
3.19 (m, 4H, CH2N), 5.01 (d, 2J¼6 Hz, 1H, CH2-Bn), 5.04
(d, 2J¼6 Hz, 1H, CH2-Bn), 5.09 (d, 2J¼6 Hz, 1H, CH2-Bn),
2
4 Hz, 1H, CH2-Bn), 5.21 (d, J¼6 Hz, 1H, CH2-Bn), 5.25
2
3
p
(d, J¼4 Hz, 1H, CH2-Bn), 5.72 (d, J¼3 Hz, 1H, CH),
3
p
3
p
5.77 (d, J¼3 Hz, 1H, CH), 5.80 (d, J¼3 Hz, 1H, CH),
3
p
3
p
5.82 (d, J¼3 Hz, 1H, CH), 5.89 (d, J¼3 Hz, 1H, CH),
5.91 (d, 3J¼3 Hz, 1H, pCH), 6.24 (br, 2H, NH), 7.09 (m, 6H,
Bn), 7.15 (m, 4H, Bn), 7.28 (m, 10H, Bn), 7.42 (m, 6H, Bz),
7.56 (m, 3H, q-Bz), 7.91 (m, 4H, Bz), 8.02 (m, 2H, Bz); 13C
NMR (100.6 MHz, CDCl3): d 23.9, 24.0, 24.3, 25.8, 25.9,
26.0 (CH2), 28.4 (BOC-CH3), 28.8, 28.9, 29.5 (CH2), 33.1,
33.2, 33.7 (CH2COO), 39.2, 39.3, 40.1 (CH2N), 67.7, 67.8,
67.9 (CH2-Bn), 70.7, 71.2, 71.3, 72.2, 72.7 (pCH), 78.9
(q-BOC), 128.3, 128.43, 128.47, 128.5, 128.6, 129.9, 130.0,
133.6, 133.4, 134.5, 134.8 (Ph), 155.9 (BOC-CvO), 164.9,
165.5, 165.6, 165.7, 166.0, 166.1, 171.8, 172.0 (CvO);
MS (FAB): m/z (%): 1526 (5) [MþH]þ, 1426 (100)
[M2BOC]þ, 1336 (11) [M2BOC-Bn]þ; C84H91O24N3
(1526.6): calcd: C 66.09, H 6.00, N 2.75; found: C
64.96, H 6.13, N 2.76; UV/Vis (CH3CN) lmax (1) (nm):
274, 268, 263, 231 (37600); UV/Vis (CH3OH) lmax (1)
(nm): 274, 268, 263, 231 (39000); [a]2D0¼-21.1 (1.092,
CH2Cl2).
2
2
5.12 (d, J¼6 Hz, 1H, CH2-Bn), 5.17 (d, J¼12 Hz, 1H,
2
CH2-Bn), 5.21 (d, J¼12 Hz, 1H, CH2-Bn), 5.72 (m, 2H,
pCH), 5.80 (m, 2H, pCH), 5.91 (m, 2H, pCH), 7.2 (m, 26H,
Ph), 7.91 (m, 9H, Ph); 13C NMR (125.6 MHz, CDCl3): d
23.4, 23.7, 23.8, 23.9, 24.5, 25.4, 25.7, 28.3, 28.5 (CH2),
32.5, 33.0, 33.1 (CH2COO), 39.6, 39.7, 40.0 (CH2N), 67.8,
67.9 (CH2-Bn), 70.8, 71.2, 72.3, (pCH), 115.0 (q, 1J(C,F)¼
284 Hz, TFA), 127.8, 128.2, 128.4, 128.5, 128.51, 128.6,
128.8, 129.8, 129.9, 133.7, 134.4, 134.7 (Ph), 163 (q,
2J(C,F)¼44 Hz, TFA), 160.2, 164.9, 165.0, 165.7, 167.4,
167.5, 171.8, 172.2, 172.3 (CvO); MS (FAB): m/z (%):
1427 (100) [MþH]þ, 1337 (8) [M2Bn]þ, 912 (30).
4.5.16. Compound 19, dendron third generation. Com-
pound 19 was synthesized according to general procedure
III with compound 16 (TFA adduct) (570 mg; 0.4 mmol)
and with compound 11 (94 mg; 0.2 mmol). The crude
product was purified by column chromatography (silica,
CH2Cl2/MeOH, 25:1; Rf¼0.15).
4.5.14. Compound 15, dendron second generation.
Compound 15 was synthesized according to general
procedure III with compound 12 (0.7 g; 1.5 mmol) and
compound 11 (TFA-adduct) (1.64 g; 3.0 mmol). The crude
Yield 230 mg, 0.07 mmol, 18%, white solid. 1H NMR
(400 MHz, CDCl3): d 1.39 (m, 47H, CH2, BOC-CH3), 1.66

3912
B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
(s, 4H), 2.20 (m, 14H, CH2COO), 3.16 (m, 14H, CH2N),
4.77 (br, 1H, NHBOC), 5.15 (m, 16H, CH2-Bn), 5.85 (m,
14H, pCH), 6.50 (br, 4H, NH), 6.61 (br, 2H, NH), 7.07 (m,
12H, Ph), 7.14 (m, 8H, q-Bn), 7.27 (m, 20H, Bn), 7.37 (m,
14H, Bz), 7.53 (m, 7H, q-Bz), 7.90 (m, 8H, Bz), 8.00 (m,
6H, Bz); 13C NMR (100.6 MHz, CDCl3): d 24.0, 24.3, 24.9,
25.6, 25.9 (CH2), 28.4 (BOC-CH3), 28.8, 28.9, 29.5 (CH2),
33.1, 33.2, 33.6, 33.7, 33.9 (CH2COO), 39.0, 39.3, 40.2
(CH2N), 67.7, 67.8 (CH2-Bn), 70.7, 71.1, 71.2, 72.4, 72.8,
72.9 (pCH), 78.9 (q-BOC), 128.3, 128.4, 128.5, 128.6,
128.7, 129.9, 130.0, 133.7, 133.9, 134.5, 134.7 (Ph), 156.6
(BOC-CvO), 165.0, 165.5, 165.7, 166.1, 171.9, 172.1
(CvO); MS (FAB): m/z (%): 3183 (49) [M2BOC]þ, 1832
(88), 1427 (100); C180H191O52N7 (3284.3): calcd: C 65.81,
H 5.87, N 2.99; found: C 65.04, H 6.12, N 3.38; UV/Vis
(CH3CN) lmax (1) (nm): 274, 268, 231 (83250); UV/Vis
(CH3OH) lmax (1) (nm): 268, 231 (81600); [a]2D0¼þ12.7
(c¼1.060, CH2Cl2).
20H, Bn), 7.37 (m, 14H, Bz), 7.53 (m, 7H, q-Bz), 7.90 (m,
8H, Bz), 8.01 (m, 6H, Bz); 13C NMR (100.6 MHz, CDCl3):
d 24.0, 24.3, 24.9, 25.6, 25.8, 25.9 (CH2), 28.3 (BOC-CH3),
28.6, 28.7, 28.8, 29.1, 29.5 (CH2), 33.1, 33.7, 33.9
(CH2COO), 38.9, 39.0, 39.2, 39.3 (CH2N), 67.7, 67.8
(CH2-Bn), 70.7, 71.1, 71.2, 72.3, 72.8, 73.1 (pCH), 128.3,
128.4, 128.5, 128.6, 130.0, 128.6, 133.6, 133.8, 133.9,
134.4, 134.7 (Ph), 156.7 (BOC-CvO), 164.9, 165.5, 165.7,
166.1, 166.2, 168.5, 171.9, 172.0 (CvO); MS (FAB): m/z
(%): 3283 (1) [M]þ, 3183 (65) [M2BOC]þ, 3093 (3)
[M2BOC-Bn]þ, 1313 (62), 548 (100); C180H191O52N7
(3284.3): calcd: C 65.81, H 5.87, N 2.99; found: C 65.26, H
5.88, N 2.87; UV/Vis (CH3CN) lmax (1) (nm): 274, 268, 231
(83200); UV/Vis (CH3OH) lmax (1) (nm): 268, 231
(81600); [a]2D0¼þ30.9 (c¼0.500, CH2Cl2).
4.5.19. Compound 22, model compound. Compound 22
was synthesized according to general procedure III with
compound 11 (185 mg; 0.39 mmol) and benzyl 6-amino-
hexanoate11 (311 mg; 0.8 mmol). The crude product was
purified by column chromatography (silica, CH2Cl2/MeOH,
20:1; Rf¼0.36).
Yield 157 mg, 0.18 mmol, 45%, white solid. 1H NMR
(400 MHz, CDCl3): d 1.40 (m, 27H, BOC-CH3, CH2), 2.30
(m, 6H, CHCOO), 3.15 (m, 6H, CH2N), 4.61 (br, 1H, NH),
4.5.17. Compound 20, dendron third generation. Com-
pound 20 was synthesized according to general procedure
III with compound 17 (TFA adduct) (820 mg; 0.5 mmol)
and with compound 12 (117 mg; 0.2 mmol). The crude
product was purified by column chromatography (silica,
CH2Cl2/MeOH, 25:1; Rf¼0.15).
Yield 264 mg, 0.07 mmol, 17%, white solid. 1H NMR
(400 MHz, CDCl3): d 1.38 (m, 47H, CH2, BOC-CH3), 1.83
(s, 4H), 2.20 (m, 14H, CH2COO), 3.17 (m, 14H, CH2N),
4.77 (br, 1H, NHBOC), 5.05 (m, 8H, CH2-Bn), 5.20 (m, 8H,
CH2-Bn), 5.74 (m, 10H, pCH), 5.89 (m, 4H, pCH), 6.50 (br,
4H, NH), 6.61 (br, 2H, NH), 7.07 (m, 12H, Ph), 7.14 (m, 8H,
q-Bn), 7.26 (m, 20H, Bn), 7.37 (m, 14H, Bz), 7.53 (m, 7H,
q-Bz), 7.90 (m, 8H, Bz), 8.01 (m, 6H, Bz); 13C NMR
(100.6 MHz, CDCl3): d 23.8, 23.9, 24.0, 24.2, 25.7, 25.8,
25.9 (CH2), 28.3 (BOC-CH3), 28.6, 28.7, 28.8, 29.4 (CH2),
32.9, 33.0, 33.4, 33.5, 33.6 (CH2COO), 38.9, 39.0, 39.2,
39.3 (CH2N), 67.7, 67.8 (CH2-Bn), 70.7, 71.1, 71.2, 72.3,
72.7, 72.9 (pCH), 78.9 (q-BOC), 128.2, 128.3, 128.4,
128.45, 128.5, 128.6, 128.7, 129.8, 129.9, 133.6, 133.8,
133.9, 134.4, 134.7 (Ph), 156.0 (BOC-CvO), 164.9,
164.97, 165.5, 165.6, 166.1, 171.9, 171.92, 172.0 (CvO);
MS (FAB): m/z (%): 3283 (1) [MþH]þ, 3183 (100)
[M2BOC]þ, 3093 (8) [M2BOC-Bn]þ, 1889 (10), 1313
(10); C180H191O52N7 (3284.3): calcd: C 65.81, H 5.87, N
2.99; found: C 65.36, H 5.88, N 2.67; UV/Vis (CH3CN)
lmax (1) (nm): 274, 268, 231 (83250); UV/Vis (CH3OH)
lmax (1) (nm): 268, 231 (81600); [a]2D0¼-12.5 (c¼0.8400,
CH2Cl2).
5.06 (d, J¼8 Hz, 4H, CH2-Bn), 5.72 (d, J¼4 Hz, 1 H,
2
3
pCH), 5.81 (d, J¼4 Hz, 1H, CH), 7.31 (m, 10H, Ph-Bn),
7.44 (m, 2H, Ph-Bz), 7.55 (m, 1H, Bz), 8.01 (m, 2H, Bz);
13C NMR (100.6 MHz, CDCl3): d 24.3, 24.4, 26.0, 26.1,
26.2 (CH2), 28.4 (BOC-CH3), 28.9, 29.0, 29.6, 29.6, 33.7,
33.9, 34.0, 39.3, 39.4, 40.3 (CH2), 66.1, 72.2, 72.8, 79.0
(q-BOC), 118.5, 128.2, 128.5, 128.6, 128.7, 129.9, 133.9,
136.0, 155.9 (BOC-CvO), 165.0, 166.1, 171.9, 173.1
(CvO); MS (FAB): m/z (%): 874 (40) [MþH]þ, 774
(100) [M2BOC]þ; C48H63O12N3 (874.0): calcd: C 65.96, H
7.27, N 4.81; found: C 65.56, H 6.88, N 4.77; UV/Vis
(CH3CN) lmax (1) (nm): 274, 268, 263, 231 (12900);
UV/Vis (CH3OH) lmax (1) (nm): 274, 268, 263, 231
(13000); [a]2D0¼-16.0 (c¼0.123, CH2Cl2).
3
p
4.5.20. Compound 23, model compound. Compound 23
was synthesized according to general procedure III with
compound 12 (604 mg; 1.29 mmol) and benzyl 6-amino-
hexanoate11 (1061 mg; 2.58 mmol). The crude product was
purified by column chromatography (silica, CH2Cl2/MeOH,
20:1; Rf¼0.36).
Yield 980 mg, 1.12 mmol, 87%, white solid. 1H NMR
(400 MHz, CDCl3): d 1.39 (m, 27H, BOC-CH3, CH2), 2.31
(m, 6H, CHCOO), 3.15 (m, 6H, CH2N), 4.65 (br, 1H, NH),
5.07 (d, 2J¼8 Hz, 4H, CH2-Bn), 5.73 (d, 3J¼4 Hz, 1H,
4.5.18. Compound 21, dendron third generation. Com-
pound 21 was synthesized according to general procedure
III with compound 18 (TFA adduct) (330 mg; 0.2 mmol)
and with compound 11 (47 mg; 0.1 mmol). The crude
product was purified by column chromatography (silica,
CH2Cl2/MeOH, 25:1; Rf¼0.12).
Yield 234 mg, 0.07 mmol, 71%, white solid. 1H NMR
(400 MHz, CDCl3): d 1.38 (m, 47H, CH2, BOC-CH3), 1.74
(s, 4H), 2.20 (m, 14H, CH2COO), 3.15 (m, 14H, CH2N),
4.77 (br, 1H, NHBOC), 5.15 (m, 16H, CH2-Bn), 5.71 (m,
4H, pCH), 5.78 (m, 8H, pCH), 5.83 (m, 4H, pCH), 6.50 (br,
6H, NH), 7.08 (m, 12H, Ph), 7.14 (m, 8H, q-Bn), 7.26 (m,
3
p
pCH), 5.81 (d, J¼4 Hz, 1H, CH), 7.32 (m, 10H, Ph-Bn),
7.41 (m, 2H, Ph-Bz), 7.55 (m, 1H, Bz), 8.01 (m, 2H, Bz);
13C NMR (100.6 MHz, CDCl3): d 24.3, 24.4, 24.9, 26.0,
26.1 (CH2), 28.4 (BOC-CH3), 28.9, 29.0, 29.5, 33.7, 33.9,
34.0, 39.2, 39.4, 40.3 (CH2), 66.1, 72.2, 72.8, 79.0 (q-BOC),
128.2, 128.5, 128.6, 128.7, 129.9, 133.9, 136.0, 155.9
(BOC-CvO), 165.0, 166.1, 171.9, 173.2 (CvO); MS
(FAB): m/z (%): 874 (40) [MþH]þ, 774 (100)
[M2BOC]þ; C48H63O12N3 (874.0): calcd: C 65.96, H
7.27, N 4.81; found: C 66.34, H 7.58, N 4.92; UV/Vis
(CH3CN) lmax (1) (nm): 274, 268, 263, 231 (12900);

B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
3913
UV/Vis (CH3OH) lmax (1) (nm): 274, 268, 263, 231
(13000); [a]2D0¼þ16.0 (c¼0.123, CH2Cl2).
by column chromatography (silica, CH2Cl2/MeOH, 30:1;
Rf¼0.11).
4.5.21. Compound 24, dendron first generation (anthra-
cene). Compound 24 was synthesized according to general
procedure III with compound 9 (TFA-adduct) (1.98 g;
3 mmol) and 9-anthracenecarboxylic acid (0.67 g;
3.0 mmol). The crude product was purified by column
chromatography (silica, EtAc/hexane, 1:2; Rf¼0.18).
Yield 210 mg, 0.13 mmol, 68%, white solid. 1H NMR
(500 MHz, CDCl3): d 1.40 (m, 20H, CH2), 2.10 (m, 4H,
CH2COO), 2.43 (m, 1H, CH2COO), 2.97 (m, 1H,
CH2COO), 3.15 (m, 6H, CH2N), 4.60 (br, 1H, NH), 5.15
p
(m, 8H, CH2-Bn), 5.80 (m, 6H, CH), 6.24 (br, 1H, NH),
6.45 (br, 1H, NH), 7.28 (m, 36H, Ph), 7.92 (m, 8H, Ph), 8.40
(s, 1H, Ph-anthracene); 13C NMR (125 MHz, CDCl3): d
23.9, 24.0, 24.2, 24.9, 25.5, 25.8, 25.9, 26.0, 28.7, 28.8,
28.9, 29.0, 29.1, 29.5 (CH2), 33.0, 33.1, 33.7, 33.9
(CH2COO), 38.9, 39.0, 39.2, 39.3, 39.5 (CH2N),67.6,
67.7, 67.8, 67.9, (CH2-Bn), 70.7, 70.8, 71.2, 71.7, 72.3,
72.7, (pCH), 125.1, 125.5, 126.7, 128.0, 128.1, 128.3, 128.4,
128.5, 128.6, 128.7, 129.0, 129.9, 130.1, 131.1, 132.2,
133.7, 133.9, 133.9, 134.5, 134.8, 134.9, 164.9, 165.1,
165.6, 165.7, 165.8, 165.9, 166.0, 166.1, 168.6, 169.3,
169.6, 171.9, 172.1, 172.2; MS (FAB): m/z (%): 1631 (12)
[MþH]þ, 205 (100); C94H91O23N3 (1630.7): calcd: C 69.23,
H 5.62, N 2.58; found: C 69.39, H 5.84, N 2.70; UV/Vis
(CH2Cl2) lmax (1) (nm): 382, 362, 345, 330, 253 (124000).
Yield 1.53 g, 2 mmol, 67%, yellow solid. 1H NMR
(400 MHz, CDCl3): d 1.47 (m, 2H, CH2), 1.65 (m, 4H,
3
CH2), 2.19 (quin, J¼7.2 Hz, 1H, CH2COO), 2.30 (quin,
3J¼7.2 Hz, 1H, CH2COO), 3.68 (m, 2H, CH2N), 4.75 (d,
2J¼12 Hz, 1H, CH2-Bn), 4.84 (d, 2J¼12 Hz, 1H, CH2-Bn),
2
2
5.05 (d, J¼12 Hz, 1H, CH2-Bn), 5.18 (d, J¼12 Hz, 1H,
3
p
3
CH2-Bn), 5.77 (d, J¼4 Hz, 1H, CH), 5.87 (d, J¼4 Hz,
1H, pCH), 6.24 (br, 1H, NH), 7.04 (m, 6H, Ph), 7.27 (m, 6H,
Ph), 7.40 (m, 5H, Ph), 7.92 (m, 6H, Ph), 8.40 (s, 1H, Ph); 13C
NMR (100.6 MHz, CDCl3): d 24.2, 26.1, 19.2, 33.3, 39.7
(CH2), 60.4, 67.7 (CH2-Bn), 70.7, 71.1 (pCH), 115.7, 122.8,
124.0, 125.0, 125.4, 125.6, 126.6, 126.8, 127.7, 127.7,
127.9, 128.0, 128.2, 128.3, 128.4, 128.5, 128.6, 128.9,
130.0, 131.0, 132.1, 133.7, 134.3, 134.7 (Ph, anthracene-
Ph), 164.9, 165.5, 165.6, 169.48, 172.0 (CvO); MS (FAB):
m/z (%): 752 (28) [MþH]þ, 661 (3) [M2Bn]þ, 205 (100)
[M2anthracene]þ; C46H41O9N (751.3): calcd: C 73.49, H
5.50, N 1.86; found: C 73.84, H 5.56, N 2.29; UV/Vis
(CH2Cl2) lmax (1) (nm): 384, 364, 347, 256 (124200).
4.5.24. Compound 27, dendron second generation
(anthracene). Compound 27 was synthesized according to
general procedure III with compound 17 (TFA adduct)
(278 mg; 0.17 mmol) and with 9-anthracenecarboxylic
acid (36 mg; 0.16 mmol). The crude product was purified
by column chromatography (silica, CH2Cl2/MeOH, 30:1;
Rf¼0.11).
4.5.22. Compound 25, dendron first generation (anthra-
cene). Compound 25 was synthesized according to general
procedure III with compound 10 (TFA-adduct) (416 mg;
0.63 mmol) and 9-anthracenecarboxylic acid (140 mg;
0.63 mmol). The crude product was purified by column
chromatography (silica, EtAc/hexane, 1:2; Rf¼0.18).
Yield 190 mg, 0.12 mmol, 69%, white solid. 1H NMR
(500 MHz, CDCl3): d 1.40 (m, 20H, CH2), 2.10 (m, 4H,
CH2COO), 2.42 (m, 1H, CH2COO), 2.98 (m, 1H,
CH2COO), 3.15 (m, 6H, CH2N), 4.60 (br, 1H, NH), 5.15
p
(m, 8H, CH2-Bn), 5.80 (m, 6H, CH), 6.26 (br, 1H, NH),
6.44 (br, 1H, NH), 7.28 (m, 36H, Ph), 7.92 (m, 8H, Ph), 8.40
(s, 1H, Ph-anthracene); 13C NMR (100.6 MHz, CDCl3): d
23.9, 24.2, 24.9, 25.5, 25.8, 25.9, 28.7, 28.8, 29.0, 29.1,
(CH2), 33.0, 33.1, 33.7, 33.9 (CH2COO), 38.9, 39.0, 39.5
(CH2N),67.6, 67.7, 67.8, 67.9, (CH2-Bn), 70.7, 71.1, 72.1,
72.3, 72.7, 73.3 (pCH), 125.1, 125.5, 126.7, 128.0, 128.1,
128.3, 128.4, 128.5, 128.6, 128.7, 129.0, 129.9, 130.1,
131.1, 132.2, 133.7, 133.8, 133.9, 134.5, 134.8, 134.9,
164.9, 165.1, 165.6, 165.7, 165.8, 165.9, 166.0, 166.1,
168.6, 169.3, 169.6, 171.9, 172.1, 172.2; MS (FAB): m/z
(%): 1631 (10) [MþH]þ, 205 (100); C94H91O23N3 (1630.7):
calcd: C 69.23, H 5.62, N 2.58; found: C 68.43, H 5.85, N
2.81; UV/Vis (CH2Cl2) lmax (1) (nm): 382, 362, 345, 330,
253 (124000).
Yield 340 g, 0.45 mmol, 72%, yellow solid. 1H NMR
(400 MHz, CDCl3): d 1.48 (m, 2H, CH2), 1.67 (m, 4H,
3
CH2), 2.20 (quin, J¼7.2 Hz, 1H, CH2COO), 2.30 (quin,
3J¼7.2 Hz, 1H, CH2COO), 3.69 (m, 2H, CH2N), 4.77 (d,
2J¼12 Hz, 1H, CH2-Bn), 4.85 (d, 2J¼12 Hz, 1H, CH2-Bn),
2
2
5.07 (d, J¼12 Hz, 1H, CH2-Bn), 5.19 (d, J¼12 Hz, 1H,
3
p
3
CH2-Bn), 5.77 (d, J¼4 Hz, 1H, CH), 5.86 (d, J¼4 Hz,
1H, pCH), 6.22 (br, 1H, NH), 7.05 (m, 6H, Ph), 7.26 (m, 6H,
Ph), 7.40 (m, 5H, Ph), 7.92 (m, 6H, Ph), 8.41 (s, 1H, Ph); 13C
NMR (100.6 MHz, CDCl3): d 24.2, 26.1, 29.2, 33.3, 39.7
(CH2), 60.4, 67.7 (CH2-Bn), 70.7, 71.1 (pCH), 115.8, 124.0,
125.0, 125.4, 125.6, 126.6, 126.7, 127.7, 127.8, 127.9,
128.0, 128.2, 128.4, 128.5, 128.8, 128.9, 130.0, 131.0,
132.1, 133.7, 134.3, 134.7 (Ph, anthracene-Ph), 164.9,
165.5, 165.6, 169.48, 172.0 (CvO); MS (FAB): m/z (%):
1505 (4) [2MþH]þ, 752 (98) [MþH]þ, 661 (9) [M2Bn]þ,
205 (100) [M2anthracene]þ; C46H41O9N (751.3): calcd: C
73.49, H 5.50, N 1.86; found: C 73.14, H 5.83, N 1.56;
UV/Vis (CH2Cl2) lmax (1) (nm): 384, 364, 347, 256
(124200).
4.5.25. Compound 28, dendron second generation
(anthracene). Compound 28 was synthesized according to
general procedure III with compound 18 (TFA adduct)
(377 mg; 0.23 mmol) and with 9-anthracenecarboxylic
acid (51 mg; 0.23 mmol). The crude product was purified
by column chromatography (silica, CH2Cl2/MeOH, 30:1;
Rf¼0.10).
Yield 220 mg, 0.13 mmol, 59%, white solid. 1H NMR
(400 MHz, CDCl3): d 1.40 (m, 20H, CH2), 2.10 (m, 4H,
CH2COO), 2.21 (m, 1H, CH2COO), 2.98 (m, 1H,
CH2COO), 3.15 (m, 6H, CH2N), 4.60 (br, 1H, NH), 5.15
4.5.23. Compound 26, dendron second generation
(anthracene). Compound 26 was synthesized according to
general procedure III with compound 16 (TFA adduct)
(292 mg; 0.19 mmol) and with 9-anthracenecarboxylic
acid (42 mg; 0.19 mmol). The crude product was purified

3914
B. Buschhaus et al. / Tetrahedron 59 (2003) 3899–3915
p
Diederich, F. Chem. Eur. J. 1998, 4, 1353. (f) Tomalia, D. A.;
Naylor, A. M.; Goddard, W. A., III. Angew. Chem. Int. Ed.
Engl. 1990, 102, 119.
(m, 8H, CH2-Bn), 5.80 (m, 6H, CH), 6.28 (br, 1H, NH),
6.58 (br, 1H, NH), 7.28 (m, 36H, Ph), 7.92 (m, 8H, Ph), 8.40
(s, 1H, Ph-anthracene); 13C NMR (125 MHz, CDCl3): d
23.9, 24.0, 24.2, 24.9, 25.5, 25.8, 25.9, 26.0, 28.7, 28.8,
28.9, 29.0, 29.1, 29.5 (CH2), 33.0, 33.1, 33.7, 33.9
(CH2COO), 38.9, 39.0, 39.2, 39.3, 39.5 (CH2N),67.6,
67.7, 67.8, 67.9, (CH2-Bn), 70.7, 70.8, 71.2, 71.7, 72.3,
72.7, (pCH), 125.0, 125.5, 126.6, 127.9, 128.1, 128.2, 128.4,
128.5, 129.9, 131.1, 132.1, 133.6, 133.9, 134.4, 134.7,
164.9, 165.5, 165.6, 165.7, 165.9, 166.0, 168.6, 169.3,
169.6, 171.9, 172.0; MS (FAB): m/z (%): 1631 (14)
[MþH]þ, 205 (100); C94H91O23N3 (1630.7): calcd: C
69.23, H 5.62, N 2.58; found: C 69.47, H 5.84, N 2.59;
UV/Vis (CH2Cl2) lmax (1) (nm): 382, 362, 345, 330, 253
(124000).
4. For reviews on chiral dendrimers see: (a) Seebach, D.;
Rheiner, P. B.; Greiveldinger, G.; Butz, T.; Sellner, H. Top.
Curr. Chem. 1998, 197, 125. (b) Peerlings, H. W. I.; Meijer,
E. W. Chem. Eur. J. 1997, 3, 1563. (c) Thomas, C. W.; Tor, Y.
Chirality 1998, 10, 53. (d) Chow, H. F.; Mong, T. K. K.;
Nongrum, M. F.; Wan, C. W. Tetrahedron 1998, 54, 8543.
5. (a) Kremers, J. A.; Meijer, E. W. J. Org. Chem. 1994, 59,
4262. (b) Seebach, D.; Lappiere, J. M.; Skobridis, K.;
Greiveldinger, G. Angew. Chem. Int. Ed. Engl. 1994, 33,
440. (c) Seebach, D.; Lapiere, J. M.; Greiveldinger, G.;
Skobridis, K. Helv. Chim. Acta 1994, 77, 1673. (d) Chow,
H. F.; Mak, C. C. Tetrahedron Lett. 1996, 37, 5935. (e) Chang,
H. T.; Chen, C. T.; Kondo, T.; Siuzdak, G.; Sharpless, K. B.
Angew. Chem. Int. Ed. Engl. 1996, 35, 182. (f) Ashton, P. R.;
Boyd, S. E.; Brown, C. L.; Nepogodiev, S. A.; Meijer, E. W.;
Stoddart, J. F. Chem. Eur. J. 1997, 3, 975. (g) Newkome, G. R.;
Lin, X.; Weis, C. D. Tetrahedron: Asymmetry 1991, 2, 957.
(h) Jansen, J. F. G. A.; Peerlings, H. W. I.; Brabander-van den
Berg, E. M. M.; Meijer, E. W. Science 1994, 266, 1226.
(i) Lindhorst, T. K.; Kieburg, C. Angew. Chem. Int. Ed. Engl.
1996, 35, 1935.
4.5.26. Compound 29, dendron third generation (anthra-
cene). Compound 29 was synthesized according to general
procedure III with compound 19 (TFA adduct) (130 mg;
0.04 mmol) and with 9-anthracenecarboxylic acid (8 mg;
0.04 mmol). The crude product was purified by column
chromatography (silica, CH2Cl2/MeOH, 15:1; Rf¼0.19).
Yield 64 mg, 0.019 mmol, 22%, white solid. 1H NMR
(400 MHz, CDCl3): d 1.40 (m, 20H, CH2), 2.15 (m, 14H,
CH2COO), 3.15 (m, 14H, CH2N), 4.60 (br, 1H, NH),
6. Bernreuther, A.; Schreiner, P.; Huffer, M. Analysis of Chiral
Organic Molecules; Walter de Gruyter: Berlin, 1995.
7. Recker, J.; Tomcik, D. J.; Parquette, J. R. J. Am. Chem. Soc.
2000, 122, 10298.
p
5.15 (m, 16H, CH2-Bn), 5.80 (m, 14H, CH), 6.45 (br, 6H,
NH), 7.28 (m, 72H, Ph), 7.92 (m, 16H, Ph), 8.40 (s, 1H,
Ph-anthracene); 13C NMR (100 MHz, CDCl3): d 23.0, 24.0,
24.9, 25.6, 25.8, 25.9, 26.1, 28.1, 28.8, 29.0, 29.1, 31.7,
32.0, 33.0, 33.1, 33.5, 33.9, 35.2, 36.9, 39.1, 39.2, 39.3,
39.7, 49.1, 50.3, 53.7, 54.7, 67.7, 67.8, 67.9, 70.7, 71.2,
72.1, 72.3, 72.4, 72.9, 125.0, 125.5, 126.6, 127.9, 128.3,
128.4, 128.6, 129.9, 130.0, 133.6, 133.9, 134.4, 134.5,
142.0, 156.6, 165.0, 165.5, 165.7, 166.0, 166.2, 166.0,
171.9, 172.1; MS (FAB): m/z (%): 3390 (5) [MþH]þ, 3185
[M2anthracene]þ (100); C190H191O51N7 (3388.6): calcd: C
67.35, H 5.68, N 2.89; found: C 67.49, H 5.38, N 2.80;
UV/Vis (CH2Cl2) lmax (1) (nm): 383, 362, 345, 330, 254
(125000).
8. (a) McElhanon, J. R.; McGrath, D. V. J. Am. Chem. Soc. 1998,
120, 1647. (b) McElhanon, J. R.; McGrath, D. V. J. Org.
Chem. 2000, 65, 3525. (c) Junge, D. M.; McGrath, D. V.
Tetrahedron Lett. 1998, 39, 1701. (d) Balasubramanian, R.;
Rao, P.; Maitra, U. Chem. Commun. 1999, 23, 2353. (e) Mak,
C. C.; Chow, H. F. J. Chem. Soc. Perkin Trans. 1 1997, 91.
(f) Mak, C. C.; Chow, H. F. Pure Appl. Chem. 1997, 69, 483.
(g) Mak, C. C.; Chow, H. F. Chem. Commun. 1996, 1185.
(h) Kress, J.; Rosner, A.; Hirsch, A. Chem. Eur. J. 2000, 6,
247. (i) Murer, P.; Seebach, D. Angew. Chem. Int. Ed. Engl.
1995, 34, 2116. (j) Murer, P.; Seebach, D. Helv. Chim. Acta
1998, 81, 603. (k) Cicchi, S.; Goti, A.; Rosini, C.; Brandi, A.
J. Org. Chem. 1998, 2591.
9. Schemjakin, M. Angew. Chem. 1960, 10, 342.
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10. (a) Hofle, G.; Steglich, W. Synthesis 1972, 619. (b) Neiss, B.;
Acknowledgements
Steglich, W. Angew. Chem. 1978, 90, 556.
11. Bodansky, M.; Bodansky, A. The Practice of Peptide
Synthesis; Springer: Berlin, 1994.
We thank the Deutsche Forschungsgemeinschaft for
financial support and Dr R. Waibel from the Institut fu¨r
12. Murer, P. K.; Lapierre, J. M.; Greiveldinger, G.; Seebach, D.
Helv. Chim. Acta 1997, 80, 1648.
¨
Pharmazie der Universitat Erlangen-Nurnberg for his help
during the measurements of the CD spectra.
¨
13. Greiveldinger, G.; Seebach, D. Helv. Chim. Acta 1999, 81,
1003.
14. Ashton, P. R.; Anderson, D. W.; Brown, C. L.; Shipway, A. N.;
Stoddart, J. F.; Stoddart, M. S.; Tolley, M. S. Chem Eur. J.
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