Isolation of Epimers in the Synthesis of Vinylcyclopropane Bearing Two Alanine Moieties and Their Radical Ring-Opening Polymerization

Article abstract of DOI:10.1021/acs.macromol.6b02778

By condensing 1,1-dicarboxy-2-vinylcyclopropane with l-alanine methyl ester, a new chiral vinylcyclopropane derivative bearing two amide moieties 1 was synthesized. The vinylcyclopropane thus prepared was separated into two epimers, namely, RSS-1 and SSS-1. Both the epimers and an epimeric mixture underwent radical ring-opening polymerization (RROP), where the number-average molecular weights (M_ns) of the polymers depended on the configuration of 1; i.e., the RROP of SSS-1 gave the corresponding polymer, of which M_n was higher than the polymer obtained by the RROP of RSS-1. This difference in polymerization behaviors was correlated successfully with the difference in manners of intermolecular and intramolecular hydrogen bonds between the two epimers, which were clarified by the polymerization of SSS-1 was assisted by intermolecular hydrogen bonds. Besides the RROP in solution, the RROP of SSS-1 in its solid state was investigated to find that it afforded the corresponding polymer highly efficiently.

Full text of DOI:10.1021/acs.macromol.6b02778

Article
pubs.acs.org/Macromolecules
Isolation of Epimers in the Synthesis of Vinylcyclopropane Bearing
Two Alanine Moieties and Their Radical Ring-Opening
Polymerization
Naoya Takahashi,† Atsushi Sudo,‡ and Takeshi Endo*,†
†Molecular Engineering Institute, Kindai University, 11-6 Kayanomori, Iizuka, Fukuoka 820-8555, Japan
‡Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University, Kowakae 3-4-1, Higashi Osaka, Osaka
577-8502, Japan
S
* Supporting Information
ABSTRACT: By condensing 1,1-dicarboxy-2-vinylcyclopro-
pane with L-alanine methyl ester, a new chiral vinyl-
cyclopropane derivative bearing two amide moieties 1 was
synthesized. The vinylcyclopropane thus prepared was
separated into two epimers, namely, RSS-1 and SSS-1. Both
the epimers and an epimeric mixture underwent radical ring-
opening polymerization (RROP), where the number-average
molecular weights (Mns) of the polymers depended on the configuration of 1; i.e., the RROP of SSS-1 gave the corresponding
polymer, of which Mn was higher than the polymer obtained by the RROP of RSS-1. This difference in polymerization behaviors
was correlated successfully with the difference in manners of intermolecular and intramolecular hydrogen bonds between the two
epimers, which were clarified by the polymerization of SSS-1 was assisted by intermolecular hydrogen bonds. Besides the RROP
in solution, the RROP of SSS-1 in its solid state was investigated to find that it afforded the corresponding polymer highly
efficiently.
intrinsically high distortion energy that drives its ring-opening
reaction. (3) The radical species formed as a result of the ring-
opening reaction can be stabilized by the neighboring
functional groups such as ester, halogen, and amide groups.
Recently, Contreras et al. have reported a photoinduced RROP
of 1,1-disubstituted VCP derivatives bearing amide moieties.9,10
Therein, they have postulated the role of the amide bond to
accelerate the polymerization by contracting the monomer
molecules by hydrogen bonding.
On the other hand, considerable interests have been focused
on development of monomers using naturally occurring amino
acids as starting materaials11−18 because their polymerizations
give functional materials with chirality and stimulus-responsive
properties that can be applied to drug delivery and biocatalysts
systems. VCP derivatives derived from amino acids are also
attractive monomers because they can be used for synthesizing
highly functionalized polymers with optically active nature. So
far, such VCP derivatives have been synthesized and used as a
key building blocks for synthesizing bioactive molecules.19−22
Herein, we report new 1,1-disubstituted VCP 1 bearing two
L-alanine-derived moieties (Figure 1). Its two epimers, RSS-1
and SSS-1, were prepared, and their structures were clarified by
NMR spectroscopy and X-ray crystallography. Their RROP
behaviors were studied in detail to find their interesting
1. INTRODUCTION
Vinylcyclopropane (VCP) derivatives are important molecules
in various fields such as pharmaceutical, agrochemicals, and
material science because of the high reactivity of the
cyclopropane moiety that allows efficient uses of VCP
derivatives as reactive precursors for functional compounds.
The 1,1-disubstituted VCP derivatives undergo radical ring-
opening polymerization (RROP) mainly via 1,5-ring-opened
reaction along with a minor pathway forming cyclobutane
moiety (Scheme 1).1−8 The high polymerization ability of VCP
derivative arises from the following factors: (1) The vinyl group
serves as a radical acceptor. (2) The cyclopropane ring has
Scheme 1. RROP System of VCP Derivatives
Received: February 11, 2017
Revised: May 31, 2017
© XXXX American Chemical Society
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Figure 1. Molecular structures of RSS-1 and SSS-1.
dependence on the stereochemistry of the epimers. The
motivation of this work was to clarify the role of hydrogen
bonds in the radical RROP of VCPs. What we expected was
that the difference in configuration of the VCP monomers
would arise the difference in the manner of hydrogen bonds
(intra- or intermolecular, etc.) and thus give an impact on the
polymerization behaviors.
Figure 2. Thermal ellipsoidal model of RSS-1. The ellipsoids are at
50% probability. An intramolecular hydrogen bond is depicted as a
dashed line.
Table 1. Lengths of the C−C Bonds Composing the
2. RESULTS AND DISCUSSION
2.1. Synthesis and Isolation of Epimers of VCP
Derivative 1. Scheme 2 shows the route for the synthesis of
Cyclopropane Moiety of RSS-1 in Its Crystalline Structure
C−C bonds
C1−C2
C12−C13
C13−C1
length (Å)
1.54
1.48
1.51
Scheme 2. Synthesis of VCP Derivative 1
respectively. The length of C1−C12 was longer than the others,
suggesting that the C1−C12 bond was potentially more
scissible during the RROP of RSS-1.1−8 The X-ray analysis
revealed the presence of an intramolecular hydrogen bond
between the hydrogen atom on the nitrogen N1 and the
oxygen O5 in one of the ester carbonyl groups (Figure 2).
The alignment of the RSS-1 molecules in the crystalline state
is shown in Figure 3. It clarifies that two RSS-1 molecules are
VCP derivative 1. Diethyl malonate was converted to 1,1-
diethoxycarbonyl-2-vinylcyclopropane (DECVCP) by cyclo-
propanating with 1,4-dibromobutene in the presence of NaH in
dry THF. In the next step, the ester moieties of DECVCP were
hydrolyzed under basic conditions to obtain 1,1-dicarboxyl-2-
vinylcyclopropane (DCAVCP). In the final step, DCAVCP was
condensed with L-alanine methyl ester to afford 1 as a 1:1
mixture of the two epimers, RSS-1 and SSS-1. Both the isomers
were isolated easily by silica-gel column chromatography.
2.2. X-ray Crystallography of RSS-1 and SSS-1. Guha et
al. have reported a crystal structure of a cyclopropane derivative
connected with two valine moieties via amide bonds.23−25 In
the crystalline state, the cyclopropane molecules aligned in a
helix structure regulated by intermolecular and intermolecular
hydrogen bonds using the two amide groups.
A single crystal of RSS-1 was prepared from its solution in
chloroform/hexane (1/15) and analyzed by single crystal X-ray
structure analysis. The crystal data are summarized in Table S1
of the Supporting Information. The crystal structure in an
elliposidal model and the lengths of the C−C bonds composing
the cyclopropane ring are shown in Figure 2 and Table 1,
Figure 3. Hydrogen bonds between two molecules of RSS-1.
bridged by one water molecule via hydrogen bonds: (1) the
hydrogen bond between water OH (O7−H1) and amidecar-
bonyl oxygen (O1), (2) that between water OH (O7−H2) and
ester carbonyl oxygen (O2), and (3) that between the
hydrogen atom on the nitrogen (N2) and oxygen of water
(O7). The details of the intra- and intermolecular hydrogen
bonds are shown in Table 2.
Next, the crystal structure of SSS-1 was analyzed. A needle-
like crystal of SSS-1 was prepared from its solution in ethyl
acetate/chloroform/hexane (1/5/32), and its single crystal
structure X-ray analysis was performed. The crystal data are
shown in Table S1. The crystal structure in an ellipsoidal model
and the lengths of the C−C bonds composing the cyclo-
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Table 2. Geometry of the Hydrogen Bonds in the Crystalline
State of RSS-1
Table 3. Lengths of the C−C Bonds Composing the
Cyclopropane Moiety of SSS-1 in Its Crystalline Structure
D−H
H···A
(Å)
D···A
(Å)
D−H···A
C−C bonds
length (Å)
C1−C12
1.51
C12−C13
1.50
C13−C1
1.54
D−H···A
(Å)
(deg)
mode
O7−H1···O1
O7−H2···O2
N2−H···O7
N1−H···O5
0.88
0.86
0.88
0.88
1.89
1.95
1.95
2.25
2.76
2.93
2.81
3.11
170
178
167
168
intermolecular
intermolecular
intermolecular
intramolecular
propane ring are depicted in Figure 4 and Table 3, respectively.
The length of C13−C1 was longer than the others, suggesting
that the C13−C1 bond is potentially more scissible during
RROP of SSS-1.
In the crystal structure of SSS-1, there was an intramolecular
hydrogen bond in a different manner to that in the crystal
structure of RSS-1. The intermolecular hydrogen bond
connected one amide moiety with the other amide moiety,
not with an ester moiety.
The alignment of the SSS-1 molecules in the crystalline state
is shown in Figure 5. The molecules of SSS-1 are aligned in a
linear supramolecular structure by intermolecular hydrogen
bonds between the amide carbonyl oxygen O1 and the
hydrogen atom on the nitrogen N1. The amide caronyl oxygen
O1 plays another important role to construct the crystal
structures; i.e., it formed an intramolecular hydrogen bond with
the hydrogen atom on the nitrogen N2. The details of the intra-
and intermolecular hydrogen bonds are shown in Table 4. On
the other hand, another amide carbonyl oxygen O4 was not
involved in the hydrogen bond network.
Figure 5. Alignment of SSS-1 molecules in the crystalline state.
Table 4. Geometry of Hydrogen Bonds of RSS-1 in the
Crystalline State
D−H
H···A
(Å)
D···A
(Å)
D−H···A
D−H···A
(Å)
(deg)
mode
N1−H···O1
N2−H···O1
0.88
0.88
1.99
2.33
2.77
2.93
147
125
intermolecular
intramolecular
epimers are depicted as the arrows. The structures of the
epimers are drawn with taking account of the intramolecular
hydrogen bonds clarified by the X-ray crystallographic data.
In the NOESY spectrum of RSS-1, there was NOE between
Hc and Hf, while there was no NOE between Hc and He, to
confirm the assignment of their 1H NMR signals. The NOESY
spectrum also confirmed the assignments for the amide
protons: Between He on the cyclopropane ring and Hg on
one of the amide moieties, of which close location with each
other can be expected from the configuration of RSS-1, there
was NOE. Similarly, between Hf and amide proton Hk, there
was NOE. In addition, NOE was observed between the two
amide protons Hg and Hk to confirm they are located closely
with each other. The close location between the two amide
protons predicted by the NOEs is in good agreement with the
2.3. NMR Study of 1. The isolated epimers, RSS-1 and SSS-
1
1, were analyzed by NMR. The H and 13C NMR spectra are
1
shown Figures 6 and 7, respectively. When the two H NMR
spectra of the two epimers were compared, significant
differences in chemical shift were observed for the signals
attributable to the amide protons and the protons on the
cyclopropane ring. Similarly, when the two 13C NMR spectra
were compared, significant differences in chemical shift were
observed for the signals attributable to the amide carbonyl
carbons and the carbons composing the cyclopropane moiety.
To get an insight into the conformations of the epimers in
solution state, their NOESY spectra were measured. The
resulting data are shown in the Supporting Information. In
Figure 8, the observed NOEs around VCP moieties in both
Figure 4. Thermal ellipsoidal model of SSS-1. The ellipsoids are at 50% probability. An intramolecular hydrogen bond is depicted as a dashed line.
C
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bridged by an intramolecular hydrogen bond to make the
distance between Hk and Hg short as 2.74 Å.
The NOESY spectrum of SSS-1 confirmed the assignments
1
of the relevant H NMR signals to the corresponding protons,
He′ and Hf′ on the cyclopropane ring and the amide protons
Hg′ and Hk′: There was NOE between Hc′ and He′, while
there was not NOE between Hc′ and Hf′. NOE between He′
and Hg′ and that between Hf′ and Hk′ were observed. The
remarkable difference of the NOESY spectrum of SSS-1 from
that of RSS-1 was that there was no NOE between the two
amide protons Hg′ and Hk′. The lack of NOE was in good
agreement with the distance between them (3.69 Å) in the
crystalline state of SSS-1 as a result of the intramolecular
hydrogen bond between the two amide moieties forming 6-
membered ring including the amide proton Hk′.
2.4. RROP of 1. The polymerizations of both isolated
epimers (RSS-1 and SSS-1) and a 1:1 mixture of RSS-1 and
SSS-1 were performed using azobisisobutyronitrile (AIBN) as
an initiator (Scheme 3). As a solvent, dimethylformaldehyde
Scheme 3. RROP of 1
Figure 6. 1H NMR spectra of RSS-1 (upper) and SSS-1 (lower)
measured in CDCl3.
(DMF) or chloroform was chosen. The results are summarized
in Table 5. In all cases using 3 mol % of AIBN, 1 was consumed
1
completely. The H and 13C NMR spectra of the resulting
polymers revealed that they did not contain any cyclobutane
moiety, and the configuration of the vinylene in the main chains
was trans irrelevantly to the stereochemistry of 1. The chirality
of the cyclopropane moiety was lost by the ring-opening
1
reaction. As typical examples, H and 13C NMR spectra of
poly1 obtained by RROP of the 1:1 mixture of RSS-1 and SSS-1
performed in DMF (Table 5, entry 1) are shown in Figure 9.
To clarify the difference in reactivity between the two
epimeric monomers, their polymerizations were performed
independently using 0.3 mol % AIBN. As a result, SSS-1 was
consumed completely (entry 8) while the conversion of RSS-1
was only 38% (entry 5).
Figure 7. 13C NMR spectra of RSS-1 (upper) and SSS-1 (lower)
The data shown in Table 5 clarified two tendencies: (1) The
polymerizations in chloroform yielded the corresponding
polymers having higher molecular weights within shorter
polymerization time than those in DMF. (2) When 3 mol %
AIBN was used, the polymerizations of SSS-1 yielded the
corresponding polymers having higher molecular weights than
those of its epimer RSS-1 and those of the 1:1 mixture of the
epimers. (3) When 0.3 mol % AIBN was used, SSS-1
underwent the polymerization more efficiently than RSS-1
and the 1:1 mixture of the epimers.
measured in CDCl3.
The higher molecular weights of the polymers synthesized in
chloroform than those of the polymers synthesized in DMF
implied that intermolecular hydrogen bonds between the amide
moieties located at the propagating end and monomer 1
assisted the more efficient propagation reaction in chloroform
than in DMF where the intermolecular hydrogen bonding are
Figure 8. Selected NOEs around vinylcyclopropane moieties.
conformation clarified by the X-ray crystallography, in which
the amide proton Hk and the ester carbonyl oxygen OA were
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Table 5. RROP of 1
a
b
c
c
entry
monomer
solvent
AIBN (mol %)
time (h)
conv (%)
yield (%)
Mn (×103)
Mw/Mn
1
2
3
4
5
6
7
8
9
1 (mix)
1 (mix)
1 (mix)
RSS-1
RSS-1
RSS-1
SSS-1
DMF
DMF
CHCl3
DMF
DMF
CHCl3
DMF
DMF
CHCl3
3
20
20
4
>99
58
66
43
42
84
25
59
87
87
91
22
46
2.4
2.5
3.6
3.4
1.8
2.7
2.2
3.0
2.6
0.3
3
>99
>99
38
76
3
20
20
4
54
0.3
3
263
64
>99
>99
>99
>99
3
20
20
4
72
SSS-1
0.3
152
SSS-1
3
100
a
b
c
Determined by 1H NMR. Ether-insoluble parts. Estimated by SEC (calibrated with polystyrene standards, eluted with DMF containing 10 mM
LiBr).
1
Figure 9. H and 13C NMR spectra of poly1 synthesized from epimeric mixture of 1 in DMF by 3 mol % AIBN in CDCl3, respectively.
inhibited by the higher polarity of DMF. As clarified by the X-
ray crystallography, the molecules of SSS-1 tend to interact with
each other by hydrogen bonds more strongly than the
molecules of RSS-1. This intrinsic nature of SSS-1 would be a
reason for its higher polymerization ability than that of its
epimer, RSS-1. A similar RROP of VCP amide monomers
assisted by intermolecular hydrogen bonds has been reported
by Contreras et al.9,10
heated at 60 °C for 20 h. As a result, the solid-phase RROP of
SSS-1 using AIBN as an initiator proceeded efficiently, leading
to the quantitative consumption of SSS-1 (Table 6, entry 1).
Table 6. RROP of SSS-1 in the Crystalline State
a
b
c
c
entry
AIBN (%)
10
conv (%)
>99
yield (%)
51
Mn (×103)
Mw/Mn
1
2
33
8.3
0
0
2.5. Polymerization of SSS-1 in Its Solid State. The last
topic of this paper is polymerization of SSS-1 in its solid state.
So far, polymerizations of several monomers in their solid states
have been reported.26−28 Such solid-phase polymerizations can
be achieved by appropriate alignments of monomers in crystals.
Kanazawa et al. have reported that the polymerization of amino
acid NCAs proceeded in their solid state, and these solid-phase
polymerizations were faster than the conventional solution-
phase polymerizations of the same monomers.26 As shown in
Figure 5, in the crystal structure of SSS-1, the vinylcyclopropane
moieties were aligned in a linear supramolecular structure,
leading to our postulation that SSS-1 would undergo RROP in
its solid state.
a
b
c
1
Determined by H NMR. Ether-insoluble parts. Estimated by SEC
(calibrated with polystyrene standards, eluted with DMF containing 10
mM LiBr).
AIBN was indispensable to the polymerization (entry 2).
Throughout the polymerization, the crystals did not dissolve in
hexane or melt, implying that AIBN penetrated into the crystals
through their defects and then initiated the polymerization.
Figure S7 in the Supporting Information shows the H NMR
spectrum of the resulting polymer, which was mostly identical
1
with that of poly 1 synthesized in DMF.
Scheme 5 shows hypothetical polymerization mechanism of
the solid-phase polymerization of SSS-1. VCP moieties were
located near to next molecules by intermolecular hydrogen
bonds with high order, which supported efficient polymer-
ization in crystal state of SSS-1.
To perform the polymerization, hexane was used as a
medium because it does not dissolve 1 at all to allow the
crystals of SSS-1 to be dispersed in it. To the dispersion, AIBN
was added as a radical initiator, and the resulting mixture was
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of the epimers. In addition, chloroform was superior than N,N-
dimethylformamide (DMF) as a solvent to afford polymers
having higher molecular weights. These results suggested that
the polymerization of SSS-1 was assisted by intermolecular
hydrogen bonds. SSS-1 underwent RROP in its solid state,
where the alignment of the molecules regulated by the
hydrogen bonds suited for the successful RROP.
Scheme 4. RROP of SSS-1 in the Crystalline State
4. EXPERIMENTAL SECTION
1
4.1. Instruments. H and 13C NMR spectra were recorded with a
JEOL ECS-400 (400 MHz) spectrometer, and chemical shifts were
recorded in ppm using tetramethylsilane or solvent peaks as standards.
IR spectra were recorded on a Thermo Scientific Nicolet iS10
spectrometer equipped with a Smart iTR sampling accessory using
attenuated total reflection (ATR) method. For the estimation of
number-average molecular weight (Mn) and weight-average molecular
weight (Mw) of the synthesized polymers, SEC was performed on a
TOSOH HLC-8220 system equipped with three consecutive
polystyrene gel columns [TSK-gels (bead size, exclusion limited
molecular weight); super-AW4000 (6 μm, >4 × 105), super-AW3000
(4 μm, >6 × 104), and super-AW2500 (4 μm, >2 × 103)] and
refractive index and ultraviolet detectors at 40 °C. The system was
operated using 10 mM LiBr in DMF as the eluent at a flow rate of 0.5
mL/min. Polystyrene standards were used for calibration. Melting
point was measured on a Bibby Stuart Scientific melting point
apparatus SMP3. High-resolution mass spectra (HRMS) were
obtained on a JEOL JMN-700 spectrometer using electron impact
(EI) ionization mode. X-ray crystal structure data were collected using
a Bruker SMART APEX II diffractometer with Cu Kα radiation.
4.2. Chemicals. L-Alanine, sodium hydroxide, NaH (60%
dispersion in mineral oil), diethylmalonate, thionyl chloride, HOBt
monohydrate, and all solvents were purchased from Wako Pure
Chemical Industry (Osaka, Japan). EDC·HCl, N,N-diisopropyl-
ethylamine, 1,4-dibromo-2-butene, and sodium hydrate were pur-
chased from Tokyo Chemical Industry (Tokyo Japan). Chloroform,
THF, and DMF were distilled prior to use. Methanol and ether were
dried over molecular sieves 3A. Other solvents and reagents were used
as received. L-Alanine methyl ester hydrochloride was prepared from L-
alanine by a standard procedure using dry methanol and thionyl
chloride. 1,1-Diethoxycarbonyl-2-vinylcyclopropane (DECVCP) and
1,1-dicarboxyl-2-vinylcyclopropane (DCAVCP) were synthesized by
the previously reported methods.1,6,7,25
Scheme 5. Plausible Mechanism of RROP of SSS-1 in the
Crystalline State
4.3. Synthesis of 1,1-Bis(N-α-amido-L-alanine methyl ester)-
2-vinylcyclopropane (1). To a solution of DCAVCP (3.43, 21.9
mmol) in chloroform (25 mL), a solution of L-alanine methyl ester
hydrochloride (6.79 g, 48.7 mmol) and DIPEA (8.4 mL, 48.2 mmol)
in chloroform (25 mL) was added. To the resulting mixture, EDC·HCl
(9.55 g, 49.8 mmol) and HOBt monohydrate (6.42 g, 47.5 mmol)
were added at 0 °C. The mixture was stirred at room temperature
under nitrogen. After 24 h, 2% hydrochloric acid was added to the
solution, and the resulting precipitates were removed by filtration. The
filtrate was diluted with chloroform (300 mL), washed by saturated
NaHCO3(aq) and brine, dried over Na2SO4, filtered, and concentrated
under reduced pressure. The resulting residue was purified by flash
silica-gel column chromatography (eluent: ethyl acetate/hexane = 1/
5) to obtain 1,1-bis(N-α-amido-L-alanine methyl ester)-2-(R)-vinyl-
cyclopropane (RSS-1) (1.35 g; 4.1 mmol, 19%) and 1,1-bis(N-α-
amido-L-alanine methyl ester)-2-(S)-vinylcyclopropane (SSS-1) (1.48
g; 4.5 mmol, 20%).
3. CONCLUSION
A 1,1-disubstituted vinylcyclopropane derivative with two L-
alanine methyl ester moieties (1) was synthesized as a mixture
of two epimers. The epimers, RSS-1 and SSS-1, were separated
by silica-gel column chromatography, and their structures were
studied by X-ray crystallography. In a crystal of RSS-1, the
molecules were connected by intermolecular hydrogen bonds
to form a network, in which water molecules were participated.
However, those hydrogen bonds did not contribute to shorten
the distance between the vinylcyclopropane moieties of the
neighboring two RSS-1 molecules. On the other hand, in a
crystal of SSS-1, the intermolecular hydrogen bonds make the
molecules to be aligned in a linear supramolecular, in which the
vinylcyclopropane moieties of the neighboring two SSS-1
molecules were located much closer.
Both the epimers and an epimeric mixture underwent radical
ring-opening polymerization to afford the corresponding
polymers, which were identical to each other regardless of
the configurations of 1. The number-average molecular weights
of the polymers obtained by the polymerizations of SSS-1 were
higher than those of the polymers obtained by the polymer-
izations of RSS-1. It was also clarified that SSS-1 underwent the
polymerization more efficiently than RSS-1 and the 1:1 mixture
RSS-1: Obtained as pale yellow oil. 1H NMR (CDCl3): δ 7.88 (1H,
d, J = 7.2 Hz, NH), 7.10 (1H, d, J = 7.2 Hz, NH), 5.45−5.34 (1H, m,
CHC), 5.29 (1H, dd, J = 2.0, 17.2 Hz, CCH (trans)), 5.11 (1H,
dd, J = 2.0, 10 Hz, CCH (cis)), 4.63−4.55 (2H, m, N−CH × 2),
3.77, 3.76 (3H + 3H, s, OCH3 × 2), 2.62−2.56 (1H, m, CC−CH),
1.65 (1H, dd, J = 4.8, 7.6 Hz, CH trans to vinyl), 1.55 (1H, dd, J = 4.8,
8.4 Hz, CH (cis to vinyl)), 1.47, 1.46 (3H + 3H, d, J = 7.2 Hz, CH3 ×
2). 13C NMR (CDCl3): δ 174.71 (CO ester), 174.52 (CO ester),
169.60 (CO amide), 167.95 (CO amide), 134.00 (CHCH2),
118.09 (CHCH2), 52.74 (OCH3), 52.54 (OCH3), 48.95 (NCH),
F
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48.90 (NCH), 37.39 (CO−C−CO), 31.32 (CC−C), 19.61 (CH2 in
cyclopropane), 16.90 (CCH3), 16.81 (CCH3). HRMS (EI): found m/
z 326.1478, calcd for C15H22N2O6; M+: 326.1478.
Notes
The authors declare no competing financial interest.
Single crystals of RSS-1 for its X-ray crystallography was prepared as
follows: RSS-1 (40 mg) was dissolved in a mixture of chloroform (2.5
mL). To the resulting solution, hexane (160 mL) was added slowly,
and the resulting solution was left to stand for 16 h at room
temperature to obtain columnar single crystals.
ACKNOWLEDGMENTS
■
We thank Dr. Michio Yoshizawa and Dr. Yoshihisa Sei of
Tokyo Institute of Technology and Dr. Hyuma Masu of Chiba
Univ. for their experimental assistance of crystal analyses. Also,
this work was financially supported by JSR Corporation.
1
SSS-1. Obtained as a colorless crystal; mp = 99−100 °C. H NMR
(CDCl3): δ 7.61 (1H, d, J = 6.8 Hz, NH), 7.05 (1H, d, J = 6.8 Hz,
NH), 5.61−5.52 (1H, m, CHC), 5.30 (1H, dd, J = 2.0, 16.8 Hz,
CCH (trans)), 5.16 (1H, d, J = , 10.8 Hz, CCH (cis)), 4.55−4.53
(2H, m, N−CH × 2), 3.77, 3.74 (3H + 3H, s, OCH3 × 2), 2.33−2.27
(1H, m, Hz, CC−CH), 1.86 (1H, dd, J = 5.2, 8.8 Hz, CH trans to
vinyl), 1.49 (1H, dd, J = 5.2, 6.8 Hz, CH (cis to vinyl)), 1.44, 1.43 (3H
+ 3H, d, J = 7.2 Hz, CH3 × 2). 13C NMR (CDCl3): δ: 173.33 (CO
ester), 173.17 (CO ester), 168.59 (CO amide), 167.97 (CO
amide), 133.73 (CHCH2), 118.35 (CHCH2), 52.60 (OCH3),
52.42 (OCH3), 48.64 (NCH × 2), 36.31 (CO−C−CO), 32.18 (C
C−C), 18.36 (CH2 in cyclopropane), 17.85 (CCH3), 17.71 (CCH3).
HRMS (EI): found m/z 326.1478, calcd for C15H22N2O6; M+:
326.1477.
REFERENCES
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(118.5 mg, 66%) as white powder: H NMR (CDCl3): δ: 7.45 (2H,
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m, N−CH × 2), 3.73 (6H, brs, OCH3 × 2), 2.52 (4H, brs, CH2−
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4.5. RROP of SSS-1 in Its Crystalline State. To crystalline SSS-1
(32.1 mg, 98.4 mmol), AIBN (1.6 mg, 9.8 mmol, 10 mol % to 1), and
hexane (1.6 mL) were added. The mixture was degassed by three
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ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.macro-
mol.6b02778.
(14) Yamada, S.; Koga, K.; Sudo, A.; Goto, M.; Endo, T. Phosgene-
Free Synthesis of Polypeptides: Useful Synthesis for Hydrophobic
Polypeptides through Polycondensation of Activated Urethane
Derivatives of α-Amino Acids. J. Polym. Sci., Part A: Polym. Chem.
2013, 51, 3726−3731.
Crystal data of RSS-1 and SSS-1 and NMR spectra of
DECVCP, DCAVCP, RSS-1, and SSS-1 (PDF)
(15) Weller, D.; Medina-Oliva, A.; Claus, H.; Gietzen, S.; Mohr, K.;
Reuter, A.; Schaffel, D.; Schottler, S.; Koynov, K.; Bros, M.; Grabbe, S.;
̈
̈
AUTHOR INFORMATION
■
Fischer, K.; Schmidt, M. Solution Properties and Potential Biological
Applications of Zwitterionic Poly(ε- N -Methacryloyl- L -Lysine).
Macromolecules 2013, 46, 8519−8527.
(16) Banerjee, S.; Maji, T.; Paira, T. K.; Mandal, T. K. Amino-Acid-
Based Zwitterionic Polymer and Its Cu(II)-Induced Aggregation into
Nanostructures: A Template for CuS and CuO Nanoparticles.
Macromol. Rapid Commun. 2013, 34, 1480−1486.
Corresponding Author
*(T.E.) E-mail tendo@moleng.fuk.kindai.ac.jp; Fax +81-6-
6723-2721.
ORCID
Takeshi Endo: 0000-0002-0659-217X
G
DOI: 10.1021/acs.macromol.6b02778
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