Azacalixarene: Synthesis, conformational analysis, and recognition behavior toward anions

Article abstract of DOI:10.1039/a904607k

The synthesis of an azacalix[4]arene (4) having four primary amino groups on the upper rim has been achieved. The synthesis was accomplished by a one-step cyclization starting from two easily synthesized building blocks. ¹H NMR spectra indicate

Full text of DOI:10.1039/a904607k

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Azacalixarene: synthesis, conformational analysis, and recognition
behavior toward anions
Kenichi Niikura and Eric V. Anslyn*
The Department of Chemistry and Biochemistry, The University of Texas at Austin,
Austin, TX 78712, USA
Received (in Gainesville, FL) 7th June 1999, Accepted 3rd September 1999
The synthesis of an azacalix[4]arene (4) having four primary amino groups on the upper rim has been achieved. The
synthesis was accomplished by a one-step cyclization starting from two easily synthesized building blocks. 1H NMR
spectra indicate that this azacalixarene prefers a cone conformation, but that rapid interconversion among different
conformations occurs at room temperature. It is shown that 4 is a useful receptor for sensing various anionic guests,
such as inositol triphosphate (IP3), in aqueous solution. In a competition binding assay, fluorescent probes bound
within 4 were replaced by anionic guests in buffered aqueous solution, causing a modulation in the fluorescence
intensity. NMR spectra of 4 in the presence of fructose 1,6-diphosphate suggest that this guest is bound inside the
cavity which adopts a cone conformation.
Introduction
Calixarenes (1) and related macrocycles have received a lot of
attention due to their molecular recognition properties.1–4 In
recent years, a few azacalixarenes have been synthesized5–7 as
part of a class of compounds called expanded calixarenes (Fig.
1 (2, 3)). The azacalixarenes have nitrogens in the macrocyclic
ring which could provide additional binding sites for guests.
However, in contrast to calixarenes, the azacalixarenes have
not proved as useful for developing receptors. For example,
Hampton and co-workers reported that azacalixarene 2 showed
no significant binding to alkali metal ions due to strong intra-
molecular hydrogen bonds between the hydroxy groups and the
amines in the core of the macrocycle.6 Azacalixarene 3, created
by Robson and co-workers, binds only metals such as Zn2ϩ and
Co2ϩ ions as evidenced by co-crystal structures.7
We believe that azacalixarenes could have great utility as
receptors for a large variety of guests. Specifically, they have
a cationic and hydrophobic cavity which provides binding
sites for anionic guests, and the amines could be modified to
introduce additional functional groups. Furthermore, the
CH2–NH–CH2 linkages introduce flexibility to the receptor,
a feature that may be desirable for binding guests in an induced-
fit fashion. Our interest in water soluble receptors for anionic
guests8 led us to develop the new azacalixarene receptor 4 (Fig.
1).
In this paper, we describe the synthesis, conformational
analysis, and the recognition properties of 4 toward anionic
guests, such as inositol triphosphate (IP3). This is the first report
of such studies using an azacalixarene. As a sensing strategy, we
have applied a probe competition method.9 Fluorescent active
probes (9 and 10) were allowed to bind to 4 in aqueous solution
in the absence of guests. Upon addition of other anionic guests,
the probes were displaced from the binding cavity, resulting
in absorption and fluorescence changes. We demonstrate the
sensing of inositol triphosphate in the 10 µM range in aqueous
solution.
Results and discussion
A. Design criteria
Receptor 4 provides a larger cavity than a normal calix[4]arene,
allowing the binding of anionic carbohydrates such as inositol
triphosphate. Three ethyl groups were introduced into each
benzene ring to impart a preference for the amine groups to be
Fig. 1 Molecular structures of calix[4]arene and azacalixarenes.
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This journal is © The Royal Society of Chemistry 1999
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Fig. 3 1H NMR spectra (500 MHz) of receptor 4 in CD3OD.
Fig. 2 Synthetic route to azacalixarene 4 a) NaN3, DMF, 25 ЊC; b)
TEA, CH2Cl2, 25 ЊC; c) triphenylphosphine, THF and H2O, 25 ЊC.
C. Conformational analysis
The conformation of 4 was determined by 1H NMR spectra at
various temperatures (Fig. 3). There is a significant amount of
analytical data related to the conformation of calixarenes
obtained using NMR techniques.1–3 Our NMR spectra were
compared to those reported for calixarenes. The NMR spectra
observed for 4, discussed below, support structures that are the
cone conformation, but are interconverting rapidly among
isomers on the NMR time scale at 25 ЊC (Fig. 4).
oriented toward the interior of the cavity.10,11 The steric gear-
ing imparted by the ethyl groups was predicted to lead to a
cup conformation of the receptor. We predicted that this pre-
organization would give the receptor a high affinity for the
target molecules. The four secondary amino groups on the
lower rim were included to assist binding of anionic guests in
the bottom of a hydrophobic cavity.
Normal calixarenes carrying amine groups on the top rim
(para-position) exist as zwitterions because the phenols of
calixarenes are stronger acids than monomeric phenols.12 These
intramolecular ion pairs may inhibit the binding of anionic
guests. In contrast, our receptor does not have hydroxy groups
on the rim, thus avoiding zwitterion formation.
To determine the conformation of 4, 1H NMR measurements
were carried out at 50 and 25 ЊC in DMSO-d6 (not shown)
and 25, 0, Ϫ30, and Ϫ70 ЊC in CD3OD (Fig. 3). Proton letter
assignments are shown in Fig. 4. The resonance arising from
the methylene protons a (CH2–NH–CH2 at 4.8 ppm in meth-
anol or 4.5 ppm in DMSO) was found to be a sharp singlet at
temperatures near 50 ЊC and a broad singlet at around 0 ЊC.
This resonance, however, separated into a pair of broad singlets
at temperatures below Ϫ30 ЊC. We found that one of the c pro-
tons (cЉ) and d coincidently overlapped at 25 ЊC, and separated
from each other below Ϫ30 ЊC. Upon cooling the cЉ proton was
shifted downfield.
Two possible scenarios explain the peak resolution of the
a protons found at temperatures below Ϫ30 ЊC. First, two
different conformations of 4 could exist coincidentally in a one-
to-one ratio, where each separated peak for resonances a
corresponds to one of the conformations. The second possibil-
ity is that a stable cone or 1,3-alternate conformation exists at
low temperature and gives rise to separate chemical shifts for
resonances a due to the diastereotopic nature of these centers
(Fig. 4). Neither the 1,2-alternate nor the partial cone con-
formations are supported by the spectra shown in Fig. 3
because these conformations would give significantly more
complex spectra, consisting of many more resonances. Also, the
B. Synthesis
1,3,5-Tris(bromomethyl)-2,4,6-triethylbenzene (5) was syn-
thesized according to a reported procedure.10 The reaction of 5
with 0.8 equivalents of sodium azide in DMF for 24 h at 25 ЊC
gave a mixture of mono-, bis-, and tri-azido substituted com-
pounds (Fig. 2). The mixture was separated using silica gel
chromatography to give a 20% yield of mono-azido compound
6. The tri-azido analog was reduced with an excess of triphenyl-
phosphine to the corresponding tris-amine compound 7 at
25 ЊC over 12 h. The reaction of 7 with half of an equivalent of
6 in CH2Cl2 for 2 days gave compound 8. The purification was
performed by silica gel chromatography to give a white powder
(8) in a yield of 40%. Reduction of 8 to 4 is quantitative in a
mixed solvent of THF and water. Compound 4 was dissolved in
CH2Cl2 and extracted into a 1 M HCl aqueous solution. The
acidic solution was lyophilized to give pure compound 4 as the
octahydrochloride salt.
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Fig. 4 Cone and 1,3-alternate conformation of receptor 4.
Using these correlations and chemical shifts, it is clear that
two conformations do not exist. Two a peaks (aЈ and aЉ) corre-
late with each other, and two c peaks (cЈ and cЉ) also correlate
with each other. These correlations suggest that receptor 4 has
one conformation at Ϫ70 ЊC rather than existing as a mixture
of two different conformations.
Judging from the NOESY spectrum, we conclude that the
conformation of receptor 4 at Ϫ70 ЊC is in the cone conform-
ation. There are three pieces of the data that support this con-
clusion. First, proton cЉ (one of the diastereotopic c protons,
see lettering on Fig. 4) correlates stronger with aЉ but only
weakly or not at all with proton aЈ. In a cone conformation,
protons aЉ are always located above protons aЈ along a hori-
zontal axis through receptor 4, whereas in a 1,3-alternate con-
formation protons aЉ and aЈ alternate up and down relative
to a horizontal axis through the receptor. Therefore protons cЉ
correlate with aЉ in a cone conformation. In contrast, in a
1,3-alternate conformation, protons cЉ should correlate with aЈ
which does not occur here. None of these correlations involves
protons which undergo chemical exchange, and thus the corre-
lations reflect proximity effects.
Further, there are no NOE cross peaks between cЉ and d
protons. The space filling model of receptor 4 indicates that in a
cone conformation, cЉ and d are located far away from each
other as evidenced by the absence of cross peaks in the NOE. In
contrast, in a 1,3-alternate conformation, cЉ is close in space to
d on adjacent benzene rings (Fig. 4). These cross peaks would
be observed in a 1,3-alternate conformation.
As final evidence, the cЉ protons are largely shifted downfield
(ϩ0.25 ppm) from 25 to Ϫ70 ЊC. Since protons cЉ are located
between adjacent benzene rings in a cone conformation, their
chemical shift should be affected by a strong diamagnetic
anisotropy effect, leading to a downfield shift. If the conform-
ation were 1,3-alternate, the cЉ protons would not be affected
because the adjacent benzenes alternate up and down.
Fig. 5 NOESY spectrum of receptor 4 at Ϫ70 ЊC in CD3OD.
orientations of the CH2NH3ϩ groups must all be the same (not
mixtures of all-in, all-out, in and out) due to the simplicity
of the spectra at this temperature. Further, in other highly
charged systems we find alternation of the six groups around
the benzene as presented in our depiction of 4.9
In order to distinguish if two conformations exist, or if a
single conformation exists that is either a cone or 1,3-alternate,
a NOESY spectrum of receptor 4 was recorded at Ϫ70 ЊC (Fig.
5). Before examining the evidence for or against two conform-
ations, we explain the reasons behind assigning chemical shifts.
The resonance for d correlates with a and e since they are close
in space. One of the c protons (labeled as cЈ) correlated stronger
with b than the other c proton (labeled as cЉ). Thus, the proton
located adjacent to b should be cЈ. One of the a protons (labeled
as aЈ) correlated stronger with d than the other a (labeled as aЉ).
This supports aЈ being adjacent to d.
The azacalixarene 4 has a longer spacer, CH2–NH–CH2,
between benzene rings than the one methylene found in calix-
arenes. Due to these longer spacers, azacalixarene 4 should be
more flexible than calixarenes. Furthermore, in calixarenes,
intramolecular hydrogen bonding among the OH groups on the
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benzene rings contributes to the preference of the cone con-
formation in organic solvents.14 In water, as is our case, there
is no intramolecular hydrogen bonding to stabilize the cone
conformation. The increased flexibility and lack of hydrogen
bonding could bring the different conformational isomers
closer in energy. Nevertheless, 4 is frozen in the cone conform-
ation at low temperature. We attribute this to the ethyl groups
attached to the benzene rings, which sterically obligate the
secondary amino groups at the lower rim to be oriented in
the same direction.
D. Recognition behavior
a) Binding behavior toward indicators. Understanding the
binding characteristics of azacalixarene 4 with anionic guests is
our next point of interest. We have previously explored a chemo-
sensing technique using a competition assay with fluorescent
indicators for the detection of specific guests.9 The idea is that
an indicator complexed with a receptor may be replaced by
added guest in solution. Replacement of the indicator leads to a
modulation of the fluorescence or absorbance intensity. For
this purpose we used 5-carboxyfluorescein (9) and 1-hydroxy-
pyrene-3,6,8-trisulfonate (HPTS, 10) as indicators.
Fig. 6 (a) UV–visible absorption spectra of 9 upon addition of 4. (b)
10 upon addition of 4. All in 10 mM HEPES buffer (pH = 7.2),
[9] = [10] = 7.5 µM. [4] = 0–50 µM.
Both of these probes are pH indicators which are very sensi-
tive to their surrounding microenvironment.15,16 We tested
whether these indicators bind to receptor 4. Fig. 6 shows the
absorbance change upon addition of receptor 4 to the indi-
vidual solutions of 9 and 10 (HEPES buffer, 10 mM, pH 7.2).
The intensity of λmax (490 nm) of 9 decreased with increasing
concentration of receptor 4, whereas that for 10 increased (Fig.
6). In both cases, UV–Vis spectra revealed an isosbestic point,
which supports a one-to-one complex between the probes and
the receptor. The association constants for the complexes were
determined using the Benesi–Hildebrand method,17 giving
constants of 9.3 × 103 and 50 × 103 MϪ1 for 4 with 9 and 10
respectively.
We also conducted a 1H NMR study to confirm the binding
stoichiometry in methanol. The chemical shift of proton b was
plotted as a function of mole ratio [4]/[10]. The change in
chemical shift decreased linearly with increasing [10]. At a one-
to-one host–guest ratio, the line cleanly changed to a slope
of zero, indicating that 10 binds to receptor 4 in a one-to-one
complex with an association constant larger than can be deter-
mined using 1H NMR.
b) Binding behavior toward phosphorylated carbohydrates.
The fluorescence intensity of 10 decreased with increasing [4]
when 10 was excited at 390 nm (Fig. 7(a)). This decrease in
fluorescence intensity can be explained by a decrease in the
protonation state of the hydroxy group on HPTS after binding
to the receptor 4.16
As anticipated, based upon the difference in the spectroscopy
of 10 when it is bound to 4 versus when it is free in solution,
addition of inositol triphosphate (IP3) to a solution of receptor
4 and 10 resulted in an increase of fluorescence (Fig. 7(b)) due
to the release of 10 into the solution. Fig. 8 shows the fluor-
escent change of 10 as a function of guest concentration of
four different anionic guests. As anionic guests, we chose IP3
(11), fructose 1,6-diphosphate (12), gluconic acid (13), and
Fig. 7 (a) Fluorescence spectra of 10 upon addition of 4 (0, 1.3, 4, 9,
23, 31, 50 µM). (b) 10 upon addition of IP3 (0, 3.6, 9.7, 15.7, 22, 40 µM)
in the presence of 4. All in 10 mM HEPES buffer (pH = 7.2). [4] = 30
µM, [10] = 7.5 µM, Excited at 390 nm.
adamantane-1,3-dicarboxylic acid (14). From a space filling
model, we predicted that these guests could be bound inside the
cavity of the cone conformation. The fluorescence intensities
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Table 1 Binding constants (Ka) of anionic guests with receptor 4 in
HEPES buffer (10 mM, pH 7.2)
Guest
Ka/103 MϪ1
9
10
11
12
13
14
9.3
50
240
12
3.0
<1.0
Fig. 9 NMR chemical shifts of receptor 4 upon addition of fructose
1,6-diphosphate (12) function of concentration ratio, [4]/[10]. [4] = 8.4
µM. See Fig. 5 for proton positions, (a), (b), (c), and (d).
hindrance between the guest and ethyl groups of 4 (see 1,3-
alternate conformation as an example).
Upon addition of 12, the overlapped resonance peak for the
cЉ and d protons was shifted upfield, and also the resonance for
the cЈ protons was slightly shifted. This suggests that the cЉ and
d protons interact with 12 more strongly than the cЈ protons. In
a cone conformation these three protons face the cavity and the
cЉ and d protons are located deeper in the cavity than the cЈ
protons (Fig. 4). This can be explained by an interaction of 12
with receptor at the bottom of the cavity of a cone conform-
ation while the phosphates of 12 are bound to the amines of the
lower rim.
Fig. 8 Fluorescence spectral changes at 450 nm of 10 upon addition
of anionic guest in HEPES buffer, 10 mM, pH 7.2. [4] = 30 µM, [10] =
7.5 µM, Excited at 390 nm: ᭿ = 11, ᭺ = 12, ᭡ = 13, and ᮀ = 14.
Conclusion
A new azacalixarene has been designed and synthesized. Aza-
calixarene 4 is a flexible molecule at 25 ЊC. Receptor 4 bound
anionic indicators in a one-to-one fashion and the indicators
can be replaced by anionic guests. This replacement was
detected as changes in both the UV–vis and fluorescence spec-
tra of the anionic indicators. This demonstrates the usefulness
of azacalixarenes as receptors for anionic guests. We further
demonstrate that the probe competition method can be widely
applied to create sensing systems for receptors that do not con-
tain covalent chromophores. Modification of the N-substitu-
ents is currently being investigated to generate new receptors for
the inclusion of organic and inorganic molecules.
became saturated with increasing guest concentrations. Accord-
ing to reported procedures treating competition assays,9,17 these
curves were transferred to lines. From the slopes, binding con-
stants were calculated. Table 1 shows the binding constants of
receptor 4 for these anionic guests in HEPES buffer, 10 mM,
pH 7.2. Although receptors having multiple amino groups tend
to lose the specificity for anionic guests9b,18 and often precipi-
tate, receptor 4 can strongly associate with anionic guests in
water.
Experimental
1) General considerations
All solvents and reagents were purchased from Aldrich Chem-
ical Co., and were used as received. NMR spectra were recorded
on 300 or 500 MHz Varian Unity instruments. Chemical shifts
were referenced to solvent peaks. UV–vis spectra were recorded
on a Beckman DU70 spectrometer and fluorescence spectra
were recorded on an SPF-5000 C spectrofluorometer. Melting
points were measured on a Thomas Hoover capillary melting-
point apparatus and are uncorrected. Preparative flash chrom-
atography was performed on Whatman 60 Å 230–400 mesh
silica gel. Reactions were run under N2 atmospheres.
1
We investigated the H NMR spectra of receptor 4 upon
addition of fructose 1,6-diphosphate (12) in methanol. Chem-
ical shifts of protons a, b, c, and d were followed with increasing
concentration of 12 and mole ratio plots created (Fig. 9). The
resonances for the methylene protons (a) (same lettering system
as given in Fig. 4) were largely shifted upfield. However, the
resonance for b was not shifted significantly. Upfield shifts of
the methylene protons on the bottom rim suggest that 12 sits on
the bottom rim and binds to the cyclic secondary amines. The
lack of a chemical shift in the b protons implies that 12 does
not contact the primary amines at the upper rim. Macrocyclic
polyamines have been reported to provide high affinities for
anions such as phosphate ions.19,20 Only a conformation of
receptor 4 can provide the cyclic secondary amines for bind-
ing sites because flipping of benzene rings could cause steric
2) Conformational analysis
Azacalixarene 4 as its chloride salt (10 mg) was dissolved in
1
methanol-d4 and DMSO-d6. H NMR (500 MHz) measure-
ments were carried out at 50 and 25 ЊC for DMSO-d6 solutions
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and at 25, 0, Ϫ30, Ϫ70 ЊC for methanol-d4 solutions. NOESY
spectra were recorded at Ϫ70 ЊC in methanol-d4. Resonance
signals from solvents were used as a standard reference.
(160 mg, 0.16 mmol) and triphenylphosphine (500 mg, 1.9
mmol) were dissolved in THF (100 ml) and H2O (10 ml). The
mixture was stirred at 25 ЊC for one day. The solvent was evap-
orated and the residue was taken up in CH2Cl2 (100 ml) to
which was added 0.1 M HCl (100 ml). The aqueous layer was
washed CH2Cl2 three times and lyophilized twice to give 210 mg
of pure white compound. Yield: quantitative; mp: decomposed
3) Binding studies
A solution of receptor 4 (30 µM) was titrated into a 1.5 ml
solution of 5-carboxyfluorescein (9) or HPTS (10) (2 µM) in
HEPES buffer (pH 7.2, 10 mM) at 25 ЊC. Absorbances at 490
nm for 9 and 400 nm for 10 were measured. Standard curves of
absorbance as a function of concentration of the receptor were
transferred to Benesi–Hildebrand plots.17 From their slopes,
we obtained the binding constants of probes for receptor 4.
As a competition method, concentrated aqueous solutions of
anionic guests 11, 12, 13, and 14 were respectively added to a
solution of receptor 4 (10 µM) and HPTS (2 µM) in HEPES
buffer (10 mM, pH 7.2). The solutions were excited at 390 nm
and emission spectra at 513 nm were collected upon addition of
anionic guests. Binding constants were obtained according to
previously published procedures.9,13
1
over 250 ЊC; H NMR (500 MHz, CD3OD) δ 4.7019 (16H, bs,
CH2NHCH2), 4.297 (4H, bs, CH2NH3), 3.0742 and 2.9319
(24H, bs, CH2CH3), 1.361 and 1.253 (36H, bs, CH2CH3); 13C
NMR (125 MHz, CD3OD) δ 8.144 (CH2NH3), 26.167 and
27.42 (CH2CH3), 18.11 and 17.3 (CH2CH3), 127.451, 129.415
and 149.386 (Ar); HRMS(FAB): 934.062 (C60H101N8, calcd.
934.1059).
Acknowledgements
We gratefully acknowledge support for this work from the
Texas Advanced Technology Program and the Welch Found-
ation. K. N. thanks the Japanese Society for the Promotion of
Science for a fellowship.
An NMR titration was carried out for fructose 1,6-diphos-
phate. Receptor 4 (5 mg) was dissolved in methanol-d4 (800 µl)
in an NMR tube. Fructose 1,6-diphosphate (35 mg) was dis-
solved in 1 ml D2O. Aliquots of the guest aqueous solution were
added to the receptor solution in an NMR tube.
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Synthesis
[3,5-Bis(bromomethyl)-2,4,6-triethylphenyl]methyl azide (6).
1,3,5-Tris(bromomethyl)-2,4,6-triethylbenzene (5) (19.1 g, 44
mmol) and sodium azide (2.2 g, 35 mmol) were dissolved in
DMF (100 ml). This mixture was stirred at room temperature
for one day. The solvent was removed by a rotary evaporator.
The residue was taken up in ether (200 ml) and washed with
brine three times. The organic layer was dried with Na2SO4,
filtered, and evaporated. The crude solid was purified by flash
column chromatography with gradient elution of 1% to 5%
methanol in DCM. The compound at Rf = 0.8 was collected as
1
a white powder. Yield 18%; mp 103 ЊC; H NMR (300 MHz,
CDCl3) δ 4.47 (2H, s, CH2N3), 4.58 (4H, s, CH2Br), 2.88 (6H, m,
CH2CH3), 1.30 (9H, m, CH2CH3); 13C NMR (75 MHz, CDCl3)
δ 15.8, 15.9, 23.2, 23.3, 48.5, 131.1, 133.0, 145.1, 145.5;
HRMS(FAB) 401.009 (C15H21N3Br2, calcd. 401.010).
[23-(Aminomethyl)-3,11,19,27-tetraaza-15,31-bis(azido-
methyl)-6,8,14,16,22,24,30,32,33,34,35,36-dodecaethylpenta-
cyclo[27.3.1.15,9.113,17.121,25]hexatriaconta-1(33),5,7,9(34),13,15,
17(35),21,23,25(36),29,31-dodecaen-7-yl]methylamine (8). 1,3,5-
Triethyl-2,4,6-tris(aminomethyl)benzene (7, 1.5 g, 6.0 mmol)
and triethylamine (5 ml) were dissolved in CH2Cl2 (125 ml).
Compound 6 (1.5 g, 15 mmol) dissolved in CH2Cl2 (50 ml) was
added dropwise for one hour. This ratio of reactants gave the
best yields. The mixture was stirred for 2 days at 25 ЊC. During
stirring, a white precipitate formed. The resulting solution was
washed with brine three times, and the organic layer was dried
with Na2SO4, filtered, and evaporated to give a white solid. The
crude material was purified by flash column chromatography
with 1% methanol in CH2Cl2 as eluent. The compound at
Rf = 0.8 was collected. mp: decomposed over 200 ЊC; yield
40%; 1H NMR (300 MHz, CDCl3) δ 4.39 (4H, s, CH2N3), 3.80
(20H, s, CH2NHCH2 and CH2NH3), 2.84 (24H, m, CH2CH3),
1.35 and 1.24 (36H, m, CH2CH3); 13C NMR (75 MHz, CDCl3)
δ 48.7, 48.6 (CH2–NH–CH2), 48.1 (CH2N3), 39.5 (CH2NH2),
22.7 and 22.5 (CH2CH3), 17.1 and 16.5 (CH2CH3), 128.7, 133.7,
141.2 and 143.4 (Ar); HRMS(FAB): 981.763 (C60H96N12, calcd.
981.764).
[3,11,19,27-Tetraaza-6,8,14,16,22,24,30,32,33,34,35,36-
dodecaethyl-15,23,31-tris(aminomethyl)pentacyclo[27.3.1.15,9.
113,17.121,25]hexatriaconta-1(32),5(34),6,8,13(35),14,16,21(36),
22,24,29(33),30-dodecaen-7-yl]methylamine (4). Compound 8
2774
J. Chem. Soc., Perkin Trans. 2, 1999, 2769–2775

View Article Online
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