Synthesis of nitrogen- and oxygen-containing macrocycles by palladium-catalyzed amination of 3,24-bis(6-chloropyridin-2-yloxy)cholane

Article abstract of DOI:10.1134/S1070428009010114

3,24-Bis(6-chloropyrdin-2-yloxy)cholane prepared from cholane-3,24-diol by the Mitsunobu reaction was successfully used to synthesize various polyaza macrocycles via palladium-catalyzed amination with linear polyamines. The contribution of side formation of cyclic oligomers was found to depend on the polyamine nature.

Full text of DOI:10.1134/S1070428009010114

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 1, pp. 78–86. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.D. Averin, E.R. Ranyuk, N.V. Lukashev, A.K. Buryak, I.P. Beletskaya, 2009, published in Zhurnal Organicheskoi Khimii, 2009,
Vol. 45, No. 1, pp. 85–93.
Synthesis of Nitrogen- and Oxygen-Containing Macrocycles
by Palladium-Catalyzed Amination of 3,24-Bis(6-chloropyridin-
2-yloxy)cholane
A. D. Averina, E. R. Ranyuka, N. V. Lukasheva, A. K. Buryakb, and I. P. Beletskayaa, b
a Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
e-mail: averin@org.chem.msu.ru
b Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences,
Leninskii pr. 31, Moscow, 119991 Russia
e-mail: beletska@org.chem.msu.ru
Received April 15, 2008
Abstract—3,24-Bis(6-chloropyrdin-2-yloxy)cholane prepared from cholane-3,24-diol by the Mitsunobu
reaction was successfully used to synthesize various polyaza macrocycles via palladium-catalyzed amination
with linear polyamines. The contribution of side formation of cyclic oligomers was found to depend on the
polyamine nature.
DOI: 10.1134/S1070428009010114
Macrocyclic compounds containing 2–4 cholic acid
fragments that are linked through various spacers are
referred to as cholaphanes, and they attract consider-
able interest from the viewpoint of design of molecular
sensors. Steroid fragments can be linked to each other
through amide [1–3], ether [4–8], and polyether (ethyl-
ene glycol) bridges [9]. Another group of macrocycles
based on steroid scaffold includes those resembling
crown ethers; such structures are obtained by attach-
ment of a polyoxaalkyl chain at two positions of the
steroid molecule [10–13]. We recently developed an-
other synthetic approach to macrocycles containing
steroid fragments. It is based on palladium-catalyzed
amination of haloaryl derivatives of cholanediol with
linear polyamines [14, 15]. In the present article we
describe a catalytic synthesis of cholanediol-based
macrocycles with pyridine fragments as aromatic spac-
ers. Our choice was dictated by the presence of a ni-
trogen atom in the pyridine ring, which was expected
to enhance complexing power of the resulting macro-
cycles and probably their biological activity.
In this case we observed selective and complete substi-
tution at the C24 atom, in contrast to analogous reaction
with 3-bromophenol [14]. Treatment of diol II with
2.5 equiv of 6-chloropyridin-2-ol under similar condi-
tions gave 85% of 3,24-bis(6-chloropyridin-2-yloxy)-
cholane (IV).
Compound IV was subjected to palladium-cata-
lyzed amination [17, 18] with various polyamines Va–
Vi (Scheme 2). The reactions were carried out in boil-
ing dioxane at a reactant concentration of 0.02 M using
Pd(dba)2/BINAP (8–9 mol %) as catalyst and sodium
tert-butoxide as base. The reactions were complete in
1
15 h, and the reaction mixtures were analyzed by H
and 13C NMR spectroscopy before chromatographic
separation. Macrocyclic compounds VI were isolated
by column chromatography on silica gel, and their
yields strongly depended on the polyamine nature,
primarily on the length of the aminoalkyl chain.
In the reaction with short-chain propane-1,3-di-
amine (Va) we obtained only cyclic dimer VIIa in
38% yield (see table, run no. 1). An additional amount
of compound VIIa (21%) was also isolated as a sepa-
rate fraction which also contained BINAP dioxide and
dioxane at a molar ratio of 4:1:2. The reaction with
triamine Vb gave 25% of cyclic dimer VIIb and 46%
of an inseparable mixture of cyclic dimer VIIb, trimer
VIIIb, and tetramer IXb (run no. 2). The target macro-
Cholane-3,24-diol (II) was synthesized in 90%
yield by reduction of lithocholic acid (I, 3α-hydroxy-
5β-cholan-24-oic acid) with diborane in anhydrous
tetrahydrofuran. The Mitsunobu reaction [16] of II
with 1 equiv of 6-chloropyridin-2-ol gave 24-(6-chloro-
pyridin-2-yloxy)cholane (III) in 84% yield (Scheme 1).
78

SYNTHESIS OF NITROGEN- AND OXYGEN-CONTAINING MACROCYCLES
79
Scheme 1.
Me
Me
Me
Me
O
OH
OH
NaBH4–BF3, THF
Me
H
H
Me
H
H
H
H
H
H
HO
HO
I
II, 90%
Me
Me
1 equiv
O
N
Me
H
Cl
H
H
Cl
N
OH
HO
Ph3P, DEAD, THF
H
III, 84%
Me
Me
2.5 equiv
O
N
Me
H
Cl
H
H
Cl
N
O
H
IV, 85%
cycle VIb was detected only in trace amount by
MALDI-TOF mass spectrometry (m/z 616.3 [M + H]+).
Triamine Vc having a longer aminoalkyl chain reacted
with compound IV to afford 9% of macrocycle VIc;
however, the latter was isolated in a mixture with cy-
clic dimer VIIc (12%). In addition, a fraction contain-
ing dimer VIIc, trimer VIIIc, and tetramer IXc (over-
all yield 33%, run no. 3) was isolated. Analogous result
was obtained in the reaction with N,N′-bis(3-aminopro-
pyl)ethane-1,2-diamine (Vd): the yield of VId was 7%
(in a mixture with dimer VIId, run no. 4). Appreciably
higher yield of the desired macrocyclic compound was
obtained with N,N′-bis(3-aminopropyl)propane-1,3-di-
amine (Ve); compound VIe was isolated in 29% yield,
and the product was separated from dimer VIIe (66%,
run no. 5). The reaction with diamine Vf containing
an adamantane fragment gave no corresponding macro-
cycle VIf, presumably because of insufficient length of
the spacer; the yield of cyclic dimer VIIf was 15%,
and the overall yield of higher cyclic oligomers was
Reaction of 3,24-bis(6-chloropyrdin-2-yloxy)cholane (IV) with polyamines Va–Vi
Run no. Amine Macrocycle, yield, % Cyclic dimers and oligomers, yield, %
1
2
3
4
5
6
7
8
9
Va
Vb
Vc
Vd
Ve
Vf
Vg
Vh
Vi
VIa, 0
VIb, traces
VIc, 9
VId, 7
VIe, 29
–
VIIa, 38; VIIa/BINAP dioxide/dioxane (4:1:2), 21
VIIb, 25; VIIb/VIIIb/IXb, 46
VIIc, 12; VIIc/VIIIc/IXc, 33
VIId, 19
VIIe, 66
VIIf, 15; higher oligomers, 22
VIIg/VIIIg, 14; higher oligomers, 60
VIIh, 12; higher oligomers, 23
VIIi, 10; higher oligomers, 33
VIg, 6
VIh, 22
VIi, 21
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

AVERIN et al.
80
Scheme 2.
Me
Me
Me
Me
O
O
Me
H
H
Me
H
H
H2NCH2CH2XCH2CH2NH2 (Va–Vi)
Pd(dba)2/BINAP (8–9 mol %)
t-BuONa, dioxane, 100°C, 15 h
N
N
H
H
H
H
Cl
HN
O
O
N
N
X
Cl
N
H
IV
VIb–VIe, VIg–VIi
Me
Me
O
Me
H
H
X
N
+
H
H
O
N
H
N
N
H
n
VII–IX
H
N
H2N
NH2
H2N
NH2
H2N
N
NH2
H
Va
Vb
Vc
H
N
NH2
H2N
N
H
H2N
N
N
NH2
H2N
O
NH2
H
H
Vd
Ve
Vf
O
NH2
NH2
H2N
O
H2N
O
Vg
Vh
O
H2N
O
O
NH2
Vi
VII, n = 2; VIII, n = 3; IX, n = 4; dba is dibenzylideneacetone.
22% (run no. 6). The reactions of IV with di- and tri-
oxaalkane-α,ω-diamines Vg–Vi gave similar results.
The shortest diamine Vg gave rise to only 6% of
macrocycle VIg (run no. 7), while the yields of VIh
and VIi from diamines Vh and Vi having a longer
chain were 22 and 21%, respectively (run nos. 8, 9).
from those obtained by us previously with 3,24-bis(3-
bromophenoxy)cholane [14]. Poor yields of the target
macrocyclic compounds VI and formation of large
amounts of oligomeric products may be rationalized in
terms of reduced reactivity of chlorine atom in cata-
lytic amination. This may led to low rate of the intra-
molecular amination after replacement of the first
chlorine atom in IV. The open-chain intermediate thus
The results of catalytic amination of 3,24-bis(6-
chloropyridin-2-yloxy)cholane (IV) somewhat differ
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SYNTHESIS OF NITROGEN- AND OXYGEN-CONTAINING MACROCYCLES
formed is capable of reacting with the second molecule EXPERIMENTAL
81
of IV, giving rise to oligomeric products despite low
reactant concentration. It should also be noted that
cyclic dimers VII may be formed as “head-to-head”
and “head-to-tail” regioisomers. The number of pos-
sible regioisomers for higher oligomers VIII and IX is
even greater.
The H and 13C NMR spectra were recorded from
solutions in CDCl3 on a Bruker Avance-400 spectrom-
eter at 400 and 100.6 MHz, respectively, using the
solvent signals as reference (CHCl3, δ 7.25 ppm;
CDCl3, δC 77.00 ppm). The MALDI-TOF mass spectra
(positive ion registration) were obtained on a Bruker
Daltonics Ultrafex instrument using 1,8,9-trihydroxy-
anthracene as matrix. Preparative column chromatog-
raphy was performed on Merck silica gel (40–60 μm).
Lithocholic acid (I), sodium tetrahydridoborate, boron
trifluoride–ether complex, polyamines Va–Ve and Vg–
Vi, sodium tert-butoxide, and cesium carbonate were
commercial products which were used without addi-
tional purification. Bis(dibenzylideneacetone)palladi-
um(0) [Pd(dba)2] was synthesized according to the
procedure described in [19] without additional recrys-
tallization. 2,2′-(Adamantane-1,3-diyl)di(ethanamine)
(Vf) was prepared as reported in [20]. Dioxane and
tetrahydrofuran were distilled first over alkali and then
over metallic sodium, diethyl ether was distilled over
alkali, and methylene chloride and methanol were
distilled prior to use.
1
The 1H NMR spectra of compounds VI characteris-
tically contained a signal at δ 5.30–5.35 ppm from
proton on C3; in addition, a large difference in the
chemical shifts of diastereotopic protons on C24 was
observed (δ 4.0–4.3 ppm). Oxa diamine derivatives
VIg–VIi displayed a large difference in the chemical
shifts of the two NH protons (Δδ = 0.3–0.5 ppm). In
1
the H NMR spectra of cyclic dimers VII, protons on
C3 resonated in a stronger field (δ 5.0–5.2 ppm); in
some cases the 3-H signal appeared as two nearby
broadened singlets with different intensities due to the
presence of two regioisomers. The spectra of cyclic
dimers showed no difference in the chemical shifts of
diastereotopic protons on C24 and NH protons; the
corresponding signals were broadened singlets. In the
13C NMR spectra of compounds VI, the C14 and C17
signals were located at δC 57–58 and 53–54 ppm, i.e.
the difference in the chemical shifts is 3–4 ppm. Anal-
ogous signals in the spectra of cyclic dimers VII ap-
peared close to each other (δC 55–56 ppm). Some car-
bon atoms in dimers VII gave rise to a set of closely
located singlets with different intensities instead of one
singlet. This pattern was observed for carbon atoms in
the polyazaalkyl chain, C14 and C17 in the steroid frag-
ment, and carbon atoms in positions 3 and 5 of the pyr-
idine rings. Probable reasons are both the presence of
two regioisomers and restricted rotation in the polyaza-
alkyl chains due to intramolecular hydrogen bonding.
An indirect support for the latter factor is provided by
appreciable reduction in the multiplicity of signals in
3α,5β-Cholane-3,24-diol (II). A 500-ml two-
necked flask equipped with a dropping funnel, reflux
condenser, and magnetic stirrer was filled with argon
and charged with 4.92 g (113 mmol) of sodium tetra-
hydridoborate, 5.61 g (15 mmol) of lithocholic acid
(I), and 150 ml of anhydrous tetrahydrofuran, and
18.5 ml (150 mmol) of boron trifluoride–ether com-
plex was added dropwise under stirring. During the
addition, an abundant white curdy material separated.
When the entire amount of BF3·Et2O was added, the
mixture was stirred for 24 h and carefully treated with
100 ml of a saturated aqueous solution of sodium
chloride, 200 ml of water was added until complete
dissolution of boric acid, and the mixture was extract-
ed with methylene chloride (300 ml). The aqueous
phase was washed with methylene chloride (2 ×
100 ml), the washings were combined with the extract
and dried over sodium sulfate, and the solvent was
distilled off under reduced pressure. The residue was
cholanediol II as a colorless powder which was recrys-
tallized from 400 ml of acetone. Yield 4.88 g (90%),
1
going from CDCl3 to DMSO-d6. The H NMR spectra
recorded from solutions in DMSO-d6 also revealed
a considerable downfield shift of the NH signals
(δ 6.5–6.7 ppm). Unfortunately, signals from several
carbon atoms in the steroid skeleton were overlapped
by the CD3 multiplet of the solvent (DMSO-d6). Final-
ly, no appreciable differences in the spectral patterns of
cyclic dimers and higher cyclic oligomers were ob-
served, except for broadening of all signals in the 1H
and 13C NMR spectra. Macrocycles VI give much
more intense signals in the MALDI mass spectra, as
compared to cyclic dimers VII; therefore, this method
cannot be used to estimate their ratio in the reaction
mixtures on a quantitative level.
1
mp 172–173°C. H NMR spectrum (CDCl3), δ, ppm:
0.63 s (3H), 0.91 s (3H), 0.92 d (3H, J = 5.6 Hz),
0.95–1.89 m (27H), 1.93–1.97 m (1H), 3.55–3.65 m
(3H). 13C NMR spectrum (CDCl3), δC, ppm: 12.0,
18.6, 20.8, 23.4, 24.2, 26.4, 27.2, 28.3, 29.4, 30.6,
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009

AVERIN et al.
82
31.8, 34.6, 35.3, 35.6, 35.9, 36.5, 40.2, 40.5, 42.1,
42.7, 56.2, 56.5, 63.6, 71.9.
of polyamine Va–Vi and 144 mg (1.5 mmol) of sodium
tert-butoxide were added, and the mixture was heated
for 15 h under reflux. The mixture was cooled, the
liquid phase was separated by decanting, the solid
phase was washed with a small amount of methylene
chloride, the washings were combined with the organic
solution and evaporated under reduced pressure, and
the residue was subjected to chromatography on silica
gel using the following solvent systems as eluents (in
succession): CH2Cl2, CH2Cl2–MeOH (500:1 to 3:1),
and CH2Cl2–MeOH–aq. NH3 (100:20:1 to 10:4:1).
24-(6-Chloropyridin-2-yloxy)-3α,5β-cholane
(III). A mixture of 3 mmol (1.086 g) of cholane-3,24-
diol (II), 75 ml of anhydrous THF, 3 mmol (389 mg)
of 6-chloropyridin-2-ol, 3 mmol (786 mg) of triphenyl-
phosphine, and 3 mmol (534 mg or 1.38 ml of a 40%
solution in toluene) of diethyl azodicarboxylate was
stirred for 24 h under argon at room temperature. Most
part of the solvent was distilled off under reduced pres-
sure, diethyl ether was added to precipitate triphenyl-
phosphine oxide, and the latter was filtered off. The
transparent filtrate was evaporated under reduced pres-
sure, and the residue was subjected to chromatography
on silica gel using methylene chloride as eluent. Yield
Cyclic dimer VIIa was obtained from 0.56 mmol
(328 mg) of compound IV and 0.56 mmol (42 mg) of
propane-1,3-diamine (Va). Eluent CH2Cl2–MeOH
(25:1 to 5:1). Yield 126 mg (38%), light yellow crys-
1
1
tals, mp 146–148°C. H NMR spectrum (CDCl3), δ,
1.186 g (84%), colorless oily substance. H NMR
3
ppm: 0.65 s (6H), 0.94 d (6H, J = 6.4 Hz), 0.96 s
spectrum (CDCl3), δ, ppm: 0.60 s (3H), 0.87 s (3H),
0.90 d (3H, 3J = 6.5 Hz), 0.95–1.96 m (28H), 2.14 br.s
(1H), 3.52–3.61 m (1H), 4.15–4.24 m (2H), 6.58 d
(1H, 3J = 8.0 Hz), 6.82 d (1H, 3J = 7.6 Hz), 7.45 t (1H,
J = 7.8 Hz). 13C NMR spectrum (CDCl3), δC, ppm:
12.1, 18.6, 20.8, 23.4, 24.2, 25.5, 26.4, 27.2, 28.2, 30.6,
32.0, 34.6, 35.3, 35.5, 35.8, 36.5, 40.2, 40.4, 42.1,
42.7, 56.2, 56.5, 67.2, 71.9, 109.1, 116.0, 140.4, 148.3,
163.8. MALDI-TOF mass spectrum: m/z 473.4 [M]+.
3
(6H), 0.99–2.03 m (60H), 3.35 d.t (8H, J = 7.3,
6.1 Hz), 4.08–4.18 m (4H), 4.49 br.s (4H), 5.15 s (2H),
3
3
5.88 d (2H, J = 7.9 Hz), 5.91 d (2H, J = 8.1 Hz),
5.98 d (4H, 3J = 7.9 Hz), 7.29 t (2H, 3J = 7.6 Hz), 7.30 t
(2H, J = 7.7 Hz). 13C NMR spectrum (CDCl3), δC,
3
ppm: 12.1 (2C), 18.7 (2C), 21.1 (2C), 23.8 (2C), 24.2
(2C), 25.0 (2C), 25.8 (2C), 26.3 (2C), 26.7 (2C), 28.3
(2C), 29.8 (2C), 30.7 (4C), 32.2 (2C), 34.9 (2C), 35.6
(2C), 35.7 (2C), 37.2 (2C), 39.8 (4C), 40.0 (2C), 40.3
(2C), 42.8 (2C), 56.3 (2C), 56.7 (2C), 66.3 (2C), 70.5
(2C), 97.3 (4C), 97.7 (2C), 98.2 (2C), 139.8 (2C),
139.9 (2C), 157.8 (4C), 163.0 (2C), 163.5 (2C).
MALDI-TOF mass spectrum: m/z 1173.2 [M]+. The
subsequent elution with CH2Cl2–MeOH (50:1) gave
a fraction containing 94 mg of a mixture of VIIa with
BINAP dioxide and dioxane at a molar ratio 4:1:2
(weight fraction of VIIa 21%, 69 mg), mp 125–127°C.
3,24-Bis(6-chloropyridin-2-yloxy)-3α,5β-cholane
(IV) was synthesized in a similar way from 3.7 mmol
(1.344 g) of diol II and 9.25 mmol (1.198 g) of
6-chloropyridin-2-ol in the presence of 9.25 mmol
(2.424 g) of triphenylphosphine and 9.25 mmol
(1.646 g or 4.25 ml of a 40% solution in toluene) of
diethyl azodicarboxylate in 100 ml of anhydrous THF.
Yield 1.841 g (85%), colorless oily substance. 1H NMR
spectrum (CDCl3), δ, ppm: 0.65 s (3H), 0.94 d (3H,
3J = 6.4 Hz), 0.97 s (3H), 1.02–2.03 m (28H), 4.20–
Cyclic dimer VIIb was obtained from 0.4 mmol
(234 mg) of compound IV and 0.4 mmol (41 mg) of
triamine Vb. Eluent CH2Cl2–MeOH–aq. NH3 (100:
20:1 to 100:20:2). Yield 62 mg (25%), light yellow
3
4.28 m (2H), 5.31 br.s (1H), 6.60 d.d (1H, J = 8.2,
3
4
4J = 0.6 Hz), 6.62 d.d (1H, J = 8.2, J = 0.6 Hz),
6.82 d.d (1H, 3J = 7.4, 4J = 0.6 Hz), 6.86 d.d (1H, 3J =
1
oily substance. H NMR spectrum, δ, ppm: in CDCl3:
4
3
0.65 (6H), 0.93 d (6H, 3J = 7.2 Hz), 0.94 s (6H), 0.98–
7.4, J = 0.6 Hz), 7.46 t (1H, J = 7.8 Hz), 7.49 t (1H,
3J = 7.8 Hz). 13C NMR spectrum (CDCl3), δC, ppm:
12.1, 18.6, 21.1, 23.8, 24.2, 24.8, 25.4, 26.2, 26.6,
28.2, 30.4, 30.6, 32.0, 34.9, 35.4, 35.7, 37.2, 39.9,
40.2, 42.7, 56.1, 56.6, 67.2, 71.9, 109.1, 109.7, 115.6,
115.9, 140.4 (2C), 148.3 (2C), 163.2, 163.7. MALDI-
TOF mass spectrum: m/z 584.5 [M]+.
2.02 m (56H), 3.23 br.s (8H), 3.73 br.s (8H), 3.92–
3
4.06 m (4H), 5.02 br.s (2H), 5.91 d (2H, J = 7.8 Hz),
3
3
5.93 d (2H, J = 7.9 Hz), 5.98 d (2H, J = 8.4 Hz),
3
6.02 d (2H, J = 8.4 Hz), 7.17–7.28 m (4H); signals
from six NH protons were not assigned unambiguous-
ly; in DMSO-d6: 0.58 s and 0.61 s (6H), 0.86 d (6H,
3J = 5.4 Hz), 0.90 s and 0.91 s (6H), 0.95–1.95 m
Macrocyclic compounds VI and cyclic dimers
VII (general procedure). A mixture of 0.5 mmol of
compound IV, 24 mg (8 mol%) of Pd(dba)2, 28 mg
(9 mol%) of BINAP, and 25 ml of anhydrous 1,4-di-
oxane was stirred for 2–3 min under argon, 0.5 mmol
3
(56H), 3.10 t (8H, J = 5.7 Hz), 3.50 br.s (8H), 4.01–
3
4.18 m (4H), 5.12 s and 5.16 s (2H), 5.86 d (2H, J =
3
3
7.3 Hz), 5.87 d (2H, J = 7.2 Hz), 6.00 d (2H, J =
3
3
8.0 Hz), 6.02 d (2H, J = 7.7 Hz), 6.74 t (4H, J =
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SYNTHESIS OF NITROGEN- AND OXYGEN-CONTAINING MACROCYCLES
83
5.5 Hz), 7.23–7.30 m (4H); signals from two NH
protons were not assigned unambiguously. C NMR
34.8, 35.1, 37.2, 39.7, 39.9, 40.6, 40.8, 42.7, 45.3, 45.4,
53.5, 58.0, 66.1, 70.0, 97.9, 98.0, 99.2, 99.3, 139.4,
139.8, 157.3, 157.6, 162.9, 163.2; in DMSO-d6: 11.9,
18.5, 20.7, 23.0, 23.6, 23.8, 24.6, 25.7, 26.0, 26.3 (2C),
27.9 (2C), 29.0, 29.9, 34.1, 34.2, 34.7, 37.1, 37.7, 38.5,
42.1, 45.0, 45.8, 53.0, 57.1, 65.0, 69.4, 95.9, 96.0, 98.9,
99.2, 139.2, 139.3, 157.6, 157.8, 162.3, 162.6; two
carbon signals were overlapped by the CD3 multiplet
of the solvent. MALDI-TOF mass spectrum: m/z 644.4
[M + H]+.
13
spectrum (CDCl3), δC, ppm: 12.1 (2C), 18.7 (2C), 21.1
(2C), 23.8 (2C), 24.3 (2C), 24.9 (2C), 25.8 (2C), 26.3
(2C), 26.7 (2C), 28.3 and 28.4 (2C), 30.7 (2C), 32.2
and 32.3 (2C), 34.9 (2C), 35.7 (4C), 37.2 (2C), 38.3
and 38.5 (2C), 40.0 (4C), 40.3 (4C), 42.7 (2C), 48.3–
48.7 m (4C), 56.1–56.7 m (4C), 66.5 and 66.6 (2C),
70.5 (2C), 96.6–100.9 m (8C), 139.9–140.6 m (4C),
156.5–156.7 m (4C), 162.6 (2C), 163.2 (2C). MALDI-
TOF mass spectrum: m/z 1231.9 [M + H]+.
Cyclic dimer VIIc was isolated in addition to com-
pound VIc from the same reaction mixture using
CH2Cl2–MeOH (3:1) as eluent. Yield 29 mg (12%),
Cyclic oligomer mixture VIIb/VIIIb/IXb was
isolated as a separate fraction in the synthesis of dimer
VIIb using CH2Cl2–MeOH–aq. NH3 (100:20:3) as
eluent. Yield 114 mg (46%), light yellow oily sub-
1
light yellow oily substance. H NMR spectrum, δ,
ppm: in CDCl3: 0.63 s (6H), 0.94 br.s (12H), 0.96–
2.01 m (56H), 2.10 br.s (8H), 2.98 br.s (8H), 3.31–
3.45 m (8H), 4.02 br.s (4H), 5.01 s and 5.05 s (2H),
5.90 (4H, 3J = 8.1 Hz), 5.94 d (4H, 3J = 8.6 Hz), 7.20–
7.27 m (4H); signals from six NH protons were not as-
signed unambiguously; in DMSO-d6: 0.58 s and 0.60 s
(6H), 0.98 br.s (12H), 0.95–2.01 m (64H), 2.80 br.s
(8H), 3.24 br.s (8H), 4.08 br.s (4H), 5.15 br.s (2H),
1
stance. H NMR spectrum (CDCl3), δ, ppm: 0.63 s
(3nH), 0.93 br.s (6nH), 0.95–2.01 m (28nH), 3.02 br.s
(4nH), 3.51 br.s (4nH), 4.02 br.s (2nH), 4.41 br.s
(2nH), 5.05 br.s (nH), 5.92 br.s (4nH), 7.22 br.s (2nH);
signals from 2n NH protons were not assigned unam-
13
biguously. C NMR spectrum (CDCl3), δC, ppm: 12.1
(nC), 18.6 (nC), 21.1 (nC), 23.8 (nC), 24.2 (nC), 24.9
(nC), 25.8 (nC), 26.2 (nC), 26.6 (nC), 28.3 (nC), 30.7
(nC), 32.1 (nC), 34.8 (nC), 35.6 (2nC), 37.1 (nC), 39.9
(2nC), 40.2 (3nC), 42.7 (nC), 48.5 (2nC), 56.2 (nC),
56.6 (nC), 66.4 (nC), 70.5 (nC), 96.6–99.4 m (4nC),
139.9 (2nC), 157.2 (nC), 157.3 (nC), 162.7 (nC), 163.3
(nC); n = 2 (VIIb), 3 (VIIIb), 4 (IXb). MALDI-TOF
mass spectrum: m/z 1847.4 [M + H]+ (VIIIb), 2462.9
[M + H]+ (IXb).
3
3
5.77 d (4H, J = 7.7 Hz), 5.94 d (2H, J = 8.0 Hz),
5.96 d (2H, 3J = 7.8 Hz), 6.60–6.67 m (4H), 7.19 t (2H,
3J = 7.5 Hz), 7.21 t (2H, J = 7.5 Hz); signals from
3
two NH protons were not assigned unambiguously.
13C NMR spectrum, δC, ppm: in CDCl3: 12.1 (2C),
18.6 (2C), 21.1 (2C), 23.8 (2C), 24.2 (2C), 24.9 (2C),
25.8 (2C), 26.2 (2C), 26.6 (2C), 28.2 (2C), 28.3 (2C),
30.7 (4C), 32.1 (2C), 34.8 (2C), 35.6 (4C), 37.2 (2C),
38.0 + 38.4 (2C), 39.7 (2C), 40.0 (2C), 40.3 (4C), 42.7
(2C), 45.3 (2C), 45.4 (2C), 56.1–56.7 m (4C), 66.7–
66.9 (2C), 70.7 (2C), 95.6–100.7 m (8C), 140.0
(4C), 157.6–158.1 m (4C), 162.8 (2C), 163.4 (2C); in
DMSO-d6: 11.9 (2C), 18.5 (2C), 20.7 (2C), 23.4 (2C),
23.7 (2C), 24.6 (2C), 25.2 (2C), 25.6 (2C), 25.8 (2C),
26.2 (2C), 27.9 (2C), 28.6 (2C), 30.3 (2C), 30.5 (2C),
31.8 (2C), 34.4 (2C), 34.9 (2C), 35.2 (2C), 36.9 (2C),
38.0 (4C), 42.2 (2C), 45.1 (4C), 55.6 and 55.7 (2C),
56.1 and 56.2 (2C), 65.1 (2C), 69.1 and 69.2 (2C), 96.0
and 96.1 (4C), 99.2 (4C), 139.3 (4C), 157.7 (4C),
162.1 (2C), 162.7 (2C); signals from four carbon atoms
were overlapped by the CD3 multiplet of the solvent.
MALDI-TOF mass spectrum: m/z 1288.0 [M + H]+.
Macrocyclic compound VIc was synthesized from
0.37 mmol (216 mg) of compound IV and 0.37 mmol
(48 mg) of triamine Vc. Eluent CH2Cl2–MeOH (3:1).
Yield 22 mg (9%), light yellow oily substance.
1H NMR spectrum, δ, ppm: in CDCl3: 0.63 s (3H),
3
0.92 d (3H, J = 6.2 Hz), 0.93 s (3H), 0.98–2.00 m
(28H), 2.10 br.s (4H), 2.98 br.s (4H), 3.40–3.50 m
3
(4H), 4.05–4.28 m (2H), 5.30 s (1H), 5.83 d (1H, J =
3
3
7.8 Hz), 5.90 d (1H, J = 8.1 Hz), 6.01 d (1H, J =
3
7.4 Hz), 6.02 d (1H, J = 7.3 Hz), 7.16–7.26 m (2H);
signals from three NH protons were not assigned un-
ambiguously; in DMSO-d6: 0.58 s (3H), 0.87 br.s (6H),
0.92–2.00 m (32H), 2.93 br.s (4H), 3.29 br.s (4H),
3
4.12–4.30 m (2H), 5.31 s (1H), 5.76 d (1H, J =
3
3
7.9 Hz), 5.79 d (1H, J = 8.0 Hz), 5.92 d (1H, J =
3
3
7.9 Hz), 6.03 d (1H, J = 7.8 Hz), 6.49 t (1H, J =
Cyclic oligomer mixture VIIc/VIIIc/IXc was
isolated as a separate fraction in the synthesis of com-
pound VIc. Eluent CH2Cl2–MeOH–aq. NH3 (100:20:1
to 100:20:3). Yield 81 mg (33%), light yellow oily
3
3
4.6 Hz), 6.77 t (1H, J = 5.6 Hz), 7.18 t (1H, J =
7.8 Hz), 7.24 t (1H, 3J = 7.9 Hz; one NH proton signal
13
was not assigned unambiguously. C NMR spectrum,
1
δC, ppm: in CDCl3: 12.1, 18.6, 21.1, 23.5, 24.2, 25.0,
substance. H NMR spectrum, δ, ppm: in CDCl3:
26.1, 26.2, 26.6, 28.4, 28.5, 28.9, 30.2, 30.5, 30.7, 34.4,
0.64 s, 0.66 s, and 0.67 s (3nH); 0.90–0.96 m (6nH);
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AVERIN et al.
84
0.97–2.01 m (28nH); 2.12 br.s (4nH); 2.98 br.s (4nH);
3.40–3.53 m (4nH); 4.03 br.s (2nH); 4.99 s and 5.05 s
Macrocyclic compounds VIe was synthesized
from 0.45 mmol (264 mg) of compound IV and
0.45 mmol (85 mg) of tetraamine Ve. Eluent CH2Cl2–
MeOH–aq. NH3 (100:20:1 to 100:20:3). Yield 91 mg
(29%), light yellow oily substance. 1H NMR spectrum,
3
3
(nH); 5.92 d (nH, J = 7.7 Hz); 5.94 d (nH, J =
7.6 Hz); 5.95–6.04 m (2nH); 7.22–7.31 m (2nH); sig-
nals from 3n NH protons were not assigned unambigu-
ously; in DMSO-d6: 0.58 s and 0.60 s (3nH), 0.89 br.s
(6nH), 0.92–2.00 m (32nH), 2.84 br.s (4nH), 3.25 br.s
(4nH), 4.08 br.s (2nH), 5.15 br.s (nH), 5.77 d (2nH,
3
δ, ppm: in CDCl3: 0.63 s (3H), 0.92 d (3H, J =
6.8 Hz), 0.94 s (3H), 0.96–2.15 m (34H), 2.78–2.95 m
(8H), 3.35–3.50 m (4H), 4.08 br.s (2H), 4.14–4.28 m
3
3
3J = 5.2 Hz), 5.94 d (nH, J = 8.0 Hz), 5.96 d (nH,
(2H), 5.30 s (1H), 5.84 d (1H, J = 7.6 Hz), 5.93 d
3J = 8.1 Hz), 6.65 br.s (2nH), 7.15–7.24 m (2nH);
n = 2 (VIIc), 3 (VIIIc), 4 (IXc). MALDI-TOF mass
spectrum: m/z 1931.6 [M + H]+ (VIIIc), 2575.1
[M + H]+ (IXc).
(1H, 3J = 7.8 Hz), 5.96 d (2H, 3J = 7.6 Hz), 7.23 t (1H,
3J = 7.8 Hz), 7.25 t (1H, 3J = 7.6 Hz); signals from two
NH protons were not assigned unambiguously; in
DMSO-d6: 0.58 s (3H), 0.88 br.s (6H), 0.98–2.01 m
(28H), 1.80 br.s (6H), 2.65–2.90 m (8H), 3.16 br.s
Macrocyclic compound VId was synthesized from
0.51 mmol (298 mg) of compound IV and 0.51 mmol
(89 mg) of tetraamine Vd. Eluent CH2Cl2–MeOH–aq.
NH3 (10:3:1). Yield 25 mg (7%), light yellow oily
3
(4H), 4.16 br.s (2H), 5.26 s (1H), 5.76 d (2H, J =
3
3
6.9 Hz), 5.92 d (1H, J = 7.5 Hz), 5.98 d (1H, J =
7.8 Hz), 6.60 br.s (1H), 6.69 br.s (1H), 7.17 t (1H, 3J =
7.9 Hz), 7.21 t (1H, 3J = 7.9 Hz; signals from two NH
1
substance. H NMR spectrum (CDCl3), δ, ppm: 0.62 s
13
protons were not assigned unambiguously. C NMR
(3H), 0.92 br.s (6H), 0.95–2.01 m (32H), 2.81 br.s
(4H), 2.91 br.s (4H), 3.23 br.s (4H), 4.05–4.28 m (2H),
spectrum, δC, ppm: in CDCl3: 12.0, 18.8, 21.1, 23.0,
23.6, 24.1, 25.5, 26.3, 26.4, 27.7, 27.9, 28.2, 30.5, 31.0
(2C), 32.1, 34.2, 34.6, 35.3, 37.1, 39.0, 39.5, 40.3
(2C), 42.5, 46.6, 46.8, 46.9, 47.0, 53.9, 57.2, 66.3,
69.7, 97.2, 98.2, 98.6, 99.0, 139.5, 139.7, 157.5, 157.6,
162.8, 163.1; in DMSO-d6: 11.8, 18.7, 20.7, 22.9, 23.6,
23.7, 24.7, 24.8, 25.7, 26.1, 27.4 (2C), 27.9, 30.1, 30.7,
30.9, 33.8, 34.3, 35.0, 37.0, 38.0, 38.5, 42.1, 45.1,
45.7, 45.8, 46.1, 53.7, 56.2, 65.2, 69.1, 95.5, 96.1,
99.2, 99.3, 139.3 (2C), 157.7, 157.8, 162.2, 162.5;
signals from two carbon atoms were overlapped by the
CD3 multiplet of the solvent. MALDI-TOF mass spec-
trum: m/z 701.4 [M + H]+.
3
5.30 br.s (2H), 5.31 s (1H), 5.82 d (1H, J = 8.1 Hz),
3
3
5.91 d (1H, J = 8.7 Hz), 5.94 d (1H, J = 8.7 Hz),
3
6.01 d (1H, J = 7.6 Hz), 7.17–7.25 m (2H); signals
from two NH protons were not assigned unambiguous-
ly. 13C NMR spectrum (CDCl3), δC, ppm: 12.1, 18.7,
21.1, 23.7, 24.1, 24.5, 25.3, 26.3, 26.6, 28.0, 28.9,
29.2, 30.7 (2C), 32.0, 34.3, 34.7, 35.3, 37.0, 39.5, 40.0,
40.4, 40.8, 42.5, 46.7, 47.0, 47.2, 47.3, 53.5, 57.5,
66.3, 69.7, 97.5, 98.6, 98.8, 99.2, 139.5, 139.6, 157.8,
157.9, 163.0, 163.1. MALDI-TOF mass spectrum:
m/z 686.6 [M]+.
Cyclic dimer VIId was isolated as the second
product in the synthesis of compound VId. Eluent
CH2Cl2–MeOH–aq. NH3 (10 : 3 : 1). Yield 69 mg
Cyclic dimer VIIe was isolated from the second
fraction in the synthesis of compound VIe. Eluent
CH2Cl2–MeOH–aq. NH3 (10 :3:1). Yield 209 mg
(66%), light yellow oily substance. 1H NMR spectrum,
1
(19%), light yellow oily substance. H NMR spectrum
3
(CDCl3), δ, ppm: 0.62 s (6H), 0.92 br.s (12H), 0.95–
2.00 m (64H), 2.81 br.s (8H), 2.91 br.s (8H), 3.32 br.s
(8H), 4.05 br.s (4H), 5.09 br.s (2H), 5.30 br.s (4H),
δ, ppm: in CDCl3: 0.64 s (6H), 0.91 d (6H, J =
6.3 Hz), 0.94 s (6H), 0.95–2.00 m (68H), 2.77–2.90 m
3
(16H), 3.33 q (8H, J = 5.9 Hz), 3.60 br.s (4H),
3
3
5.91 d (4H, J = 8.7 Hz), 5.94 d (4H, J = 8.7 Hz),
4.09 br.s (4H), 5.13 s (2H), 5.91–5.99 m (8H), 7.24–
7.29 m (4H); signals from four NH protons were not
assigned unambiguously; in DMSO-d6: 0.58 s (6H),
0.87 br.s (12H), 0.90–2.02 m (68H), 2.75–3.00 m
(16H), 3.24 br.s (8H), 4.07 br.s (4H), 5.13 s (2H),
5.76 br.s (4H), 5.96 br.s (4H), 6.59 br.s (4H), 7.19 br.s
(4H); signals from four NH protons were not assigned
unambiguously. 13C NMR spectrum (DMSO-d6), δC,
ppm: 11.9 (2C), 18.5 (2C), 23.0 (2C), 23.4 (2C), 23.7
(2C), 24.6 (2C), 25.3 (2C), 25.9 (2C), 26.1 (2C), 26.2
(2C), 27.8 (2C), 27.9 (2C), 28.6 (2C), 30.5 (2C), 30.6
(2C), 31.9 (2C), 34.5 (2C), 35.1 (2C), 35.2 (2C), 36.5
7.17–7.27 m (4H); signals from four NH protons
13
were not assigned unambiguously. C NMR spectrum
(CDCl3), δ, ppm: 12.1 (2C), 18.7 (2C), 21.1 (2C), 23.9
(2C), 24.2 (2C), 25.0 (2C), 25.8 (2C), 26.3 (2C), 26.7
(2C), 28.3 (2C), 30.2–30.5 m (4C), 30.7 (2C), 32.2
(2C), 34.9 (2C), 35.7 (4C), 37.2 (2C), 40.0 (4C), 40.3
(4C), 40.4 (2C), 42.7 (2C), 46.5–47.7 m (8C), 55.2
(2C), 56.6 (2C), 66.5 (2C), 70.5 (2C), 96.0–99.5 m
(8C), 139.8 (2C), 140.0 (2C), 157.8 (2C), 157.9 (2C),
162.8 (2C), 163.5 (2C). MALDI-TOF mass spectrum:
m/z 1373.1 [M]+.
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SYNTHESIS OF NITROGEN- AND OXYGEN-CONTAINING MACROCYCLES
85
(2C), 38.0 (4C), 42.3 (2C), 44.5 (2C), 44.7 (2C), 44.8
(2C), 45.2 (2C), 55.7 (2C), 56.0 (2C), 65.2 (2C), 69.3
(2C), 95.4 (2C), 96.3 (2C), 99.0 (4C), 139.4 (4C),
157.7 (4C), 162.2 (2C), 162.8 (2C); signals from four
carbon atoms were overlapped by the CD3 multiplet of
the solvent. MALDI-TOF mass spectrum: m/z 1402.2
[M + H]+.
6.0 Hz), 0.95 s (3nH), 0.99–2.00 m (28nH), 3.45 br.s
(4nH), 3.64 s (4nH), 3.67 br.s (4nH), 4.12 br.s (2nH),
3
4.79 br.s (2nH), 5.20 br.s (nH), 5.86 d (nH, J =
3
3
7.7 Hz), 5.90 d (nH, J = 7.8 Hz), 5.98 d (2nH, J =
7.7 Hz), 7.29 t (2nH, 3J = 7.7 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 12.0 (nC), 18.6 (nC), 21.1 (nC),
23.8 (nC), 24.2 (nC), 24.9 (nC), 25.7 (nC), 26.3 (nC),
26.6 (nC), 28.3 (nC), 30.6 (nC), 30.7 (nC), 21.1 (nC),
34.8 (nC), 35.5 (nC), 35.6 (nC), 37.1 (nC), 39.9 (nC),
40.3 (nC), 41.7 (2nC), 42.7 (nC), 56.1 (nC), 56.6 (nC),
66.2 (nC), 69.9 (2nC), 70.2 (3nC), 97.3 (2nC), 98.0
(nC), 98.5 (nC), 139.7 (nC), 139.8 (nC), 157.6 (2nC),
162.8 (nC), 163.4 (nC); n = 2 (VIIg), 3 (VIIIg).
MALDI-TOF mass spectrum: m/z 1321.2 [M]+ (VIIg),
1981.6 [M]+ (VIIIg).
Cyclic dimer VIIf was obtained from 0.55 mmol
(322 mg) of compound IV and 0.55 mmol (122 mg) of
diamine Vf. Eluent CH2Cl2–MeOH (200:1 to 100:1).
Yield 59 mg (15%), light yellow oily substance.
1H NMR spectrum (CDCl3), δ, ppm: 0.64 s (6H),
3
0.92 d (6H, J = 6.2 Hz), 0.96 s (6H), 1.00–2.03 m
(88H), 2.04 s (4H), 3.19 br.s (8H), 4.09–4.16 m (4H),
3
4.23 br.s (4H), 5.15 s (2H), 5.85 d (2H, J = 8.0 Hz),
5.88 d (2H, 3J = 7.9 Hz), 5.97 d (4H, 3J = 7.8 Hz), 7.30 t
Macrocyclic compound VIh was synthesized from
0.51 mmol (298 mg) of compound IV and 0.51 mmol
(105 mg) of diamine Vh. Eluent CH2Cl2–MeOH
(200:1). Yield 82 mg (22%), light yellow oily sub-
3
3
13
(2H, J = 7.9 Hz), 7.31 t (2H, J = 7.8 Hz). C NMR
spectrum (CDCl3), δC, ppm: 12.1 (2C), 18.7 (2C), 21.1
(2C), 23.9 (2C), 24.3 (2C), 25.0 (2C), 25.8 (2C), 26.3
(2C), 26.7 (2C), 28.3 (2C), 29.0 (4C), 30.8 (4C), 32.2
(2C), 32.7 (4C), 34.9 (2C), 35.6 (2C), 35.7 (2C), 36.5
(2C), 37.2 (6C), 40.0 (2C), 40.3 (2C), 42.0 (8C), 42.8
(2C), 43.7 (4C), 47.7 (2C), 56.3 (2C), 56.7 (2C), 66.2
(2C), 70.4 (2C), 96.7 (2C), 97.2 (2C), 97.3 (2C),
98.2 (2C), 139.9 (4C), 157.8 (2C), 157.9 (2C), 162.9
(2C), 163.5 (2C). MALDI-TOF mass spectrum:
m/z 1469.4 [M]+.
1
stance. H NMR spectrum (CDCl3), δ, ppm: 0.64 s
3
(3H), 0.92 d (3H, J = 6.8 Hz), 0.95 s (3H), 0.99–
3
2.05 m (36H), 3.25–3.48 m (8H), 3.55 t (4H, J =
6.2 Hz), 4.12–4.20 m (1H), 4.25–4.33 m (1H),
4.43 br.s (1H), 5.00 br.s (1H), 5.30 s (1H), 5.80 d (1H,
3J = 7.7 Hz), 5.91 d (1H, 3J = 7.8 Hz), 5.95 d (1H, 3J =
3
3
7.9 Hz), 5.96 d (1H, J = 7.7 Hz), 7.28 t (2H, J =
7.8 Hz). 13C NMR spectrum (CDCl3), δC, ppm: 12.0,
18.7, 21.1, 22.7, 23.8, 24.1, 25.2, 26.2, 26.4, 26.8, 26.9,
28.1, 29.3, 29.7, 30.3, 30.7, 30.9, 34.3, 34.7, 35.4, 37.2,
39.4, 40.3, 40.4, 41.6, 42.3, 53.8, 57.3, 66.4, 69.1, 69.6,
70.7, 71.0, 71.2, 96.4, 97.9, 98.2, 98.6, 139.6, 139.7,
157.6, 157.8, 162.8, 163.1. MALDI-TOF mass spec-
trum: m/z 716.7 [M]+.
Macrocyclic compound VIg was synthesized from
0.47 mmol (275 mg) of compound IV and 0.47 mmol
(70 mg) of diamine Vg. Eluent CH2Cl2–MeOH
(200:1). Yield 18 mg (6%), light yellow substance.
1H NMR spectrum (CDCl3), δ, ppm: 0.64 s (3H),
3
0.94 d (3H, J = 7.0 Hz), 0.95 s (3H), 0.99–2.05 m
Cyclic dimer VIIh was isolated from the second
fraction in the synthesis of compound VIh. Eluent
CH2Cl2–MeOH (200 :1). Yield 42 mg (12%), light
3
(28H), 3.40–3.48 m (2H), 3.58 q (2H, J = 4.9 Hz),
3.61–3.72 m (8H), 4.07–4.17 m (1H), 4.28–4.34 m
3
(1H), 4.36 br.s (1H), 4.67 t (1H, J = 4.8 Hz), 5.35 s
1
yellow oily substance. H NMR spectrum (CDCl3), δ,
3
3
(1H), 5.87 d (1H, J = 7.5 Hz), 5.94 d (1H, J =
3
ppm: 0.64 s (6H), 0.93 d (6H, J = 5.9 Hz), 0.96 s
3
3
8.1 Hz), 5.96 d (1H, J = 7.8 Hz), 5.98 d (1H, J =
(6H), 1.00–2.02 m (72H), 3.32 br.s (8H), 3.44 br.s
(8H), 3.52 br.s (8H), 4.13 t (3J = 6.4 Hz) and 4.15–
4.25 m (4H), 4.67 br.s (4H), 5.16 s and 5.21 s (2H),
3
3
7.9 Hz), 7.24 t (1H, J = 8.0 Hz), 7.28 t (1H, J =
7.9 Hz). 13C NMR spectrum (CDCl3), δC, ppm: 12.1,
18.6, 21.2, 22.6, 23.5, 24.0, 25.3, 26.0, 26.2, 28.3, 30.0,
30.3, 31.3, 34.5 (2C), 35.2, 37.2, 40.6, 40.7, 41.2, 41.4,
42.5, 53.4, 58.0, 66.3, 70.1, 70.2, 70.3, 70.5, 70.7, 98.2,
98.3, 98.6, 98.7, 139.5, 139.7, 157.1, 157.4, 163.0,
163.1. MALDI-TOF mass spectrum: m/z 660.7 [M]+.
3
3
5.85 d (2H, J = 7.4 Hz), 5.89 d (2H, J = 8.4 Hz),
3
3
5.96 d (4H, J = 7.8 Hz), 7.28 t (2H, J = 7.6 Hz),
7.30 d (2H, 3J = 7.7 Hz). 13C NMR spectrum (CDCl3),
δC, ppm: 12.0 (2C), 18.6 (2C), 21.1 (2C), 23.8 (2C),
24.2 (2C), 25.0 (2C), 25.7 (2C), 26.2 (2C), 26.5 (4C),
26.6 (2C), 28.3 (2C), 29.4 (4C), 30.7 (4C), 32.1 (2C),
34.9 (2C), 35.5 (2C), 35.6 (2C), 37.1 (2C), 40.0 (2C),
40.1 (2C), 40.2 (2C), 40.3 (2C), 42.7 (2C), 56.1 and
56.2 (2C), 56.7 (2C), 66.1 (2C), 69.1 (2C), 69.2 (2C),
70.1 and 70.3 (2C), 70.8 (4C), 96.8 and 96.9 (2C), 97.1
Cyclic oligomer mixture VIIg/VIIIg was isolated
as a separate fraction in the synthesis of compound
VIg. Eluent CH2Cl2–MeOH (200 :1). Yield 42 mg
1
(14%), light yellow oily substance. H NMR spectrum
3
(CDCl3), δ, ppm: 0.64 s (3nH), 0.92 d (3nH, J =
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AVERIN et al.
86
and 97.2 (4C), 98.0 and 98.3 (2C), 139.7 and 139.8
(4C), 157.9 (4C), 162.8 (2C), 163.4 (2C). MALDI-
TOF mass spectrum: m/z 1433.3 [M]+.
Properties”) and by the Russian Foundation for Basic
Research (project nos. 06-03-32376, 07-03-00619, 08-
03-91308-Ind).
Macrocyclic compound VIi was synthesized from
0.38 mmol (222 mg) of compound IV and 0.38 mmol
(84 mg) of diamine Vi. Eluent CH2Cl2–MeOH
(100:1). Yield 58 mg (21%), light yellow oily sub-
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stance. H NMR spectrum (CDCl3), δ, ppm: 0.64 s
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(3H), 0.91 d (3H, J = 6.7 Hz), 0.95 s (3H), 1.00–
2.01 m (28H), 1.87 quint (2H, 3J = 6.1 Hz), 1.91 quint
3
3
(2H, J = 6.3 Hz), 3.33 br.s (2H), 3.38 q (2H, J =
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3
(1H), 5.81 d (1H, J = 7.9 Hz), 5.89 d (1H, J =
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7.8 Hz), 7.26 t (1H, J = 7.9 Hz), 7.28 t (1H, J =
7.9 Hz). 13C NMR spectrum (CDCl3), δC, ppm: 12.0,
18.7, 21.1, 23.0, 23.7, 24.1, 25.1, 26.1, 26.4, 28.0, 29.4,
29.5, 30.4, 30.9, 31.0, 34.4, 34.7, 35.4, 37.2, 39.3, 40.2,
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Cyclic dimer VIIi was isolated from the second
fraction in the synthesis of compound VIi. Eluent
CH2Cl2–MeOH (100 :1). Yield 28 mg (10%), light
1
p. 6114.
yellow oily substance. H NMR spectrum (CDCl3), δ,
3
12. Nair, V. and Prabhakaran, J., Synth. Commun., 1996,
ppm: 0.64 s (6H), 0.92 d (6H, J = 6.2 Hz), 0.95 s
3
vol. 26, p. 697.
(6H), 0.99–2.00 m (64H), 3.32 q (8H, J = 6.9 Hz),
3
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3.52–3.67 m (24H), 4.12 t (4H, J = 5.6 Hz), 4.71 br.s
(4H), 5.19 s (2H), 5.86 d (2H, 3J = 7.9 Hz), 5.89 d (2H,
3J = 8.0 Hz), 5.95 d (4H, 3J = 7.8 Hz), 7.27 t (2H, 3J =
7.7 Hz), 7.28 t (2H, 3J = 8.0 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 12.1 (2C), 18.6 (2C), 21.1 (2C),
23.8 (2C), 24.2 (2C), 25.0 (2C), 25.7 (2C), 26.3 (2C),
26.6 (2C), 28.3 (2C), 29.3 (4C), 30.7 (4C), 32.1 (2C),
34.9 (2C), 35.6 (2C), 35.7 (2C), 37.1 (2C), 39.7 (2C),
39.8 (2C), 40.0 (2C), 40.3 (2C), 42.7 (2C), 56.2 (2C),
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97.0 (4C), 97.1 (2C), 97.5 (2C), 139.8 (4C), 157.9
(4C), 162.8 (2C), 163.4 (2C). MALDI-TOF mass spec-
trum: m/z 1465.3 [M]+.
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This study was performed under financial support
by the Russian Academy of Sciences (program no. P-8
“Development of Methodology of Organic Synthesis
and Design of Compounds with Practically Important
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009