Aromatic δ-peptides: Design, synthesis and structural studies of helical, quinoline-derived oligoamide foldamers

Article abstract of DOI:10.1016/j.tet.2003.08.058

Oligoamides of 8-amino-4-isobutoxy-2-quinolinecarboxylic acid were designed and synthesized, and their helical structures were characterized in the solid state by single crystal X-ray diffraction, and in solution by ¹H NMR. The monomer methyl 4

Full text of DOI:10.1016/j.tet.2003.08.058

Tetrahedron 59 (2003) 8365–8374
Aromatic d-peptides: design, synthesis and structural studies
of helical, quinoline-derived oligoamide foldamers
a
Hua Jiang, Jean-Michel Leger, Christel Dolain, Philippe Guionneau and Ivan Huc
b
a
c
a
,
*
´
a
´
Institut Europeen de Chimie et Biologie, 16 av. Pey Berland, 33607 Pessac Cedex, France
b
´
Laboratoire de Pharmacochimie, Universite Victor Segalen Bordeaux II, 146 rue Leo Saignat, 33076 Bordeaux, France
Institut de Chimie de la Matiere Condensee de Bordeaux, 87 Avenue du Docteur Schweitzer, 33608 Pessac Cedex, France
´
c
`
´
Received 6 June 2003; revised 1 August 2003; accepted 29 August 2003
Abstract—Oligoamides of 8-amino-4-isobutoxy-2-quinolinecarboxylic acid were designed and synthesized, and their helical structures
1
were characterized in the solid state by single crystal X-ray diffraction, and in solution by H NMR. The monomer methyl 4-isobutoxy-8-
nitro-2-quinolinecarboxylate is easily prepared in three steps from 2-nitroaninile and dimethyl acetylene dicarboxylate. Successive
hydrogenations of nitro groups, saponifications of esters and couplings of amines and acids via the acid chlorides gave a dimer, tetramer,
hexamer, octamer, and decamer in a convergent fashion. The oligomers were shown to adopt a bent conformation stabilized by
intramolecular hydrogen bonds between amide hydrogens and adjacent quinoline nitrogens. In the solid, the dimer adopts a planar crescent
shape and the octamer a helical conformation. All NMR data are consistent with similar conformations in solution. The helices are apparently
remarkably stable. Some of them remain helical even at 1208C in deuterated DMSO. The structural studies confirm the predictions made by
computer and demonstrate the high potency of the design principles.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
zides.3–5 Several families of aromatic oligomers have also
been shown to adopt stable linear, bent, and helical
conformations that may prove useful in the field of
peptidomimetics.3,6–15 Among these, the aromatic struc-
tures which bear the strongest analogy with peptides are
oligoamides as well, the conformation of which can be
stabilized by hydrogen bonds between amide groups and
donors or acceptors belonging to the adjacent aromatic
rings. Several families of aromatic oligoamides have been
described based on various aromatic building blocks (e.g.
pyridines,6–9 anthranilic acids,6,7 pyridine oxides,6 pyra-
zines,10 1,3-dimethoxybenzenes7,11…). Some aromatic
oligomers have also been based on ureas12 or hydrazides13
instead of amide linkages, and others have been incorpor-
ated into aliphatic sequences in order to template their
structures.14 Overall, these aromatic oligomers have been
less studied than their aliphatic counter-parts despite the fact
their specific features should be very useful in the context of
applications.15 For example, they often exhibit high con-
formational stability and very strong resistance to hydroly-
sis (as aromatic amides in general), and most importantly
their structures can often be accurately predicted.
Numerous small and large peptides have biological
activities that could have useful therapeutic applications if
they were not readily degraded in vivo by proteases. For
many years, chemists have worked at the design of so called
peptidomimetics: protease resistant unnatural substances
mimicking the structures and potentially the functions of
peptides. Whilst initial studies were focused on analogues of
relatively small peptides, recent developments have demon-
strated that the folded secondary structures of large peptides
(e.g. a-helices or b-sheets, or b-turns) can also be mimicked
by unnatural oligomers. Such oligomers having predictable
and well-defined conformations in solution are termed
foldamers.1–3 They represent a significant step forward in
the field of peptidomimetics and, in the long run, may open
the door to fully synthetic analogues of proteins.
The most studied families of unnatural oligomers mimick-
ing the folded structures of a-peptides are aliphatic in
nature.2,3 They comprise b-, g-, and d-homologues of
peptides, assembled using various linkages such as amides,
sulfonamides, sulfoximine, N-oxo-amides, ureas, or hydra-
In the following, through the presentation of the synthesis
and structural studies of a new family of quinoline derived
oligomers,16 we aim to emphasize the efficiency and
generality of simple design principles of aromatic oligo-
amide foldamers.
Keywords: heterocycles; conformation analysis; helical structures;
hydrogen bonds; supramolecular chemistry.
*
Corresponding author. Tel.: þ33-540-00-22-19; fax: þ33-540-00-22-26;
e-mail: i.huc@iecb-polytechnique.u-bordeaux.fr
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.08.058

8366
H. Jiang et al. / Tetrahedron 59 (2003) 8365–8374
may be more bent and give rise to helices with approxi-
mately 3 units per turn (Fig. 1(f)). Quinoline monomer 1c
was designed for this purpose (Scheme 1). Its nitro and ester
groups can respectively, be reduced to an amine and
saponified to an acid, oriented at ,608. It possesses an
endocyclic nitrogen that should allow intramolecular
hydrogen bonding with adjacent amide hydrogens
(Fig. 1(d)), and the isobutoxy substituent in position 4 is
expected to diverge from the helix and tune its solubility.
Molecular modeling (see below) supports these predictions
and suggests a helical conformation for strands as short as a
trimer. Conversely, modeling shows that about 3.5 units
should be necessary to accomplish one turn using a similar
substitution motif, but when hydrogen bonds take place on
the outer rim (Fig. 1(e)).
Figure 1. Bending of aromatic oligomers depends on intramolecular
hydrogen bonds on the inner or outer rim of the oligomer, and on the
substitution motif (ortho, meta…) of aromatic rings.
3. Synthesis
The preparation of monomer 1c was easily carried out in
three steps (Scheme 1). As described in the literature,17 the
addition of 2-nitro-aniline to dimethyl acetylene dicarboxyl-
ate gives 1a which can be isolated by simple filtration (yield
.70%). An X-ray structure of this compound allowed to
assign a trans configuration of the double bond (Fig. 2). The
conversion of enamine 1a to quinolinone 1b can be carried
out either thermally (reflux of Ph2O) or in PPA (yield about
65%).17 The quinolinone tautomeric form of 1b in the solid
state was characterized by single crystal X-ray diffraction
(Fig. 2). The alkylation of the oxygen in position 4 was
achieved under Mitsunobu conditions in 90% yield. The
structure of the product was again validated by an X-ray
structure (Fig. 2). No trace of N-alkylation was detected in
this reaction. Hydrogenation and saponification of nitro-
ester 1c under standard conditions gave quantitative yields
of amino-ester 1d and nitro-acid 1e, respectively. The
activation of 1e proceeded smoothly in refluxing SOCl2 and
the subsequent reaction with 1d gave nitro-ester dimer 2a in
excellent yield.
2. Design of the structures
The predictability of the folding of an oligomeric molecule
is largely increased when stabilizing intramolecular inter-
actions (e.g. hydrogen bonds) take place between consecu-
tive units. The computational and/or experimental studies of
a simple dimer or trimer then provides accurate data on the
relative positioning of consecutive units that, in many cases,
may be extrapolated to longer oligomers. Good illustrations
of this strategy are oligoamides derived from pyridine
diamines and pyridine diacids (Fig. 1(a)),8,9 or those derived
from 4,6-dimethoxy-3-amino-benzoic acid (Fig. 1(b)).11
Short oligomers in these series adopt planar ‘crescent’
conformations stabilized by intramolecular hydrogen bonds
between consecutive units. Longer oligomers are bent in the
same way, and slightly deviate from planarity so as to form
helices. In contrast, the conformational study of a dimeric,
trimeric, or tetrameric a-peptide give little indication that
longer sequences may fold into an a-helix.
The pitch of aromatic oligoamide helical foldamers
typically corresponds to the thickness of one aromatic
ring. This parameter is fixed and does not allow to tune the
structures. On the other hand, the diameter of the helices and
the number of monomers per helical turn depend directly on
the relative positioning of consecutive units. In oligomers of
six-membered meta substituted aromatics, one expects an
angle of approximately 1208 between consecutive units
leading to about six units per helical turn (Fig. 1(c)). In
practice, intramolecular hydrogen bonding has an effect on
the bending of the strands. In the case of oligomers of
pyridine diamines and pyridine diacids (Fig. 1(a)), the
hydrogen bonds take place at the inner rim of the helices,
which pinches the strand and reduces the number of
monomer per turn to approximately 4.5. Conversely, when
the hydrogen bonds take place at the outer rim of the helices,
the bending of the strand is reduced and about 8 units are
necessary to accomplish one turn (Fig. 1(b)).
The hydrogenation, saponification, activation in SOCl2 and
coupling were applied successfully to dimer 2a to give
In any case, bending remains larger than in helices of
aliphatic a, b and g peptide for which 2 to 4 units per turn is
typical. We speculated that aromatic oligoamides with
substituents oriented at 608 (for example ortho substituents),
Scheme 1. Synthesis of quinoline monomers: (a) dimethylacetylene
dicarboxylate, MeOH, K; (b) PPA, 1208, or diphenyl ether, reflux;
(c) iBuOH, DIAD, PPh3, THF, rt; (d) H2–Pd/C, EtOAc, rt; (e) KOH,
THF–water 2:1 vol/vol.

H. Jiang et al. / Tetrahedron 59 (2003) 8365–8374
8367
Figure 2. Stick representations of the structures of 1a–1d in the crystal.
tetramer 4a, and again to tetramer 4a to give hexamer 6a
and octamer 8a (Scheme 2). When the reactions are
performed on larger scales, the yields tend to be higher.
The possibility to double the size of the oligomer at each
step, or ‘segment doubling strategy’,18 may lead very
effectively to long structures and high molecular weights.
However, we observed that the hydrogenation and the
saponification steps require increasing reaction times and/or
higher temperatures as the length of the oligomers increases.
This is presumably due to the folding of the structures in the
reaction mixtures, which hinder the reactive functions.
When the activation of octamer acid 8c and its coupling to
octamer amine 8b was attempted, only minor quantities of
hexadecamer were detected (,10%). This very low yield
may be attributed partly to the fact the reaction was
performed on a very small scale, and partly to a slow
reaction rate. Thus, the convergent synthesis of very long
strands will require some improvement, maybe using larger
scales, longer reaction times or higher temperatures.
In the meantime, we showed that long strands can be
prepared using an iterative approach. The coupling reactions
work well when one of the reagents has a folded structure
and the other is short and unhindered. For example, amine
8b reacts with the acid chloride of dimer 2c, to give decamer
10a (Scheme 2), which in turn may serve as a precursor of
a dodecamer and so on. Though less efficient than a
convergent segment doubling strategy, this iterative
approach should be useful to incorporate a series of different
monomers in a sequence, as in solid-phase peptide
synthesis.
Scheme 2. Synthesis of quinoline oligoamides. Hydrogenations and
saponifications are quantitative. Coupling yields range from 29 to 97%.
in the plane of the phenyl ring (torsion angle 26.18).
Interestingly, the carbonyl carbon nearest to the phenyl ring
is not the one involved in the electrophilic substitution
which gives 1b.
The structure of 1b is that of a 4-(1H)-quinolinone. The
electron density of a proton can be refined on the quinoline
nitrogen, and the C–O distance in position 4 is that of a
˚
˚
double bond (1.26 A, as opposed to 1.36 A in 1c and 1d). As
for compound 1a the proton in position 1 is involved in two
hydrogen bonds. A hydrogen bond with a nitro oxygen
19
˚
4. Solid state structural studies
(NH· · ·ON: 2.62 A, 129.58) defines a six-membered
hydrogen-bonded ring, and a hydrogen bond with the ester
19
˚
carbonyl oxygen (NH· · ·OvC: 2.66 A, 105.4) defines a
The solid state structures of precursors 1a and 1b, of
monomers 1c and 1d, of dimer 2a, and of octamer 8a16 were
all characterized by single crystal X-ray diffraction analysis.
The crystallographic data are summarized in Table 1. The
structures of 1a–1d give useful information about their
conformational and tautomeric preferences (Fig. 2). In
enamine 1a, the amine proton is involved in two hydrogen
bonds defining two six-membered hydrogen-bonded rings.
One hydrogen bond involves a nitro oxygen (NH· · ·ON:
five-membered hydrogen-bonded ring. The nitro group is in
the plane of the phenyl ring (torsion angle 3.68).
Compound 1c contains no hydrogen available for intra-
molecular hydrogen bonding. Its structure reveals the
repulsions between the different hydrogen bond acceptors
of the molecule. Because of the repulsion between the
quinoline oxygen and the nitro oxygens, the nitro group is
found almost perpendicular to the aromatic ring (torsion
angle of 9486). The ester group remains in the plane of the
19
˚
2.64 A, 142.68) and the other a carbonyl oxygen
19
˚
(NH· · ·OvC: 2.73 A, 124.78). The nitro group is almost

8368
H. Jiang et al. / Tetrahedron 59 (2003) 8365–8374
Table 1. Crystallographic parameters for the structures determined by X-ray diffraction analysis
Compound
1a
1b
1c
1d
2a
Mw
C12H12N2O6
CHCl3/n-hexane
0.40£0.40£0.15
Yellow
Cu Ka
Monoclinic
P21/n
9.299(4)
10.495(3)
13.640(3)
97.07(3)
1321.0(7)
4
280.24
1.409
5.33#u#64.86
2222/2222
182
1.074
6.2
211432
C11H8N2O5
Toluene/n-hexane
0.30£0.15£0.10
Yellow
Cu Ka
Monoclinic
P21/n
11.1580(10)
5.3940(10)
17.559(2)
93.08(10)
1055.3(2)
4
248.19
1.562
4.59#u#59.92
1528/1528
164
1.123
4.1
211434
C15H16N2O5
Toluene/n-hexane
0.25£0.32£0.50
Yellow
Cu Ka
Orthorombic
Pna21
10.012(1)
22.741(4)
6.875(1)
90
1565.3(4)
4
304.30
C15H18N2O3
Toluene/air
0.35£0.35£0.25
Colorless
Cu Ka
C29H30N4O7
Nitrobenzene/n-hexane
0.45£0.45£0.40
Yellow
Mo Ka
Monoclinic
P21/n
10.497(1)
21.402(1)
12.295(1)
92.68(1)
2759.1(4)
4
546.57
1.316
3.23#u#27.46
15357/5997
362
1.042
6.99
211433
Crystallizing solvent/precipitant
Crystal dimensions (mm)
Color
Radiation type
Unit cell
Monoclinic
P21/c
Space group
˚
a (A)
˚
7.713(1)
10.589(4)
17.822(1)
102.16(3)
1422.9(6)
4
274.31
1.280
6.58#u#64.94
2408/2408
182
b (A)
˚
c (A)
b (8)
V (A
3)
˚
Z
FW (g mol21
)
r (g cm23
Scanned u
)
1.291
4.83#u#64.89
1428/1428
191
1.017
8.15
211436
Total/unique refl.
Parameters
GOF
R1 (%)
CCDC Ref.
1.182
5.47
211435
aromatic ring, but the carbonyl is pointing away from
the quinoline nitrogen. This structure also reveals that the
carbon of the CH2 group of the isobutoxy moiety is in the
plane of the quinoline ring, anti to C(10) and syn to C(3).
This conformation is conserved in all 4-isobutoxy quino-
lines we have characterized in the solid state. It is
presumably due to steric repulsions between the CH2
protons and the proton in position 5 of the quinoline.
The bending of dimer 2a allows us to speculate that a trimer
cannot adopt a fully planar conformation, and that a steric
clash between the extremities of the strand will force a
torsion into a right handed or a left handed helix. This was
confirmed by the X-ray structure of 8a (Fig. 4)16 which
shows a helix extending to more than three turns. The third
unit in the octamer indeed overlaps with the first one. The
pitch of the helix is identical to the pitch of other helical
aromatic oligoamides and corresponds to the thickness of
˚
The X-ray structure of 1d shows that the amino group,
unlike the nitro group from which it is derived, lies in the
plane of the aromatic ring, forming a hydrogen bond with
one aromatic ring (3.4 A). The inner rim of the helix
accomplishes approximately one turn every 15 main chain
atoms and adopts a conformation similar to that of a
pentaaza-15-crown-5 macrocycle, with alternating amido
and pyrido nitrogens. Thus, almost exactly five units are
required for two helical turns (equivalent to 30 atoms of the
inner rim), which corresponds to the highest curvature
reached by helical aromatic oligoamides until now. Conse-
quently, helices of quinoline derived 4a–10a also have the
largest length per number of units: the helix of 8a is about
˚
the quinoline nitrogen (NH· · ·N: 2.69 A, 104.08). As shown
in Figure 3, the same hydrogen bond is present in the
˚
structure of dimer 2a (NH· · ·N: 2.69 A, 108.48). The amide
proton is also hydrogen bonded to the other quinoline
˚
nitrogen (NH· · ·N: 2.72 A, 126.58). These two hydrogen
bonds set the relative orientation of the quinoline rings in a
crescent conformation, as expected initially. The torsion
angles within the backbone of the molecule are all inferior
to 48, indicating that aromatic and amide moieties are
almost perfectly coplanar. The nitro and ester groups
slightly deviate from this plane.
˚
˚
13 A long, compared to 6.8 A for octamers of pyridine
oligoamides. The amido protons fill the helix hollow, and
completely prevent penetration of solvent molecules. As in
the dimer, amide protons are all involved in two hydrogen
bonds with the adjacent quinoline nitrogens that set the
orientation of the amido and quinoline moieties (Fig. 1). The
relative inclination of consecutive units can be estimated
from the torsion angles between the N(1)–C(2) bond of a
quinoline and the C(8)–C(9) of the next quinoline which
range from 159.2 to 169.58. The isobutyl chains adopt
various conformations, but the position of the CH2 carbon
is always the one found in the monomers 1c and 1d. The
core of the helix has a very regular structure, illustrated
by almost constant distances between the oxygens in
˚
position 4 of the quinolines (from 11.87 to 11.93 A).
Bending is even along the strand and does not depend upon
the central or terminal position of the units, or the
conformation of the side chain or interactions associated
with crystal packing.
The principles used to design the folded conformation of
Figure 3. Front view and side view of the structure of 2a in the crystal.

H. Jiang et al. / Tetrahedron 59 (2003) 8365–8374
8369
Figure 5. Superposition of part of the structure of 2a in the crystal and the
N-terminal fragment of the structure of 8a in the crystal. In 2a, the dihedral
angles of the linkages between the amide and both quinoline rings have
been changed so as to match those of 8a.
Figure 4. Crystal structure of 8a. Included solvent molecules, hydrogens,
and isobutyl chains have been omitted for clarity. (a) Side view and top
view of the entire structure; (b) fragments showing the relative positioning
of quinoline rings (in black) above and below a quinoline dimer within the
helix. The direction of these views is perpendicular to the planes of
the aromatic rings, and not exactly parallel to the helix axis. Consequently,
the two quinolines in black appear as off-set whislt they are almost
superimposed in the structure.
5. Solution studies
Solution studies were performed to assess whether the
folded structures observed in the solid state are also
1
prominent in solution. The H NMR spectra of 2a–10a in
CDCl3 are sharp (Fig. 7) and show no indication of
hybridization into double helices or other types of
aggregates, as was observed for pyridine derived oligo-
amides.9 The signals are spread over a remarkably large
range of chemical shifts despite the repetitive nature of the
sequences, suggesting different environments of the units.
Amide protons are deshielded at 10–12.5 ppm, as expected
for a hydrogen-bonded structure. Increasing strand length
results in a strong shielding of aromatic, amide and ester
protons that can be attributed to tight contacts between
aromatic rings. For example, the signal of the ester CH3
shifts from 4.23 ppm in 2a to 2.93 ppm in 10a (Fig. 7), and
the singlets assigned to the protons in position 3 of the
quinoline are found between 7.63 and 8.01 ppm in 2a, and
between 6.05 and 6.96 ppm in 10a. On the other hand, the
chemical shifts of the isobutyl residues are relatively
independent from oligomer length.
these oligomers are essentially based on the hydrogen bonds
between consecutive units within the sequence. However,
the solid state structure shows extensive aromatic overlap
which probably plays an important role in the stabilization
of the helix. As shown in Figure 4(b), a given quinoline in
the helix does not have the same position with respect to the
aromatic rings above it and below it. Computational
methods may provide an estimate of the strength of
interactions between these stacked aromatics. But a simple
comparison of the structure of 8a, where intramolecular
aromatic stacking is extensive, and of 2a, where there is no
intramolecular stacking, already provides useful infor-
mation. As shown in Figure 5, the structure of 2a matches
very well with the N-terminal fragment of the structure of
8a. This suggests that the curvature of the strands is
essentially determined by the hydrogen-bonds. Intra-
molecular aromatic stacking in 8a either happens to be
optimum in the position set by hydrogen-bonding, or
provides too small a gain in interaction energy to perturb
the hydrogen bonds and force the curvature to change to the
position where it is most favorable. Thus, the fact that we
neglect aromatic stacking apparently has little consequence
on the accuracy of the design. In oligoamide aromatic
foldamers, it may in principle be possible to study a simple
dimer and extrapolate its structure to predict the helix
formed by a longer oligomer.
The UV–vis absorption spectra of 2a–10a show batho-
chromic and hypochromic effects with increasing oligomer
length which also suggest intramolecular p-stacking in
solution. The spectrum of 2a is characterized by an
absorption maximum at 245 nm (1¼40400 mol21 L cm21),
and by a broad series of less intense bands from 300 to
430 nm (1<12000 mol21 L cm21). As the strands become
longer, these absorption maxima are red-shifted up to
Dl¼8 nm, and the molar extinction coefficients ‘per
The crystal structure of 8a also allows us to rate the quality
of the prediction made by very simple molecular modeling
methods. Figure 6 shows the superposition of the helix of 8a
in the solid state, and the helix predicted for 8a by an energy
minimization using the MM3 force field in Macromodel,
without changing anything to the set of parameters
available. A side view of the helix shows an almost perfect
prediction of its diameter and of its pitch. Top views show
that when the N-terminal regions are docked so as to match,
Figure 6. Superposition of the structures of 8a in the crystal and obtained
from a simple energy minimization (MM3 force field in Macromodel).
(a) Side view of the helix; (b) top view of the N-terminal fragments which
were positioned so as to result in the best match; (c) superposition of the
˚
the C-terminal regions are offset by less than 3 A after three
helical turns. This indicates that the prediction of the
curvature of the helix (the number of units per turn) is not
perfect, but that the error remains below 5%.
˚
C-terminal fragments which show an offset of about 3 A of the helices.

8370
H. Jiang et al. / Tetrahedron 59 (2003) 8365–8374
Figure 7. Part of the 1H 400 MHz NMR spectra of: (a) 2a; (b) 4a; (c) 6a; (d) 8a; and (e) 10a in CDCl3.
quinoline ring’ drop by 20–25%. In all these oligomers, the
fluorescence of the quinolines is quenched, presumably by
the nitro groups.
signals of diastereotopic protons are similar to those of 4a in
CDCl3, and despite the fact that DMSO should compete
with intramolecular hydrogen bonding and destabilize the
helices to some extent.
Upon adding chiral shift reagent Eu(hfc)3 to a CDCl3
1
solution of 8a, amide, aromatic and ester H NMR signals
These data are similar to the data obtained for oligoamides
of 2,6-pyridinedicarboxylic acids and 2,6-diaminopyridines.
They are consistent with helical structures of 4a, 6a, 8a and
10a in solution, but do not fully demonstrate that the
solution conformations are identical to those observed in the
solid state. ROESY experiments on 8a show correlations
between protons in position 3 of the quinolines and protons
in position 5 and 7. We expect that these correlations will
give direct evidence of a helical structure in solution but
we have failed up to now in assigning these signals
unambiguously to the corresponding quinoline rings in the
sequence. The NMR techniques developed for solving the
solution structures of a-peptides have been applied to
aliphatic b- and g-peptides but are not directly applicable to
aromatic compounds.20 In particular, the string of spin
systems on the sequence cannot be reconstituted solely from
correlations between protons, and requires the assignment
of a large part of the 13C NMR spectrum. We are currently
working on NMR protocols that should allow complete
assignment and solution of the structure of aromatic amide
oligomers.
split into two signals of equal intensities, suggesting that
this compound exists as a mixture of enantiomers, and that
stereoselective interactions with Eu(hfc)3 do not induce an
enantiomeric excess. This is also supported by the pattern of
the signals of the OCH2 groups at 3.4–4.4 ppm. In the
absence of Eu(hfc)3, these signals appear as sharp doublets
in 2a and as diastereotopic motifs in 6a, 8a, and 10a. For
tetramer 4a, three OCH2 doublets are seen along with a
broad signal. Upon heating this broad signal sharpens into a
doublet, and upon cooling, all signals coalesce before
sharpening into doublets of doublets (Fig. 8). This
compound adopts a chiral conformation as well, but its
inversion is faster. For comparison, inversions of 8a and 6a
are slow even at high temperatures in polar solvents. For
example no coalescence is observed at 1208C in D6-DMSO
(!) although the chemical shift differences between the
Assuming that the helices in solution are indeed like the
helix observed in the solid state by single crystal X-ray
diffraction, the relative rates of helix inversion of 4a, 6a,
and 8a are particularly remarkable. The temperature of
coalescence of the signals of the diastereotopic CH2 protons
is below 258C for 4a, and well above 1208C for 6a and 8a,
since at that temperature, the signals are barely broader than
at 258C. This implies that the helical shape is almost fully
conserved even at high temperature and suggests that the
helices of 6a–10a are considerably more stable than most, if
not all, folded helical oligomers of similar lengths reported
up to now.
Figure 8. Part of the 1H 400 MHz NMR spectra of 4a in CDCl3 at various
temperatures showing the emergence of diastereotopic patterns in the
signals of CH2 groups.

H. Jiang et al. / Tetrahedron 59 (2003) 8365–8374
8371
Because 4a is shorter than two turns, its inversion can, in
principle, proceed through a rotation of ca. 3308 about a
single bond connected to the central amide group. The
activation of this process requires the disruption of a single
hydrogen bond, and of all intramolecular p–p contacts. On
the other hand, oligomer 6a is longer than two turns. Its
inversion requires at least two simultaneous 3308 rotations.
The activation of this process thus requires the disruption of
two hydrogen bonds and of all intramolecular p–p
contacts. Although the length of 4a and 6a differ by only
30%, a significant difference in rates of inversion may
indeed be expected, especially if intramolecular p–p
stacking is cooperative. For strands longer than two turns
(e.g. 8a and 10a), the inversion may proceed upon
propagating along the structure a 5 or 6 units long unfolded
segment connecting a stretch of right handed helix to a
stretch of left handed helix. The formation and propagation
of such a segment requires the simultaneous disruption of
not more than two hydrogen bonds and of p–p stacking
over not more than two helical turns.21 Thus, the activation
energy of helix inversion is not expected to increase as
rapidly with strand length as if a full unfolding were
necessary.
phosphine (2.25 g, 1.05 equiv.), 2-methyl-1-propanol
(0.82 mL, 1.1 equiv.) and anhydrous THF (20 mL) under
Argon, was cooled down to 08C. Diisopropyl
azodicarboxylate (1.71 mL, 1.05 equiv.) was added and
the mixture was stirred at 08C for 30 min, then at room
temperature for 2 h. The solvent was evaporated and the
product was purified by flash chromatography (SiO2)
eluting with CH2Cl2. Yield 2.25 g (92%) of a yellow
1
solid. Mp: 174–1758C. H NMR (CDCl3) d 8.47 (1H, dd,
J¼1.3, 6.7 Hz), 8.10 (1H, dd, J¼1.3, 6.0 Hz), 7.63 (2H, m),
4.10 (2H, d, J¼12.4 Hz), 4.04 (3H, s), 2.29 (1H, m), 1.14
(6H, d, J¼6.7 Hz). 13C NMR (CDCl3) d 165.62, 162.70,
151.22, 148.26, 139.94, 126.31, 125.87, 125.05, 123.24,
102.13, 75.56, 53.31, 28.05, 19.11. IR (KBr) n, (cm21
)
2963, 1721, 1591, 1568, 1533, 1471, 1441, 1424, 1366,
1329, 1269, 1244, 1124, 1016, 866, 787, 760. TOF-MS m/z:
305.19 [M]þ, 327.15 [MþNa]þ, 343.12 [MþK]þ.
7.1.2. Synthesis of amines 1d, 2b, 4b, 8b. General
procedure for the hydrogenation of nitro groups. A
mixture of the nitro precursor 1c, 2a, 4a or 8a (e.g. 8 mmol)
dissolved in EtOAC (50 mL) and 10% Pd/C (0.29 g) was
stirred at ambient temperature under a 4 bar atmosphere of
hydrogen for 4 h. The solution was filtered through Celite,
and the solvent was evaporated. The product was charac-
1
terized by H NMR and used without further purification.
6. Conclusion
Methyl 4-isobutoxy-8-aminoquinoline-2-carboxylate 1d.
1
Quantitative yield. Yellow solid. H NMR (CDCl3) d 7.53
(1H, m), 7.48 (1H, s), 7.37 (1H, m), 6.95 (2H, dd, J¼6.0,
1.3 Hz), 5.10 (2H, broad s), 4.02 (3H, m), 4.00 (2H, s), 2.27
(1H, m), 1.14 (3H, s), 1.12 (3H, s).
In summary, we have shown that very simple principles may
allow the accurate design and prediction of the folding of
oligomeric strands into stable helical structures. When the
interactions, which stabilize the folded state occur between
consecutive units, even an isolated dimer exhibits the
pattern that leads to folding. The helical motif may be
obtained by simply extrapolating the bent conformation of
the shorter strands. The quinoline amino acid monomers we
have presented are easily accessible, functionalizable, and
assembled into oligoamides. These oligomers adopt
unusually stable helical conformations even in polar
solvents at high temperature. It seems reasonable to predict
that water soluble versions of these oligomers (e.g. bearing
polar groups in position 4) should fold just as well in
aqueous medium. Such stable structures may represent
attractive building blocks to elaborate synthetic mimics of
tertiary structural motifs of proteins. Progress is currently
made along these lines, and in the control of the helical
handedness of these molecules.
Dimer amine 2b from nitro 2a. Quantitative yield. Yellow
solid. 1H NMR (CDCl3) d 12.70 (1H, s), 9.04 (1H, m), 7.95
(1H, m), 7.76 (1H, s), 7.67 (1H, t, J¼8 Hz), 7.56 (2H, m),
7.38 (1H, t, J¼8 Hz), 7.02 (1H, m), 5.53 (2H, br), 4.10 (3H,
s), 4.09 (2H, d, J¼6.8 Hz), 4.06 (2H, d, J¼6.8 Hz), 2.30
(2H, m), 1.16 (12H, m).
Tetramer amine 4b from nitro 4a. The temperature was
raised to 508C and the reaction time increased to 60 h.
Quantitative yield. Yellow solid. 1H NMR (CDCl3) d 12.44
(1H, s), 11.94 (1H, s), 11.81 (1H, s), 9.05 (1H, d, J¼6.8 Hz),
8.43 (1H, d, J¼7.2 Hz), 8.01 (3H, m), 7.87 (1H, d, J¼8 Hz),
7.75 (1H, s), 7.73 (1H, t, J¼8 Hz),7.64 (1H, t, J¼8 Hz), 7.55
(1H, d, J¼8 Hz), 7.32 (1H, s), 7.27 (1H, t, J¼8 Hz), 7.02
(1H, t, J¼8 Hz), 6.92 (1H, s), 6.68 (1H, s), 5.97 (1H, d,
J¼8.8 Hz), 4.19 (4H, m), 3.91 (2H, d, J¼6.8 Hz), 3.87 (2H,
d, J¼6.8 Hz), 3.78 (2H, br), 3.52 (3H, s), 2.44 (2H, m), 2.33
(2H, m), 1.23 (24H, m).
7. Experimental
7.1. General
Octamer amine 8b from nitro 8a. The temperature was
raised to 508C and the reaction time increased to 60 h.
Quantitative yield. Yellow solid. 1H NMR (CDCl3) d 11.56
(1H, s), 11.43 (1H, s), 11.34 (1H, s), 11.17 (1H, s), 11.08
(1H, s), 11.00 (1H, s), 10.93 (1H, s), 8.25 (1H, d, J¼7.4 Hz),
8.12 (4H, m), 8.07 (1H, d, J¼8.0 Hz), 7.89 (3H, m), 7.83
(1H, d, J¼7.4 Hz), 7.73 (4H, m), 7.65 (1H, d, J¼7.4 Hz),
7.45 (1H, t, J¼8.0 Hz), 7.38 (1H, t, J¼8.0 Hz), 7.30 (4H,
m), 7.20 (1H, t, J¼8.0 Hz), 6.99 (1H, t, J¼8.0 Hz), 6.94
(1H, s), 6.88 (1H, s), 6.79 (1H, t, J¼8.0 Hz), 6.68 (1H, s),
6.64 (1H, s), 6.53 (2H, s), 6.38 (1H, s), 6.18 (1H, s), 5.68
Solvents (THF, toluene, CH2Cl2) were dried by filtration
over activated alumina on a commercially available setup.
FTIR spectra were recorded on a Brucker IFS 55 FT-IR
Spectrometer. 400 MHz 1H and 100 MHz 13C NMR spectra
were recorded on a Brucker 400 Ultrashield spectrometer.
The following notations are used for the H NMR spectral
splitting patterns: singlet (s), doublet (d), triplet (t),
multiplet (m), broad (br). Melting points are uncorrected.
1
7.1.1. Methyl 4-isobutoxy-8-nitroquinoline-2-carboxy-
late 1c. A mixture of 1b17 (2 g, 8 mmol) and triphenyl-

8372
H. Jiang et al. / Tetrahedron 59 (2003) 8365–8374
(1H, d, J¼7.4 Hz), 4.13 (4H, m), 3.99 (4H, m), 3.85 (5H,
m), 3.68 (2H, d, J¼6.0 Hz), 3.61 (1H, m), 3.13 (2H, s), 3.01
(3H, s), 2.51 (2H, m), 2.31 (5H, m), 2.19 (1H, m), 1.36 (9H,
m), 1.25 (30H, m), 1.11 (9H, m).
anhydrous CH2Cl2 (5 mL), and added over a period of
10 min to a solution of amine 1d, 2b, 4b, or 8b (0.95 equiv.)
and diisopropylethylamine (5.5 equiv.) in CH2Cl2 (10 mL)
at 08C. The reaction mixture was allowed to warm to room
temperature and stirred overnight. The solvent was removed
and the residue was purified by flash chromatography on
silica gel eluting with EtOAc–toluene, from 2:98 to 10:90
vol/vol, to afford the pure product.
7.1.3. Synthesis of 1e, 2c, 4c, 8c. General method for the
saponification of methyl esters. The methyl ester 1c, 2a,
4a, or 8a (e.g. 8 mmol) was dissolved in a mixture of THF
(100 mL) and methanol (50 mL). KOH (2.5 equiv.) was
added, and the solution was stirred at ambient temperature
for 20 h. The solution was neutralized using excess AcOH
and the product was extracted in dichloromethane
(3£50 mL). The organic phase was washed with water,
dried (MgSO4) and evaporated to give a yellow solid which
Dimer 2a, from acid 1e (1.5 g) and amine 1d (1.44 g). Yield
.96%. Yellow solid. Mp: 200–2018C. 1H NMR (CDCl3) d
11.88 (1H, s), 9.10 (1H, dd, J¼1.3, 6.7 Hz), 8.54 (1H, dd,
J¼1.3, 6.7 Hz), 8.21 (1H, dd, J¼1.3, 6.7 Hz), 8.01 (1H, m),
7.96 (1H, s), 7.63 (3H, m), 4.23 (3H, s), 4.18 (2H, d,
J¼6.7 Hz), 4.08 (2H, d, J¼6.7 Hz), 2.32 (2H, m), 1.16
(12H, m). 13C NMR (CDCl3) d 166.89, 163.16, 162.71,
162.45, 153.93, 148.32, 147.80, 139.69, 139.34, 134.85,
127.78, 126.63, 125.37, 123.39, 122.25, 118.71, 116.65,
101.45, 100.23, 75.67, 75.14, 53.61, 28.16, 28.08, 19.21,
19.15. IR (KBr) n, (cm21) 1718, 1671, 1593, 1567, 1522,
1418, 1341, 1109, 1038, 876, 749. TOF-MS m/z: 547.20
[M]þ, 569.16 [MþNa]þ, 585.13 [MþK]þ.
1
was characterized by H NMR and used without further
purification.
4-Isobutoxy-8-nitroquinoline-2-carboxyl acid 1e, from ester
1c (2.44 g). Quantitative yield. Yellow solid. 1H NMR
(CDCl3) d 8.56 (1H, dd, J¼1.3, 6.0 Hz), 8.24 (1H, dd,
J¼1.3, 6.7 Hz), 7.74 (2H, m), 4.15 (2H, d, J¼6.0 Hz), 2.33
(1H, m), 1.17 (3H, s), 1.15 (3H, s).
Dimer acid 2c from ester 2a. The reaction mixture was
stirred at ambient temperature for 2 h. Quantitative yield.
Yellow solid. H NMR (CDCl3) d 11.72 (1H, s), 9.17 (1H,
m), 8.56 (1H, d, J¼8 Hz), 8.28 (1H, d, J¼8 Hz), 8.08 (1H, d,
J¼8.8 Hz), 7.93 (1H, s), 7.79 (1H, s), 7.70 (2H, m), 4.19
(2H, d, J¼6.4 Hz), 4.13 (2H, d, J¼6.4 Hz), 2.32 (2H, m),
1.18 (3H, s), 1.17 (3H, s), 1.16 (3H, s), 1.15 (3H, s).
Tetramer 4a, from acid 2c (0.6 g) and amine 2b (0.49 g).
Yield 0.95 g (97%). Yellow solid. Mp: 208–2108C. 1H
NMR (CDCl3) d 12.30 (1H, s), 11.91 (1H, s), 11.68 (1H, s),
9.16 (1H, d, J¼6.7 Hz), 8.58 (1H, d, J¼6.7 Hz), 8.38 (1H, d,
J¼7.4 Hz), 8.15 (1H, d, J¼6.7 Hz), 8.02 (2H, m), 7.93 (1H,
d, J¼7.4 Hz), 7.86 (1H, s), 7.76 (1H, t, J¼8.0 Hz), 7.60 (2H,
m), 7.47 (1H, s), 7.39 (1H, t, J¼8.0 Hz), 7.27 (1H, t,
J¼8.0 Hz), 6.88 (1H, s), 6.69 (1H, s), 4.27 (2H, br), 4.20
(2H, d, J¼6.7 Hz), 3.91 (2H, d, J¼6.7 Hz), 3.85 (2H, d,
J¼6.7 Hz), 3.46 (3H, s), 2.49 (1H, m), 2.42 (1H, m), 2.32
(2H, m), 1.29 (3H, s), 1.28 (3H, s), 1.24 (3H, s), 1.22 (3H, s),
1.21 (3H, s), 1.19 (3H, s), 1.18 (3H, s). 13C NMR (CDCl3) d
164.36, 163.86, 163.54, 163.38, 162.71, 162.00, 161.04,
153.97, 151.47, 149.42, 146.01, 145.60, 139.61, 139.45,
138.61, 135.60, 134.43, 134.20, 128.47, 128.32, 127.72,
127.16, 126.33, 124.66, 124.22, 122.48, 122.37, 122.30,
118.13, 117.36, 117.13, 116.95, 116.56, 116.36, 100.93,
100.59, 99.21, 98.00, 76.15, 75.89, 75.58, 75.41, 52.79,
28.62, 28.54, 19.72. IR (KBr) n, (cm21) 2959, 1740, 1681,
1590, 1536, 1469, 1420, 1356, 1330, 1266, 1217, 1116,
1051, 877, 762. TOF-MS m/z: 1031.39 [M]þ, 1053.37
[MþNa]þ, 1069.34 [MþK]þ.
1
Tetramer acid 4c from ester 4a. The proportion of THF and
methanol was adjusted to 9:1 vol/vol and the reaction
mixture was stirred at 408C for 2 h. Quantitative yield.
Yellow solid. 1H NMR (CDCl3) d 12.12 (1H, s), 11.66 (1H,
s), 11.39 (1H, s), 9.15 (1H, d, J¼6.8 Hz), 8.56 (1H, d, J¼
8 Hz), 8.47 (1H, d, J¼7.2 Hz), 8.14 (1H, d, J¼7.2 Hz), 8.10
(1H, d, J¼7.2 Hz), 8.02 (1H, d, J¼8.8 Hz), 7.99 (1H, d,
J¼8 Hz), 7.95 (1H, s), 7.77 (1H, t, J¼8 Hz), 7.63 (2H, m),
7.41 (2H, m), 7.29 (1H, t, J¼8 Hz), 6.91 (1H, s), 6.77 (1H,
s), 4.26 (4H, br), 3.91 (4H, m), 2.43 (4H, m),1.21 (24H, m).
Octamer acid 8c from ester 8a. The proportion of THF and
methanol was adjusted to 9:1 vol/vol and the reaction
mixture was stirred at 408C for 8 h. Quantitative yield.
Yellow solid. 1H NMR (CDCl3) d 11.29 (1H, s), 11.17 (1H,
s), 11.07 (1H, s), 10.99 (1H, s), 10.96 (1H, s), 10.95 (1H, s),
10.83 (1H, s), 8.32 (1H, d, J¼8 Hz), 8.20 (2H, d, J¼7.4 Hz),
8.16 (2H, m), 8.13 (1H, d, J¼8.7 Hz), 8.05 (1H, d, J¼
7.4 Hz), 7.88 (3H, t, J¼8.7 Hz), 7.80 (2H, d, J¼8.0 Hz),
7.66 (1H, d, J¼8.0 Hz), 7.52 (1H, d, J¼8.0 Hz), 7.42 (2H,
m), 7.31 (4H, m), 7.15 (3H, m), 7.05 (1H, s), 7.01 (2H, m),
6.79 (1H, s), 6.66 (1H, s), 6.52 (1H, s), 6.47 (1H, s), 6.44
(1H, s), 6.15 (1H, s), 4.07 (3H, m), 3.89 (10H, m), 3.75 (2H,
d, J¼6.7 Hz), 3.65 (1H, t, J¼7.4 Hz) 2.50 (3H, m), 2.32
(13H, m), 1.35 (8H, m), 1.20 (40H, m).
Hexamer 6a, from acid 2c (0.26 g) and amine 4b (0.22 g).
Yield 0.27 g, (80%) (based on amine). Yellow solid. Mp:
1
.2508C. H NMR (CDCl3) d 11.82 (1H, s), 11.61 (1H,
s),11.52 (1H, s), 11.36 (1H, s), 11.34 (1H, s), 8.53 (1H, d,
J¼7.4 Hz), 8.42 (1H, dd, J¼7.4, 1.3 Hz), 8.32 (1H, d,
J¼7.4 Hz), 8.25 (1H, d, J¼7.4 Hz), 8.17 (1H, d, J¼7.4 Hz),
8.08 (2H, m), 8.03 (1H, d, J¼7.4 Hz, 7.99 (1H, d,
J¼7.4 Hz), 7.82 (1H, d, J¼8.0 Hz), 7.66 (1H, d,
J¼8.0 Hz), 7.49 (1H, s), 7.43 (3H, m), 7.34 (1H,
J¼8.0 Hz), 7.27 (2H, m), 7.17 (1H, m), 7.13 (1H, s), 6.85
(1H, s), 6.76 (1H, s), 6.55 (1H, s), 6.48 (1H, s), 4.39 (1H, m),
4.19 (2H, m), 4.09 (1H, m), 3.98 (6H, m), 3.76 (2H, m), 3.15
(3H, s), 2.44 (5H, m), 2.25 (1H, m),1.30 (24H, m), 1.18
(12H, m). 13C NMR (CDCl3) d 163.76, 163.14, 163.07,
162.96, 162.92, 162.59161.97, 161.27, 161.14, 160.79,
160.15, 160.03, 152.98, 150.46, 149.42, 148.76, 145.244,
144.85, 138.78, 138.36, 138.02, 137.62, 134.14, 133.82,
7.1.4. Synthesis of oligomers 2a, 4a, 6a, and 8a. General
method for coupling an amine and an acid. A solution of
the acid 1e, 2c, or 4c (typically 1 mmol) in excess SOCl2
was heated to reflux for 1 h. Most of the SOCl2 was distilled
off, and the remaining was azeotroped using anhydrous
toluene (5 mL). The acid chloride was dissolved in

H. Jiang et al. / Tetrahedron 59 (2003) 8365–8374
8373
133.72, 133.56, 132.73, 127.95, 127.34, 127.00, 126.88,
126.46, 125.83, 125.77, 123.95, 123.62, 122.65, 122.32,
121.89, 121.71, 121.47, 117.10, 116.90, 116.67, 116.56,
116.34, 115.96, 115.92, 115.64, 100.11, 99.93, 99.75, 98.07,
97.75, 97.72, 75.52, 75.43, 75.38, 75.24, 75.13, 74.74,
52.09, 28.28, 28.19, 28.12, 28.01, 19.48, 19.41, 19.31,
19.22, 19.16. IR (KBr) n, (cm21) 2960, 1684, 1540, 1419,
1357, 1264, 1115, 1051, 878, 760. TOF-MS m/z: 1515.49
[M]þ, 1537.45 [MþNa]þ, 1553.45 [MþK]þ.
structures, the data were collected on a CAD4 Enraf–
Nonius diffractometer with graphite monochromatized
Cu Ka radiation. The cell parameters were determined by
least-squares from the setting angles for 25 reflections. An
empirical absorption correction was applied. The data were
also corrected for Lorentz and polarization effect. The
crystals of 2a are mechanically fragile as well as unstable in
air. During the X-ray exposures, they were sealed with part
of the mother liquor in a Lindemann-glass capillary. The
single crystal was mounted on a Bruker–Nonius k-CCD
diffractometer with graphite monochromatized Mo Ka
Octamer 8a, from acid 4c (0.22 g) and amine 4b (0.2 g).
Yield 0.22 g.(79% based on amine). Yellow solid. Mp:
˚
radiation (0.71073 A). The data collection was based on
1
.2508C. H NMR (CDCl3) d 11.51 (1H, s), 11.38 (1H, s),
f-scans completed by v-scans. The final unit cell was
determined on the basis of all the collected frames. The data
reduction was performed using the COLLECT software
(Nonius, 1998). The positions of non-H atoms were
determined by the program SHELXS 87 and the position
of the H atoms were deduced from coordinates of the non-H
atoms and confirmed by Fourier Synthesis. H atoms were
included for structure factor calculations but not refined.
11.17 (1H, s), 11.09 (1H, s), 11.01 (1H, s), 10.95 (1H, s),
10.93 (1H, s), 8.32 (1H, dd, J¼1.3, 6.7 Hz), 8.21 (1H, dd,
J¼1.3, 6.7 Hz), 8.18 (1H, br), 8.16 (1H, s), 8.11 (2H, td,
J¼6.7, 1.3 Hz), 8.03 (1H, dd, J¼1.3, 6.7 Hz), 7.89 (3H, m),
7.74 (2H, td, J¼7.4, 1.3 Hz), 7.65 (1H, m), 7.54 (1H, m),
7.43 (1H, t, J¼8.0 Hz), 7.39 (1H, t, J¼8.0 Hz), 7.29 (6H,
m), 7.15 (1H, m), 7.06 (1H, s), 7.02 (1H, s), 6.99 (1H, t,
J¼8.0 Hz), 6.67 (1H, s), 6.62 (1H, s), 6.55 (1H, s), 6.51 (1H,
s), 6.37 (1H, s), 6.13 (1H, s), 3.90 (12H, m), 3.67 (4H, m),
3.00 (3H, s), 2.52 (2H, m), 2.35 (5H, m), 2.19 (1H, m), 1.36
(12H, m), 1.20 (36H, m). 13C NMR (CDCl3) d 163.71,
162.80, 162.74, 162.71, 162.62, 162.59, 162.40, 162.31,
161.86, 161.00, 160.77, 160.52, 160.03, 159.71, 159.26,
159.24, 152.99, 149.89, 149.14, 149.08, 148.79, 148.65,
148.09, 144.94, 144.63, 138.64, 138.60, 138.06, 137.96,
137.70, 137.55, 137.51, 137.32, 134.08, 133.55, 133.18,
132.78, 132.64, 127.83, 127.50, 126.87, 126.75, 126.25,
125.74, 125.72, 125.62, 125.49, 123.71, 123.48, 122.53,
122.32, 122.24, 121.54, 121.36, 121.24, 117.23, 116.89,
116.75, 116.64, 116.61, 116.29, 116.17, 116.02, 115.98,
115.92, 115.85, 115.78, 115.46, 99.92, 99.77, 99.49, 99.11,
98.62, 97.82, 97.59, 97.40, 75.46, 75.31, 75.28, 75.22,
75.15, 74.97, 74.65, 51.92, 28.19, 28.16, 28.13, 28.11,
28.07, 28.05, 28.01, 27.91, 19.58, 19.55, 19.51, 19.47,
19.43, 19.36, 19.34, 19.29, 19.22, 19.20, 19.13. IR (KBr) n,
(cm21) 2960, 1684, 1539, 1469, 1419, 1357, 1331, 1264,
1212, 1114, 1053, 878, 817, 759. TOF-MS m/z: 1999.73
[M]þ, 2021.73 [MþNa]þ, 2037.70 [MþK]þ.
Acknowledgements
This work was supported by the Universities of Bordeaux I
and of Bordeaux II, by the Centre National de la Recherche
Scientifique (predoctoral fellowship to C. D.), and by the
`
Ministere de la Recherche (post-docotral fellowship to H. J.).
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Decamer 10a, from acid 2c (10 mg) and amine 8b (17 mg)
was prepared as the other oligomers, but toluene at 808C
overnight was used instead of CH2Cl2 at ambient tempera-
1
ture. Yield 6 mg (29%). Mp: .2508C. Yellow solid. H
NMR (CDCl3) d 11.33 (1H, s), 11.23 (1H, s), 10.96 (1H, s),
10.90 (1H, s), 10.79 (1H, s), 10.70 (1H, s), 10.66 (1H, s),
10.63 (1H, s), 10.60 (1H, s), 8.28 (1H, d, J¼7.4 Hz), 8.10
(1H, d, J¼7.4 Hz), 8.02 (6H, m), 7.78 (2H, t, J¼7.4 Hz),
7.68 (2H, m), 7.52 (1H, d, J¼7.4 Hz), 7.35 (4H, m), 7.20
(12H, m), 6.96 (3H, m), 6.66 (1H, s), 6.51 (1H, s), 6.37 (2H,
d), 6.31 (1H, s), 6.12 (1H, s), 6.10 (1H, s), 6.05 (1H, s), 4.05
(5H, m), 3.89 (8H, m), 3.75 (4H, m), 3.62 (3H, m), 2.93 (3H,
s), 2.31 (10H, m), 1.17 (60H, m). IR (KBr) n, (cm21) 2961,
1684, 1541, 1458, 1418, 1356, 1262, 1210, 1112, 1052, 877,
816, 758. TOF-MS m/z: 2483.61 [M]þ, 2505.58 [MþNa]þ,
2521.57 [MþK]þ.
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The structures of 1a, 1b, 1c, 1d and 2a were determined by
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´
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