Synthesis and duplex formation of the reverse amidohelicene tetramer

Article abstract of DOI:10.1016/j.tet.2011.05.059

The reverse amidohelicene (P)-tetramer containing (P)-helicenediamine and m-phenylenedicarboxylate was synthesized. The circular dichroism (CD) and vapor pressure osmometry (VPO) analysis revealed the dimeric aggregate formation in THF. It is notable that

Full text of DOI:10.1016/j.tet.2011.05.059

Tetrahedron 67 (2011) 5477e5486
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and duplex formation of the reverse amidohelicene tetramer
Wataru Ichinose a, Masamichi Miyagawa a, Jun Ito a, Masanori Shigeno a, Ryo Amemiya a,
,b,
Masahiko Yamaguchi a
*
a Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
b WPI Research Center, Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 April 2011
Received in revised form 12 May 2011
Accepted 12 May 2011
Available online 19 May 2011
The reverse amidohelicene (P)-tetramer containing (P)-helicenediamine and m-phenylenedicarboxylate
was synthesized. The circular dichroism (CD) and vapor pressure osmometry (VPO) analysis revealed the
dimeric aggregate formation in THF. It is notable that the reverse amide tetramer formed a duplex, as
well as the original amidohelicene oligomers. In various solutions, mixtures of the reverse (P)-tetramer
and amidohelicene (P)/(M)-tetramer formed homoaggregates instead of heteroaggregates.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Helicene
Aromatic amide
Oligomer
Duplex formation
Molecular recognition
1. Introduction
interesting to examine their derivatives in order to clarify the
relationship between the structure and aggregation property.
Synthetic aromatic amide oligomers have attracted interest in
regard to the formation of ordered structures, such as zipperlike
duplex, double helix, and single helix. The reported compounds
include oligoamidopyridines,1 methoxybenzamide oligomers,2
dianilinocyclohexyl m-phenylenedicarbonyl oligomers,3 N-methyl
pyridinecarboxylate amide oligomers,4 anthranilamide oligomers,5
and phenanthrolinedicarboxyl m-diaminophenylene oligoamides.6
Some of the compounds exhibit structural changes in response to
a change in the environment.1,2,5,6 In general, these synthetic
oligomers are achiral, and optically active compounds have not
been studied except for an optically active oligophenanthroline
possessing one asymmetric carbon atom.6
In this study, we synthesized the reverse amidohelicene oligo-
mers (P)-1, (P)-2, and (P)-3, as an analog of the amidohelicene
oligomers. The arrangement of amine and carbonyl groups were
reverted from the original oligomers (P)-4 to (P)-7. The reversed
oligomers (P)-1 to (P)-3 were synthesized from 1,12-dimethylbenzo
[c]phenanthrene-5,8-diamine8 and isophthalate. The tetramer (P)-
3 formed a duplex in THF, and was a random-coil in DMSO. The
duplex structure of (P)-3 was more stable than that of (P)-5 in THF.
The tetramer (P)-3 did not form heteroaggregates with either (P)-5
or (M)-5, and homoaggregate formation prevailed.
Such study to compare amide oligomers with the reversed
amide structure was reported in the case of natural oligopeptides
and peptide nucleic acid (PNA) oligomers but not for aromatic
amide oligomers. An exception is the oligomer containing m-ben-
zenedicarboxylate and aminoacetylaniline, and its reverse oligo-
mers containing m-benzenediamine and benzoylaminoacetate.9 In
CDCl3, the amide and the reverse amide oligomers formed a het-
eroduplex. A systematic study to compare the properties of the
reversed amide compounds is interesting.
We previously synthesized optically active amidohelicene oligo-
mers
containing
(P)-1,12-dimethylbenzo[c]phenanthrene-5,8-
dicarboxylate and m-phenylenediamine.7 The amidohelicene
trimer (P)-4 to nonamer (P)-7 formed stable helix dimers in nonpolar
solvents, and the aggregate of (P)-5 in chloroform did not dissociate
between 5 and 60 ꢀC even at the concentration of 5.0ꢁ10ꢂ6 M.
The helix dimer of tetramer (P)-5 dissociated to random-coil in
hydrogen-bond-breaking solvents. It was also observed that the
equilibrated states of the helix dimer and random-coil were not
affected by temperature change. This is a notable aggregation phe-
nomenon of chiral synthetic amide oligomers, and it was considered
2. Result and discussion
2.1. Synthesis
In this study, the reverse amidohelicene oligomers were syn-
thesized by repeating an amide coupling reaction using a building
* Corresponding author. Tel.: þ81 22 795 6812; fax: þ81 22 795 6811; e-mail
address: yama@mail.pharm.tohoku.ac.jp (M. Yamaguchi).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.059

5478
Reverse (P)-amidohelicene Oligomers
W. Ichinose et al. / Tetrahedron 67 (2011) 5477e5486
(Boc)2O
Et3N
+
1,4-dioxane
H2O
Boc
Boc
Boc
N
H
H2N
NH2
H2N
N
H
O
O
N
H
O
O
OBu-t
N
H
N
H
(P)-8
N
H
N
H
t-BuO
(P)-9
(P)-1
11%
63%
2 atoms
R
n-1
HO2C
CO2H
HO2C
CO2H
HO2C
CO2Bn
R = CO2n-C10H21
(P)-1 (n = 1)
(P)-2 (n = 2)
(P)-3 (n = 4)
1) NaHCO3
1) NaHCO3
2) BnBr
CO2H
10
R
11
R
12
2) n-C10H21Br
37%
52%
(P)-Amidohelicene Oligomers
1) KOH
(P)-9
O
ClOC
CO2Bn
O
Bn
O
Boc
N
H
2) SOCl2
DMF
N
H
Pyridine
CHCl2
R
H
H
N
H
N
H
N
R
NHBoc
N
BocHN
(P)-14
87%
13
O
O
O
O
100%
R
R
R
2 atoms
n-1
Pd/C
H2 gas
R = CO2n-C10H21
O
O
1) KOH
O
O
(P)-4 (n = 3)
(P)-5 (n = 4)
(P)-6 (n = 8)
(P)-7 (n = 9)
Boc
Boc
N
H
OH
N
H
N
Cl
N
AcOEt
2) SOCl2
DMF
H
H
R
R
(P)-15
(P)-16
98%
92%
block acid chloride (P)-16 containing a 1,12-dimethylbenzo[c]
phenanthrene moiety and a m-phenylene moiety (Scheme 1). 1,3,5-
Benzenetricarboxylate with three differentiated carboxylates was
synthesized.10 Monosodium salt of 1,3,5-benzenetricarboxylic acid
10 was reacted with 1-bromodecane in DMF at room temperature
giving decyl ester 11 in 37% yield. The treatment of 11 sodium salt
with benzyl bromide gave decyl benzyl ester 12 in 52% yield. Then,
12 was converted to acid chloride 13 with thionyl chloride in 100%
yield.7 An amino group of diaminohelicene (P)-88 was monop-
rotected with di(tert-butoxy)carbonyl anhydride giving carbamate
(P)-9 in 63% yield along with dicarbamate (P)-1 (11%). Coupling of
(P)-9 and 13 gave (P)-14, and removal of the benzyl group gave
carboxylic acid (P)-15. The building block acid chloride (P)-16 was
formed from (P)-15 by treatment of its potassium salt with thionyl
chloride at ꢂ20 ꢀC in 92% yield. The low-temperature conditions
were critical to obtain (P)-16 in high yield. The reverse amide dimer
(P)-2 was synthesized by the reaction (P)-9 and (P)-16 in
dichloromethane in the presence of pyridine in 88% yield. Then,
dimer (P)-2 was deprotected with trifluoroacetic acid giving di-
amine (P)-17, which was coupled with (P)-16 to give the tetramer
(P)-3 in 48% yield. Attempts to synthesize trimer from (P)-8 and (P)-
16 failed, because of the instability of (P)-8 toward air oxidation.10
Higher oligomers could not be obtained because of the low solu-
bility of the deprotected diamine compound from tetramer (P)-3.
(P)-9
CH2Cl2
Pyridine
Coupling with (P)-16
86%
(P)-2 (n = 2)
CF3CO2H
Deprotection
CH2Cl2
O
O
N
NH2
H2N
N
H
H
R
90%
(P)-17
CH2Cl2
Pyridine
Coupling with (P)-16
(P)-3 (n = 4)
48%
R = CO2n-C10H21
Scheme 1.
indicated that the tetramer (P)-3 formed duplex in THF and
random-coil in DMSO. While the 1H NMR spectrum of (P)-3 in
DMSO showed sharp peaks, that in THF was broadened and shifted
to a higher field (Fig. 5).
2.2. Duplex formation
IR analysis of (P)-3 was conducted in solution (1.0ꢁ10ꢂ3 M) at
room temperature. The original (P)-5 is helix dimer in chloroform
as shown by CD and VPO,7 and showed amide IR absorptions at
1654 and 1648 cmꢂ1. In THF, (P)-5 is a random-coil,7 and provided
an amide absorption at 1682 cmꢂ1 (Fig. 6). It is known that
hydrogen-bonded amide carbonyl absorption shifts to lower fre-
The aggregate formation of monomer (P)-1, dimer (P)-2, and
tetramer (P)-3 (5.0ꢁ10ꢂ6 M, 25 ꢀC) in dimethyl sulfoxide (DMSO)
and tetrahydrofuran (THF) was examined by CD (Fig. 1). In DMSO,
the intensity of the Cotton effect increased with the increase in the
helicene numbers. In THF, (P)-1 and (P)-2 showed similar spectra
with those in DMSO, and (P)-3 provided a different spectrum with
a strong positive Cotton effect at 318 nm. UV absorption of (P)-3 in
THF at 309 nm was weaker than that in DMSO, and the absorption
maximum shifted from 309 nm in DMSO to 313 nm in THF (Fig. 2).
The CD and UV spectra in THF did not change by changing the
concentration between 5.0ꢁ10ꢂ5 M and 2.5ꢁ10ꢂ7 M and the tem-
perature between 5 and 60 ꢀC (Figs. 3 and 4, and S1). Vapor pres-
sure osmometry (VPO) study of (P)-3 in THF (1.0ꢁ10ꢂ3 M, 45 ꢀC)
showed bimolecular aggregate (N¼2.2ꢃ0.1) formation. The results
quency by 20e40 cm ,
ꢂ111 and the observations are consistent with
helix dimer formation of (P)-5 by hydrogen-bonding. In THF
(1.0ꢁ10ꢂ3 M), (P)-3 was a pure duplex as indicated by CD and VPO
(Fig. 3, and 4), and showed amide absorptions at 1643 and
1687 cmꢂ1. The duplex of (P)-3 appeared to possess hydrogen-
bonded amides as well as nonhydrogen-bonded amides.
Note that both amidohelicene tetramer (P)-5 and the reverse
amidohelicene tetramer (P)-3 formed dimeric aggregate in solution.
We previously described that optically active acetylene oligomers

W. Ichinose et al. / Tetrahedron 67 (2011) 5477e5486
5479
Fig. 3. (a) CD spectra, (b) UV spectra of tetramer (P)-3 at 25 ꢀC at various concentra-
tions in THF.
Fig. 1. CD spectra (5.0ꢁ10ꢂ6 M, 25 ꢀC) of reverse amidohelicene oligomers: (a) in
DMSO, (b) in THF.
containing helicene and m-phenylene formed double helix in so-
lution.12 All these oligomers possessing two-atom linkages between
helicene and m-phenylene formed dimeric aggregates.
The solvent effect on the aggregate formation was examined by
CD (5.0ꢁ10ꢂ6 M, 25 ꢀC) (Fig. 7). The spectrum of (P)-3 in pyridine
was similar to that in DMSO. In THF/chloroform (70/30) and chlo-
roform/DMSO (95/5), similar spectra to that in THF were obtained.
The CD spectrum, therefore, was considered to be that of pure
duplex. The results also indicated that the driving force of duplex
formation of (P)-3 is hydrogen-bonding. Since the solubility of (P)-3
was low in chloroform and toluene, CD analysis was not conducted
in these solvents.
The CD spectra of (P)-3 in a mixed solvent of THF and DMSO
(5.0ꢁ10ꢂ6 M) were used to obtain the ratio of random-coil to du-
plex (Fig. 8). The CD spectra in DMSO (5.0ꢁ10ꢂ6 M) did not change
between 5 and 60 ꢀC (Fig. 9c), and the same spectra were obtained
in pyridine. The spectrum therefore was considered to be that of
a pure random-coil state. Then, the D3 values at 318 nm for the pure
duplex (þ410 cmꢂ1
M
ꢂ1) and pure random-coil (þ40 cmꢂ1 Mꢂ1
)
were obtained. The ratio of duplex to random-coil of (P)-3 in the
mixed solutions was estimated from the D3 values at 318 nm (Figs.
8e10, and S2). For example, D3 þ339 cmꢂ1 Mꢂ1 at 318 nm was
obtained in THF/DMSO (99/1), from which the equilibrium of (P)-3
between the duplex and random-coil was calculated to be 81/19.
With increasing amount of DMSO, the amount of duplex decreased.
From the results, equilibria of the reversed amidohelicene tetramer
(P)-3 and (P)-5 were compared. In chloroform/DMSO (95/5), the
ratio of duplex to random-coil of (P)-3 was calculated to be 77/23
from the D3 þ325 cmꢂ1 Mꢂ1 (Fig. 10a). Under the same solvent
conditions, (P)-5 was in equilibrium between the helix dimer and
random-coil with a 20/80 ratio.7 In toluene/DMSO (99/1), the
equilibrium ratio of (P)-3 was 75/25 (Fig. 10b), and that of (P)-5 was
5/95.7 The results indicated the stable duplex formation of (P)-3
compared with that of (P)-5.
Fig. 2. UV spectra (5.0ꢁ10ꢂ6 M, 25 ꢀC) of reverse amidohelicene oligomers: (a) in
DMSO, (b) in THF.

5480
W. Ichinose et al. / Tetrahedron 67 (2011) 5477e5486
Fig. 6. IR spectra of (P)-3 and (P)-5 (1.0ꢁ10ꢂ3 M). (a) (P)-3 in THF: duplex, (b) (P)-5 in
chloroform: helix dimer, (c) (P)-5 in THF: random-coil.
Fig. 4. CD spectra of tetramer (P)-3 in THF: (a) 50ꢁ10ꢂ6 M, (b) 5.0ꢁ10ꢂ6 M, (c)
0.25ꢁ10ꢂ6 M.
Fig. 7. CD spectra (5.0ꢁ10ꢂ6 M, 25 ꢀC) of tetramer (P)-3 in various solvents.
and S2). CD spectra were again not affected by the temperature
change in these mixed solvents. An exception was in toluene/DMSO
(99/1) at 100 ꢀC, in which a slight decrease was observed (Fig. 10b).
Both the amidohelicene tetramer (P)-5 and the reverse amido-
helicene tetramer (P)-3 formed duplex in nonpolar solvents and
random-coil in hydrogen-bond-breaking solvents. The equilibrium
between the duplex and random-coil for both (P)-5 and (P)-3 was
also not affected by temperature changes. Different properties were
noted concerning the stability of the duplex. (P)-3 formed a stable
duplex in THF, whereas (P)-5 did not form dimeric aggregate in the
same solvent. Solubility in chloroform also differed. Whereas (P)-5
was soluble in chloroform up to 1.0ꢁ10ꢂ2 M, (P)-3 was not soluble
even at 5.0ꢁ10ꢂ6 M. Both oligomers showed similar CD spectra of
random-coil but different spectra of duplex (Fig. 11), which may be
due to the difference in the three-dimensional structures of (P)-3
and (P)-5. Based on the report that similar linear helicene oligomer
formed helix conformation,7,12 we guess the tetramer (P)-3 have
also helix formation in the aggregations. Direct experimental data
for helix conformation of (P)-3 was not obtained by any analysis in
this paper.
Fig. 5. 1H NMR spectra of tetramer (P)-3 at 1.0ꢁ10ꢂ3 M in DMSO and THF.
The CD study was conducted at different temperatures. In THF at
the concentration between 1.0ꢁ10ꢂ6 and 2.5ꢁ10ꢂ7 M, (P)-3 is a pure
duplex (Figs. 4, and S1). No change in the CD spectrum was observed
between 60 and 5 ꢀC. In DMSO, where (P)-3 was a random-coil, no
temperature effect was observed. In THF/DMSO (99/1, 98/2, 97/3,
95/5), chloroform/DMSO (95/5), and toluene/DMSO (99/1) at
5.0ꢁ10ꢂ6 M, equilibria between the duplex and random-coil were
81/19, 64/36, 20/80, <5/95, 77/23, and 75/25, respectively (Figs. 9,

W. Ichinose et al. / Tetrahedron 67 (2011) 5477e5486
5481
Fig. 8. CD spectra (5.0ꢁ10ꢂ6 M, 25 ꢀC) of tetramer (P)-3 in THF/DMSO at various ratios.
The ratio of duplex to random-coil was also noted.
2.3. Aggregation in mixed systems of (P)-3 and (P)/(M)-5
Since both amidohelicene oligomers and the reverse amidohe-
licene tetramer (P)-3 formed duplex, it was considered interesting
to determine whether they could form heteroaggregates. The re-
versed tetramer (P)-3 and amidohelicene tetramer (P)-5 were
mixed at a 1/1 ratio (each 2.5ꢁ10ꢂ6 M) in various solvents. The
mixture of tetramer (P)-3 and tetramer (P)-5 has the advantage of
being CD active. When a heteroaggregate is formed, the CD spectra
should be different from those obtained by the addition of the
spectrum of each compound in the same solvent. It was also con-
sidered important to control the initial states of both oligomers,
duplex or random-coil, because the initial states can affect the
process of heteroaggregate formation. The mixing experiments
therefore were conducted under different conditions, where dif-
ferent compositions of duplex or random-coil were obtained.
In DMSO, both (P)-3 and (P)-5 were in random-coil states at
5.0ꢁ10ꢂ6 M.7 The solutions were mixed, and the CD spectrum
(each 2.5ꢁ10ꢂ6 M) was obtained. The experimental spectrum
coincided with the calculated spectrum (Fig. 12a), which was
obtained by the addition of the spectra of (P)-3 and (P)-5 in DMSO
at 5.0ꢁ10ꢂ6 M. The results indicated that the mixture of (P)-3 and
(P)-5 in DMSO did not produce aggregates, and both were in
random-coil states. In THF (5.0ꢁ10ꢂ6 M), (P)-5 was random-coil
and (P)-3 formed duplex. The experimental CD spectra (each
2.5ꢁ10ꢂ6 M) obtained by mixing the solutions coincided with the
calculated spectrum (Fig. 12b).
Heteroaggregate formation was examined for equilibrated
mixtures of homoaggregate and random-coil. Under the same
equilibrated conditions, four combinations of interactions between
(P)-3 and (P)-5 can occur, namely, duplex/helix dimer, duplex/
random-coil, random-coil/helix dimer, and random-coil/random-
coil, and the probability of heteroaggregate formation can increase.
In chloroform/DMSO (95/5) at 5.0ꢁ10ꢂ6 M, the equilibrium ratios
between homoduplex and random-coil were 77/23 for (P)-3 and
20/80 for (P)-5. The experimental CD spectrum (each 2.5ꢁ10ꢂ6 M)
in the mixed solution coincided with the calculated spectrum,
which was obtained by adding the CD spectra (5.0ꢁ10ꢂ6 M) of (P)-3
and (P)-5 in the same solvents (Fig. 13a). In toluene/DMSO (99/1),
(P)-3 and (P)-5 showed 75/25 and 5/95 ratios of duplex and
Fig. 9. CD spectra of tetramer (P)-3 at 5.0ꢁ10ꢂ6 M at various temperatures in THF/
DMSO: (a) 100/0, (b) 97/3, (c) 0/100. The ratio of duplex to random-coil was also noted.
random-coil, respectively. The CD spectrum in the mixed solution
again coincided with the calculated one (Fig. 13b). The results in-
dicated that the heteroaggregates of (P)-3 and (P)-5 did not form
under these equilibrium states.
The same mixing experiments using (P)-3 and the enantiomeric
(M)-5 were conducted. In chloroform/DMSO (95/5) and toluene/
DMSO (99/1), the CD spectra showed no sign of heteroaggregate
formation between (P)-3 and (M)-5 (Fig. 14).
Attempts were made to change the solvent ratio. Solutions
containing (P)-3/(P)-5 or (P)-3/(M)-5 in chloroform/DMSO (95/5)
(each 2.5ꢁ10ꢂ6 M) were prepared, and chloroform was evaporated
in vacuo. To the residual DMSO solution was added chloroform
to make a chloroform/DMSO (95/5) solution, and CD spectra were
obtained. The spectra coincided with the calculated one
(5ꢁ10ꢂ6 M) obtained from (P)-3/(P)-5 and (P)-3/(M)-5 (Fig. 15).
The results showed that, in the mixtures of amidohelicene tet-
ramer (P)-5/(M)-5 and the reverse amidohelicene tetramer (P)-3,
homoaggregates prevailed over heteroaggregates (Fig. 16). It may
be noted that (P)-3 recognized (P)-3 as the counterpart rather than
(P)-5 or (M)-5 in these mixed systems. The difference in the relative
three-dimensional arrangement of the hydrogen-bonded second-
ary amides may be playing an important role.

5482
W. Ichinose et al. / Tetrahedron 67 (2011) 5477e5486
Fig. 10. CD spectra of tetramer (P)-3 at 5.0ꢁ10ꢂ6 M at various temperatures: (a) in
DMSO/chloroform 5/95, (b) in DMSO/toluene 1/99. The ratio of duplex to random-coil
was also noted.
Fig. 12. CD spectra of a 1/1 mixture of (P)-3 and (P)-5 (each 2.5ꢁ10ꢂ6 M), (P)-3, and
(P)-5 (5.0ꢁ10ꢂ6 M) in various solvents at 25 ꢀC: (a) DMSO, (b) THF. The spectrum
calculated by adding those of (P)-3 and (P)-5 is also shown.
Fig. 11. CD spectra of (P)-3 and (P)-5 (each 2.5ꢁ10ꢂ6 M) in various solvents at 25 ꢀC.
3. Conclusion
To summarize, the reversed tetramer (P)-3 was synthesized
from 1,12-dimethylbenzo[c]phenanthrene-5,8-diamine and iso-
phthalate. The tetramer (P)-3 formed a duplex in THF, and was
a random-coil in DMSO. The equilibrium between the duplex and
random-coil was not affected by temperature change between 5
and 60 ꢀC. The duplex structure of (P)-3 was stable in THF, whereas
(P)-5 did not form dimeric aggregate in the same solvent. The tet-
ramer (P)-3 did not form heteroaggregates with either (P)-5 or (M)-
5, and formed only homoaggregates.
Fig. 13. CD spectra of a 1/1 mixture of (P)-3 and (P)-5 (each 2.5ꢁ10ꢂ6 M), (P)-3, and (P)-5
(5.0ꢁ10ꢂ6 M) in various solvents at 25 ꢀC: (a) chloroform/DMSO 95/5, (b) toluene/DMSO
99/1. The spectrum calculated by adding those of (P)-3 and (P)-5 is also shown.

W. Ichinose et al. / Tetrahedron 67 (2011) 5477e5486
5483
Fig. 16. Homoaggregation in mixed systems of (P)-3 and (P)/(M)-5.
4. Experimental section
4.1. General methods
Melting points were determined with a Yanagimoto micro
melting point apparatus without correction. Elemental analyses
were conducted with Yanaco CHN CORDER MT-6. Optical rotations
were measured on a JASCO P-1010 digital polarimeter. IR spec-
tra were measured on a JASCO FT/IR-400 spectrophotometer. 1H
NMR and 13C NMR spectra were recorded on a Varian Mercury (1H,
400 MHz; 13C, 100 MHz) with tetramethylsilane as an internal
standard. 1H NMR spectra taken in acetone-d6
2.49), CD3OD ( 3.30), and THF-d8 ( 3.58) were referenced to the
residual solvents. 13C NMR spectra taken in CDCl3 (
77.0), acetone-
d6 ( 206.5), DMSO-d6 ( 39.7), and CD3OD ( 49.0) were referenced
(d 2.04), DMSO-d6
(d
d
d
d
d
d
d
to the residual solvents. Low- and high-resolution mass spectra
were recorded on a JEOL JMS DX-303, or a JEOL JMS AX-700 spec-
trometer. FAB mass spectra were recorded on a JEOL JMS DX-303, or
a JEOL JMS AX-700 spectrometer by using 3-nitrobenzyl alcohol
(NBA) matrix. MALDI-TOF MS spectra were recorded on a Persep-
tive Biosystems VoyagerÔ DE observing with negative ion mode
and using 2-amino-5-nitropyridine as a matrix. CD spectra were
measured on a JASCO J-720 spectropolarimeter. Vapor pressure
osmometry (VPO) was conducted with a KNAUER K-7000 molec-
ular weight apparatus using benzyl as a standard. Gel permeation
chromatography (GPC) was conducted with a Recycling Preparative
HPLC LC-908 or LC-918 (Japan Analytical Industry, Co. Ltd.).
Fig. 14. CD spectra of a 1/1 mixture of (P)-3 and (M)-5 (each 2.5ꢁ10ꢂ6 M), (P)-3, and
(M)-5 (5.0ꢁ10ꢂ6 M) in various solvents at 25 ꢀC: (a) chloroform/DMSO 95/5, (b) tol-
uene/DMSO 99/1. The spectrum calculated by adding those of (P)-3 and (M)-5 is also
shown.
4.2. Synthesis and characterization
4.2.1. (P)-5-Amino-8-(tert-butoxycarbonyl)amino-1,12-dimethylbenzo
[c]phenanthrene, (P)-9 and (P)-5,8-di-(tert-butoxycarbonylamino)-
1,12-dimethylbenzo[c]phenanthrene, (P)-1. To a solution of (P)-5,8-
diamino-1,12-dimethylbenzo[c]phenanthrene8
(226.0
mg,
0.789 mmol) in 1,4-dioxane (3.38 mL) and water (0.56 mL) were
added triethylamine (0.229 mL, 1.64 mmol) and di(tert-butyl)dicar-
bonate (0.217 mL, 0.945 mmol) at 0 ꢀC. The mixture was stirred
vigorously at room temperature for 24 h.13 The reaction was
quenched by adding 10% citric acid, and the organic materials were
extracted with ethyl acetate twice. The combined organic layers were
washed with water twice, brine, and dried over magnesium sulfate.
The solvents were removed in vacuo, and separation by silica gel
chromatography (ethyl acetate/hexane¼1/3) gave (P)-9 (191.5 mg,
63%), (P)-1 (40.8 mg, 0.084 mmol, 11%) and recovered dia-
minohelicene (56.9 mg, 25%).
21
Compound (P)-9. Mp 205e207 ꢀC (hexane/diethyl ether). [
a
]
D
ꢂ430 (c 0.50, CHCl3). LRMS (EI, 70 eV) m/z 386 (Mþ, 18%), 330
t
(Mþꢂ Bu, 41%), 312 (MþꢂOtBu, 40%), 286 (MþꢂBoc, 100%). HRMS
m/z calcd for C25H26N2O2: 386.1993. Found: 386.1992. IR (KBr)
3448, 3369, 2960, 2868, 1709, 1630 cmꢂ1. Anal. (C25H26N2O2) Calcd:
C, 77.69; H, 6.78; N, 7.25%. Found: C, 77.29; H, 6.96; N, 7.17%. 1H NMR
Fig. 15. CD spectra at 25 ꢀC in chloroform/DMSO 95/5: (a) 1/1 mixture of (P)-3 and (P)-
5 (each 2.5ꢁ10ꢂ6 M), (b) 1/1 mixture of (P)-3 and (M)-5 (each 2.5ꢁ10ꢂ6 M). Once their
samples were evaporated in vacuo, they were resolved in the same solvent and ob-
served as gray lines.
(400 MHz, CDCl3)
d 1.59 (9H, s), 1.91 (3H, s), 1.93 (3H, s), 4.35 (2H,
br), 7.00 (2H, s), 7.36 (1H, d, J¼7 Hz), 7.39 (1H, d, J¼7 Hz), 7.49 (1H,
dd, J¼7, 9 Hz) 7.54 (1H, dd, J¼7, 9 Hz), 7.84 (2H, t, J¼9 Hz), 8.07 (1H,
s). 13C NMR (100 MHz, CDCl3)
d 23.5, 23.6, 28.4, 80.7, 107.0, 115.7,

5484
W. Ichinose et al. / Tetrahedron 67 (2011) 5477e5486
117.1, 117.4, 117.9, 124.3, 124.5, 124.7, 128.2, 128.4, 131.7, 132.2, 132.4,
134.0, 136.2, 136.7, 141.3, 153.5.
chloride (0.24 mL) and N,N-dimethylformamide (3 drops) were
added. The mixture was stirred at room temperature for 1 h. Excess
thionyl chloride was removed in vacuo, and the residue was
azeotropically dried twice by adding toluene (1.0 mL) and evapo-
rated in vacuo. The resulted acid chloride 13 (136.8 mg, 100%) was
purified by rapid silica gel chromatography.7 Mp 36e37 ꢀC (hex-
ane). LRMS (EI, 70 eV) m/z 460 (C26H3137ClO5 þ, 10%), 458
Compound (P)-1. Mp 199e200 ꢀC (ethyl acetate). [
a
]
D
21 ꢂ354 (c
0.35, CHCl3). LRMS (EI, 70 eV) m/z 486 (Mþ, 11%), 386 (MþꢂBocþH,
38%). HRMS m/z calcd for C30H34N2O4: 486.2517. Found: 486.2525.
IR (KBr) 3318, 2978, 2868, 1686 cmꢂ1. Anal. (C30H34N2O4) Calcd: C,
74.04; H, 7.05; N, 5.76%. Found: C, 73.90; H, 7.09; N, 5.69%. 1H NMR
(400 MHz, CDCl3)
d
1.59 (18H, s), 1.91 (6H, s), 6.99 (2H, s), 7.39 (2H,
(C26H3135ClO5þ, 26%), 423 (C26H31O5
þ
, 37%), 368 (MþꢂbenzyloxyþH,
d, J¼7 Hz), 7.56 (2H, t, J¼8 Hz) 7.88 (2H, d, J¼8 Hz), 8.21 (2H, s). 13C
49%). HRMS m/z calcd for C26H3135ClO5: 458.1860. Found: 458.1843.
NMR (100 MHz, CDCl3)
d
23.4, 28.3, 80.6, 117.0, 117.6, 120.0, 125.2,
.
IR (neat) 2954, 2925, 2854, 1765, 1733 cmꢂ1 1H NMR (400 MHz,
125.9, 128.2, 131.7 (two peaks), 132.7, 136.7, 153.5.
CDCl3)
d
0.88 (3H, t, J¼7 Hz), 1.27e1.48 (14H, m), 1.81 (2H, quint,
J¼7 Hz), 4.39 (2H, t, J¼7 Hz), 5.44 (2H, s), 7.33e7.48 (5H, m), 8.90
4.2.2. 5-Decyloxycarbonylbenzene-1,3-dicarboxylic acid, 11. A mix-
ture of 1,3,5-benzenetricarboxylic acid 10 (210 mg, 1.0 mmol) and
sodium bicarbonate (84 mg, 1.0 mmol) were suspended in N,N-
dimethylformamide (5 mL), and the mixture was stirred at room
temperature for 12 h. 1-Bromodecane (0.42 mL, 2.0 mmol) was
added, and stirring was continued for another 7 h at 90 ꢀC.10 Then,
aqueous sodium carbonate (212 mg in 25 mL) was added, and the
resulting mixture was extracted three times with diethyl ether. The
organic layers were discarded. The aqueous layer was acidified with
saturated aqueous potassium bisulfate, and extracted three times
with ethyl acetate. The combined organic layers were washed with
water and brine, and dried over magnesium sulfate. The solvents
were removed in vacuo, and separation by silica gel chromatography
(ethyl acetate/hexane¼1/2) gave 11 (128.6 mg, 37%) and recovered
benzenetricarboxylic acid (104 mg, 50%). Mp 194e195 ꢀC (toluene).
LRMS (EI, 70 eV) m/z 350 (Mþ, 1%), 332 (MþꢂH2O, 1%), 211
(MþꢂdecylþH, 100%). HRMS m/z calcd for C19H26O6: 350.1728.
(1H, t, J¼2 Hz), 8.92 (1H, t, J¼2 Hz), 8.97 (1H, t, J¼2 Hz). 13C NMR
(100 MHz, CDCl3) d 14.0, 22.6, 25.9, 28.5, 29.2 (two peaks), 29.4 (two
peaks), 31.8, 66.2, 67.6, 128.4, 128.5, 128.6, 131.8, 132.2, 134.2, 135.1,
135.6, 135.7, 136.4, 164.0, 164.1, 167.0.
4.2.5. (P)-5-{3-(Benzyloxycarbonyl)-5-(decyloxycarbonyl)benzoyla-
mino}-8-(tert-butoxycarbonylamino)-1,12-dimethylbenzo[c]phenan-
threne, (P)-14. Under an argon atmosphere, to a solution of (P)-9
(217 mg, 0.56 mmol) in dichloromethane (50 mL) and pyridine
(0.56 mL) was added acid chloride 13 (319 mg, 0.70 mmol) in
dichloromethane (45 mL), and the mixture was stirred at room
temperature for 12 h. Then, 2 M hydrochloric acid was added, and
the organic materials were extracted with dichloromethane twice.
Thecombinedorganic layers werewashed with waterandbrine, and
dried over magnesium sulfate. Purification by silica gel chroma-
tography (ethyl acetate/hexane¼1/6) gave (P)-14 (394 mg, 87%). Mp
91e94 ꢀC (hexane/THF). [
a
]
D
21 ꢂ242 (c 0.25, CHCl3). MS (FAB, NBA)
Found: 350.1729. IR (KBr) 3084, 2956, 2920, 2852, 1735, 1701 cmꢂ1
Anal. (C19H26O6) Calcd: C, 65.11; H, 7.48%. Found: C, 64.96; H, 7.31%.
1H NMR (400 MHz, CD3OD)
0.88 (3H, t, J¼7 Hz),1.26e1.51 (14H, m),
.
m/z calcd for C51H56N2O7: 808.4084. Found: 808.4075. IR (KBr) 3242,
2954, 2925, 2854, 1728, 1684, 1649, 1523 cmꢂ1. Anal. (C51H56N2O7)
Calcd: C, 75.72; H, 6.98; N, 3.46%. Found: C, 75.54; H, 6.95; N, 3.43%.
d
1.81 (2H, quint, J¼7 Hz), 4.38 (2H, t, J¼7 Hz), 8.80 (2H, d, J¼2 Hz),
1H NMR (400 MHz, acetone-d6)
d
0.84 (3H, t, J¼7 Hz),1.25e1.51 (14H,
8.82 (1H, t, J¼2 Hz). 13C NMR (100 MHz, CD3OD)
d
14.4, 23.7, 27.1,
m),1.55 (9H, s),1.81 (2H, quint, J¼7 Hz),1.91 (3H, s),1.92 (3H, s), 4.39
(2H, t, J¼7 Hz), 5.47 (2H, s), 7.35e7.63 (5H, m), 8.07 (1H, s), 8.08 (1H,
s), 8.18 (1H, d, J¼8 Hz), 8.24 (1H, d, J¼8 Hz), 8.59 (1H, s), 8.80 (1H, s),
8.96 (1H, s), 8.98 (1H, s), 10.21 (1H, s). 13C NMR (100 MHz, CDCl3)
29.7, 30.3, 30.4, 30.6, 33.1, 66.9, 132.7, 133.3, 135.2, 135.7, 166.4, 167.8.
4.2.3. 3-Benzyloxycarbonyl-5-decyloxycarbonyl-1-benzoic acid, 12. A
mixture of 11 (2.42 g, 6.9 mmol) and sodium bicarbonate (580 mg,
6.9 mmol) was suspended in N,N-dimethylformamide (24 mL), and
the mixture was stirred at room temperature for 12 h. Benzyl bro-
mide (1.7 mL, 13.9 mmol) was added, and stirring was continued for
another 2.5 h at 90 ꢀC.10 The reaction was quenched by adding sat-
urated aqueous potassium bisulfate at 0 ꢀC, and the organic materials
were extracted with ethyl acetate twice. The combined organic
layers were washed with water and brine, and dried over magne-
sium sulfate. The solvents were removed in vacuo, and purification
by silica gel chromatography (ethyl acetate/hexane¼1/7) gave 12
(1.58 g, 52%) and recovered 11 (724 mg, 30%). Mp 82 ꢀC (hexane).
LRMS (EI, 70 eV) m/z 440 (Mþ, 35%), 422 (MþꢂH2O, 14%), 333
(Mþꢂbenzyloxy, 100%), 283 (Mþꢂdecyloxy, 30%). HRMS m/z calcd
for C26H32O6: 440.2197. Found: 440.2199. IR (KBr) 3087, 2954, 2924,
2852, 1728, 1697 cmꢂ1. Anal. (C26H32O6) Calcd: C, 70.89; H, 7.32%.
d
14.1, 22.6, 23.4, 23.5, 25.9, 28.3, 28.6, 29.3, 29.5 (two peaks), 31.8,
65.9, 67.3, 80.7, 118.2, 118.3, 118.7, 120.7, 121.6, 125.5, 125.6, 126.8,
126.9,128.4,128.5,128.6,130.7,130.9,131.3,131.6,131.7,132.5,132.7,
133.3, 135.4, 135.5, 136.6, 136.7, 153.9, 164.6, 164.9, 165.1.
4.2.6. (P)-3-(Decyloxycarbonyl)-5-{1,12-dimethyl-8-(tert-butoxy-
carbonylamino)-benzo[c]phenanthrenyl}carbamoyl-benzoic acid, (P)-
15. Under a hydrogen atmosphere, a mixture of (P)-14 (266 mg,
0.33 mmol) and palladium carbon (67 mg) in ethyl acetate (27 mL)
was vigorously stirred at room temperature for 3 h. Then, the
mixture was filtered, and filtrate was concentrated. Silica gel
chromatography (ethyl acetate/hexane¼1/2) gave (P)-15 (231 mg,
21
98%). Mp 142e143 ꢀC (hexane/ethyl acetate). [
a]
ꢂ239 (c 0.86,
D
CHCl3). MS (FAB, NBA) calcd for C44H50N2O7: 718.3615. Found:
718.3633. IR (KBr) 3253, 3066, 2954, 2925, 2854, 1728, 1703, 1660,
1599, 1523 cmꢂ1. Anal. (C44H50N2O7) Calcd: C, 73.51; H, 7.01; N,
3.90%. Found: C, 73.33; H, 7.03; N, 3.71%. 1H NMR (400 MHz, ace-
Found: C, 70.87; H, 7.29%. 1H NMR (400 MHz, CDCl3)
d 0.88 (3H, t,
J¼7 Hz), 1.27e1.48 (14H, m), 1.80 (2H, quint, J¼7 Hz), 4.38 (2H, t,
J¼7 Hz), 5.44 (2H, s), 7.35e7.49 (5H, m), 8.92 (1H, d, J¼2 Hz), 8.94
tone-d6)
d
0.84 (3H, t, J¼7 Hz), 1.25e1.52 (14H, m), 1.55 (9 H, s), 1.83
(2H, t, J¼2 Hz). 13C NMR (100 MHz, CDCl3)
d
14.1, 22.6, 25.9, 28.6,
(2H, quint, J¼7 Hz),1.94 (3H, s),1.95 (3H, s), 4.41 (2H, t, J¼7 Hz), 7.49
(2H, t, J¼6 Hz), 7.58e7.65 (2H, m), 8.23 (2H, d, J¼7 Hz), 8.26 (2H, d,
J¼8 Hz), 8.62 (1H, s), 8.84 (1H, s), 9.00 (1H, s), 9.02 (1H, s),10.26 (1H,
29.2, 29.3, 29.5 (two peaks), 31.9, 66.0, 67.5, 128.4, 128.5, 128.7, 130.2,
131.4, 131.8, 135.1, 135.2, 135.4, 135.5, 164.7, 164.8, 170.3.
s). 13C NMR (100 MHz, CDCl3)
d 14.1, 22.6, 23.4, 23.5, 25.9, 28.3, 28.6,
4.2.4. 3-Benzyloxycarbonyl-5-decyloxycarbonyl-1-benzoyl chloride,
13. Potassium salt was prepared by mixing 12 (132 mg, 0.30 mmol)
in THF/methanol (1/1, 3.0 mL) and 1.0 M potassium hydroxide in
methanol (0.27 mL) at 0 ꢀC. After being stirred for 5 min, the sol-
vents were removed, and the residue was dried at room tempera-
ture for 18 h in vacuo. Under an argon atmosphere, the potassium
salt was suspended in dichloromethane (3.0 mL), to which thionyl
29.3, 29.5 (two peaks), 31.8, 65.9, 67.3, 80.7, 118.2, 118.3, 118.7, 120.7,
121.6, 125.5, 125.6, 126.8, 126.9, 128.4, 128.5, 128.6, 130.7, 130.9,
131.3, 131.6, 131.7, 132.5, 132.7, 133.3, 135.4, 135.5, 136.6, 136.7, 153.9,
164.6, 164.9, 165.1.
4.2.7. (P)-5-(tert-Butoxycarbonylamino)-8-{3-(chlorocarbonyl)-5-
(decyloxycarbonyl)benzoylamino}-1,12-dimethylbenzo[c]

W. Ichinose et al. / Tetrahedron 67 (2011) 5477e5486
5485
phenanthrene, (P)-16. Potassium salt was prepared by mixing (P)-
15 (22 mg, 0.031 mmol) in THF/methanol (1/1, 0.30 mL) and 1.0 M
potassium hydroxide in methanol (0.028 mL) at 0 ꢀC. After being
stirred for 5 min, the solvents were removed, and the residue was
dried at room temperature for 18 h in vacuo. Under an argon at-
mosphere, to a suspension of the potassium salt in dichloro-
methane (0.31 mL) were added thionyl chloride (0.024 mL) and
DMF (3 drops). The mixture was stirred at ꢂ20 ꢀC for 1 h. Excess
thionyl chloride was removed in vacuo, and the residue was
azeotropically dried twice by added toluene (1.0 mL) and evapo-
rated in vacuo. The resulted acid chloride (P)-16 (18 mg, 92%)
122.0,123.8,124.6,124.8,126.6,128.3,128.4,130.8,131.4,131.8,132.1,
132.4, 134.3, 134.6, 135.6, 135.8, 165.2, 165.3.
4.2.10. Tetramer, (P)-3. Under an argon atmosphere, to a solution of
(P)-17 (23 mg, 0.026 mmol) in dichloromethane (1.0 mL) and pyr-
idine (0.16 mL) was added (P)-16 (50 mg, 0.068 mmol) in
dichloromethane (8.6 mL), and the mixture was stirred at room
temperature for 1 h. Then, 2 M hydrochloric acid was added, and
the organic materials were extracted with ethyl acetate twice. The
combined organic layers were washed with water, brine, and dried
over magnesium sulfate. Purification by silica gel chromatography
was purified by rapid silica gel chromatography.7 Mp 103e105 ꢀC
and GPC (THF) gave tetramer (P)-3 (28 mg, 48%). Mp 235 ꢀC
22
22
(hexane). [
a
]
ꢂ220 (c 0.65, CHCl3). MS (FAB, NBA) m/z calcd for
decomposed (hexane/THF). [
a
]
D
þ1345 (c 0.032, THF). MS
C44H49N2O635DCl: 736.3279. Found: 736.3317. IR (KBr) 3246, 2956,
(MALDI-TOF, 2-amino-5-nitropyridine) calcd for C147H154N8O16:
2925, 2854, 1766, 1730, 1691, 1655, 1525 cmꢂ1. 1H NMR (400 MHz,
2287.1474. Found: 2286.7969 ([MꢂH]ꢂ). IR (KBr) 3222, 2952, 2925,
2854, 1726, 1689, 1645, 1523 cmꢂ1. Anal. (C147H154N8O16) Calcd: C,
77.13; H, 6.79; N, 4.90%. Found: C, 76.73; H, 6.80; N, 4.70%. 1H NMR
CDCl3)
d
0.84 (3H, t, J¼7 Hz), 1.25e1.52 (14H, m), 1.55 (9 H, s), 1.83
(2H, quint, J¼7 Hz),1.94 (3H, s), 1.95 (3H, s), 4.41 (2H, t, J¼7 Hz), 7.49
(2H, t, J¼6 Hz), 7.58e7.65 (2H, m), 8.23 (2H, d, J¼7 Hz), 8.26 (2H, d,
J¼8 Hz), 8.62 (1H, s), 8.84 (1H, s), 9.00 (1H, s), 9.02 (1H, s),10.26 (1H,
(400 MHz, DMSO-d6)
d
0.78 (9H, t, J¼7 Hz), 1.19e1.45 (42H, m),
1.51 (18H, s), 1.79 (6H, quint, J¼7 Hz), 1.88 (12H, s), 1.94 (12H, s),
4.40 (6H, t, J¼6 Hz), 7.48 (4H, t, J¼7 Hz), 7.55 (4H, d, J¼7 Hz), 7.63
(4H, m), 7.69 (4H, t, J¼8 Hz), 7.99 (2H, s), 8.08 (2H, s), 8.14e8.22
(10H, m), 8.90 (6H, s), 9.16 (3H, s), 9.43 (2H, s), 10.97 (2H, s), 11.03
s). 13C NMR (100 MHz, CDCl3)
d 14.1, 22.6, 23.4, 23.5, 25.9, 28.3, 28.6,
29.3, 29.5 (two peaks), 31.8, 65.9, 67.3, 80.7, 118.2, 118.3, 118.7, 120.7,
121.6, 125.5, 125.6, 126.8, 126.9, 128.4, 128.5, 128.6, 130.7, 130.9,
131.3, 131.6, 131.7, 132.5, 132.7, 133.3, 135.4, 135.5, 136.6, 136.7, 153.9,
164.6, 164.9, 165.1.
(4H, s). 13C NMR (100 MHz, DMSO-d6)
d 14.1, 22.3, 23.2, 25.7, 28.4,
28.9, 29.1, 31.4, 65.6, 79.4, 119.0, 120.6, 121.1, 121.2, 122.4, 125.8,
126.2, 127.8, 128.2, 128.6, 128.8, 128.9, 130.9, 131.3, 131.4, 131.5,
131.6, 131.8, 131.9, 132.9, 133.1, 133.6, 135.7, 135.8, 136.0, 154.3,
165.1, 165.4.
4.2.8. Dimer (P)-2. Under an argon atmosphere, to a solution of (P)-
9 (7.9 mg, 0.020 mmol) in pyridine (0.06 mL) was added (P)-16
(18 mg, 0.025 mmol) in dichloromethane (4.9 mL), and the mixture
was stirred at room temperature for 1 h. Then, 2 M hydrochloric
acid was added, and the organic materials were extracted with
ethyl acetate twice. The combined organic layers were washed with
water, brine, and dried over magnesium sulfate. Purification by
Acknowledgements
Financial support and grant for research assistant from the
WPI-AIMR Fusion Research and the G-COE program from JSPS are
acknowledged. W.I. thanks the JSPS for a fellowship for young
Japanese scientists.
silica gel chromatography and GPC (THF) gave dimer (P)-2 (22.8 mg,
22
86%). Mp 244 ꢀC decomposed (hexane/THF). [
a
]
ꢂ363 (c 0.033,
D
THF). MS (MALDI-TOF, 2-amino-5-nitropyridine) calcd for
C69H74N4O8: 1086.5502. Found: 1086.2154. ([MꢂH]ꢂ). IR (KBr)
3261, 2956, 2925, 2854, 1724, 1689, 1647, 1523 cmꢂ1. Anal.
(C69H74N4O8) Calcd: C, 76.20; H, 6.86; N, 5.16%. Found: C, 76.16; H,
Supplementary data
6.77; N, 4.91%. 1H NMR (400 MHz, DMSO-d6)
d
0.80 (3H, t, J¼7 Hz),
These data include CD spectra of (P)-3. Supplementary data
associated with this article can be found in the online version, at
doi:10.1016/j.tet.2011.05.059. These data include MOL files and
InChIKeys of the most important compounds described in this
article.
1.20e1.46 (14H, m), 1.53 (18H, s), 1.79 (2H, quint, J¼7 Hz), 1.89 (6H,
s), 1.90 (6H, s), 4.41 (2H, t, J¼6 Hz), 7.50 (4H, t, J¼7 Hz), 7.64 (2H, t,
J¼8 Hz), 7.65 (2H, t, J¼8 Hz), 8.00 (2H, s), 8.09 (2H, s), 8.17 (4H, t,
J¼7 Hz), 8.89 (2H, s), 9.16 (1H, s), 9.44 (2H, s), 10.98 (2H, s). 13C NMR
(100 MHz, DMSO-d6)
d 14.1, 22.2, 23.2 (two peaks), 25.7, 28.4, 28.8,
28.9, 29.1 (two peaks), 31.4, 65.6, 79.4, 119.0, 120.6, 121.1, 122.4,
125.8,125.9, 127.8,128.2,128.6,128.7,130.9, 131.3,131.4,131.5,131.8,
131.9, 132.8, 133.6, 135.8, 154.3, 165.1, 165.4.
References and notes
1. (a) Berl, V.; Huc, I.; Khoury, R. G.; Krische, M. J.; Lehn, J.-M. Nature 2000, 407,
720e723; (b) Berl, V.; Huc, I.; Khoury, R. G.; Lehn, J.-M. Chem.dEur. J. 2001, 7,
2810e2820; (c) Jiang, H.; Maurizot, V.; Huc, I. Tetrahedron 2004, 60,
10029e10038; (d) Dolain, C.; Zhan, C.; Legar, J.-M.; Daniels, L.; Huc, I. J. Am.
Chem. Soc. 2005, 127, 2400e2401; (e) Zhan, C.; Legar, J.-M.; Huc, I. Angew. Chem.,
Int. Ed. 2006, 45, 4625e4628; (f) Haldar, D.; Jiang, H.; Legar, J.-M.; Huc, I. Angew.
Chem., Int. Ed. 2006, 45, 5483e5486; (g) Haldar, D.; Jiang, H.; Legar, J.-M.; Huc, I.
Tetrahedron 2007, 63, 6322e6330; (h) Berni, E.; Kauffmann, B.; Bao, C.; Lefeuvre,
J.; Bassani, D. M.; Huc, I. Chem.dEur. J. 2007, 13, 8463e8469; (i) Sanchez-Garcia,
D.; Kauffmann, B.; Kawanami, T.; Ihara, H.; Takafuji, M.; Delville, M.-H.; Huc, I. J.
Am. Chem. Soc. 2009, 131, 8642e8648; (j) Baptiste, B.; Zhu, J.; Haldar, D.;
Kauffmann, B.; Legar, J.-M.; Huc, I. Chem.dAsian J. 2010, 13, 1364e1375.
2. Yan, Y.; Oin, B.; Shu, Y.; Chen, X.; Yip, Y. K.; Zhang, D.; Su, H.; Zeng, H. Org. Lett.
2009, 11, 1201e1204.
3. Bisson, A. P.; Carver, F. J.; Eggleston, D. S.; Haltiwanger, R. C.; Hunter, C. A.;
Livingstone, D. L.; McCabe, J. F.; Rotger, C.; Rowan, A. E. J. Am. Chem. Soc. 2000,
122, 8856e8868.
4. Okamoto, I.; Nabeta, M.; Hayakawa, Y.; Morita, N.; Takeya, T.; Masu, H.; Azu-
maya, I.; Tamura, O. J. Am. Chem. Soc. 2007, 129, 1892e1893.
5. Yuan, L.; Zeng, H.; Yamato, K.; Sanford, A. R.; Feng, W.; Atreya, H. S.; Sukumaran,
D. K.; Szyperski, T.; Gong, B. J. Am. Chem. Soc. 2004, 126, 16528e16537.
6. Hu, H.-Y.; Xue, W.; Hu, Z.-Q.; Xiang, J.-F.; Chen, C.-F.; He, S.-G. J. Org. Chem. 2009,
74, 4949e4957.
7. Amemiya, R.; Ichinose, W.; Yamaguchi, M. Bull. Chem. Soc. Jpn. 2010, 83,
809e815.
4.2.9. Diamine (P)-17. Under an argon atmosphere, to a solution of
(P)-2 (58 mg, 0.053 mmol) in dichloromethane (2.1 mL) was added
trifluoroacetic acid (0.40 mL) at 0 ꢀC. The mixture was stirred vig-
orously at room temperature for 1 h. The reaction was quenched by
adding saturated aqueous sodium bicarbonate at 0 ꢀC, and the or-
ganic materials were extracted with ethyl acetate twice. The com-
bined organic layers were washed with water and brine, and dried
over magnesium sulfate. The solvents were removed in vacuo, and
purification by silica gel chromatography and GPC (THF) gave di-
amine (P)-17 (43 mg, 90%). Mp 180e185 ꢀC (hexane/ethyl acetate).
22
[
a]
ꢂ691 (c 0.69, DMSO). MS (FAB, NBA) calcd for C59H58N4O4:
D
886.4455. Found: 886.4448. IR (KBr) 3354, 3248, 2952, 2924, 2852,
1718, 1670, 1520 cmꢂ1. 1H NMR (400 MHz, DMSO-d6)
d
0.80 (3H, t,
J¼7 Hz),1.20e1.47 (14H, m),1.79 (2H, quint, J¼7 Hz),1.85 (6H, s),1.89
(6H, s), 4.40 (2H, t, J¼6 Hz), 6.10 (4H, s), 7.38e7.49 (6H, m), 7.55 (2H,
t, J¼8 Hz), 7.82 (2H, s), 8.04 (2H, d, J¼8 Hz), 8.17 (2H, d, J¼8 Hz), 8.87
(2H, s), 9.13 (1H, s), 10.83 (2H, s). 13C NMR (100 MHz, DMSO-d6)
d
14.1, 22.3, 23.4, 25.7, 28.4, 28.9, 29.1, 31.5, 65.6, 115.7, 120.0, 120.9,
8. Okubo, H.; Nakano, D.; Anzai, S.; Yamaguchi, M. J. Org. Chem. 2001, 66, 557e563.

5486
W. Ichinose et al. / Tetrahedron 67 (2011) 5477e5486
9. (a) Zeng, H.; Miller, R. S.; Flowers, R. A., II; Gong, B. J. Am. Chem. Soc. 2000, 122,
2635e2644; (b) Zeng, H.; Ickes, H.; Flowers, R. A., II; Gong, B. J. Org. Chem. 2001,
66, 3574e3583.
2008, 3, 244e260; (d) Amemiya, R.; Saito, N.; Yamaguchi, M. J. Org. Chem. 2008,
73, 7137e7144.
12. (a) McLachlan, R. D.; Nyquist, R. A. Spectrochim. Acta 1964, 20,1397e1406; (b) Torii,
H.;Tatsumi, T.;Kanazawa,T.;Tasumi, M.J.Phys. Chem. B1998,102, 309e314;(c)Lee,
M.-E.; Lee, S. Y.; Joo, S.-W.; Cho, K.-H. J. Phys. Chem. B 2009, 113, 6894e6897.
13. Ishida, H.; Qi, Z.; Sokabe, M.; Donowaki, K.; Inoue, Y. J. Org. Chem. 2001, 66,
2978e2989.
10. Bitta, J.; Kubik, S. Org. Lett. 2001, 3, 2637e2640.
11. (a) Sugiura, H.; Nigorikawa, Y.; Saiki, Y.; Nakamura, K.; Yamaguchi, M. J. Am.
Chem. Soc. 2004, 126, 14858e14864; (b) Sugiura, H.; Yamaguchi, M. Chem. Lett.
2007, 36, 58e59; (c) Sugiura, H.; Amemiya, R.; Yamaguchi, M. Chem.dAsian. J.