8360
A. Miyawaki et al. / Tetrahedron 64 (2008) 8355–8361
lysine. The crude Na-AmHex-lysine was used in the following re-
hand, for the system of 1:3 inclusion complex between Na-CiHex-
N3-Ci-lysine and
-CD, the association constants (K21 and K22) were
estimated by Eq. 2. Where S is a substrate, L is an -CD ligand, St is
a total molar concentration of the substrate, Lt is a total molar
concentration of the -CD ligand, and K is a stability constant.
action without further purification. 1H NMR (D2O, 500 MHz):
d
4.09
a
(d, J¼8.2 Hz, 1H, –OCNH–CH–COOH), 2.91 (m, 4H, –CH2–NH2 (Na,
a
N3)), 2.23 (t, J¼7.3 Hz, 2H, –NHCO–CH2–),1.75–1.33 (m,12H, –CH2–).
a
4.3.2.4. Na-Cinnamamidehexancarbonyl-N3-cinnamamide-lysine(Na-
CiHex-N3-CiNH-lysine). trans-Cinnamoyl chloride (1.8 g,11 mmol) in
THF (10 mL) was added to 1.0 N NaOH aqueous solution (20 mL) of
Na-AmHex-lysine. The solution was stirred at 0 ꢂC for 2 h. After the
solution was adjusted at pH¼3 with 1.0 M hydrochloric acid, the
precipitate was collected and washed with ethyl acetate to give Na-
CiHex-N3-CiNH-lysine in 78% yield (1.1 g). 1H NMR (DMSO-d6,
S þ L/SL St ¼ S0 þ K1S0Lt=ð1 þ K1S0Þ; slope ¼ ðSt ꢀ S0Þ=Lt
(1)
S þ LL/L0L ðSt ꢀ S0Þ=½Lꢃ ¼ K10 S0 þ K10 K20 S0½Lꢃ
500 MHz):
d
8.08 (m, 2H, Ph–CH]CH–CONH (Na, N3)), 7.88 (d,
À
Á
S þ L0L/L0L0 Lt ¼ ½Lꢃ 1 þ K10 S0 þ 2K10 K20 S0½Lꢃ
(2)
J¼7.7 Hz,1H, –NHCO–), 7.54 (d, J¼6.7 Hz, 3-H, H of Ph (Na, N3)), 7.42–
7.34 (m, 2-H, H of Ph (Na, N3), 4-H, H of Ph (Na, N3), and 2H, Ph-CH (Na,
N3)), 6.64–6.58 (d, J¼15.8 Hz, 2H, CH–CONH– (Na, N3)), 4.06 (m, 1H,
–CONH–CH–COOH), 3.14 (m, 4H, Ph–CH]CH–CONH–CH2 (Na, N3)),
2.11 (m, 2H, –CONH–CH2),1.66–1.28 (m,12H, –CH2–). Anal. Calcd for
PFGSE NMR diffusion measurements were carried out by using
the bipolar pulse pair stimulated echo (BPPSTE).19 The pulsed gra-
dients’ strength was increased from 6.36ꢁ10ꢀ1 to 43.1 gauss cmꢀ1
.
The time separation of pulsed field gradients and their duration
were 0.10 and 1.0ꢁ10ꢀ3 s, respectively. The sample was not spun
and the airflow was disconnected. The shape of the gradient pulse
was rectangular and its strength varied automatically during the
course of the experiments. The D values, where D represents dif-
fusion coefficient, were determined from the slope of the re-
gression line ln(I/Io) versus G2, according to Eq. 3 in which I/I0 is
observed spin-echo intensity/intensity without gradients, G is
C
30H37N3O5$1H2O: C, 67.24; H, 7.30; N, 7.84. Found: C, 67.00; H, 7.03;
N, 7.75. MALDI-TOF mass m/z¼542 [MþNa]þ.
4.3.2.5. Mono-3-deoxy-3-[Na-cinnamamidehexancarbonyl-N3-cinna-
mamide-lysinamide]-
a-CD
(3). Na-CiHex-N3-Ci-lysine
(0.53 g,
1.0 mmol), DCC (0.28 g, 1.3 mmol), and 1-HOBt (0.18 g, 1.3 mmol)
were dissolved in distilled DMF (20 mL) under ice cooling. The
reacting solution was stirred for 2 h. 3-NH2-a-CD (1.0 g, 1.0 mmol)
in distilled DMF (10 mL) was added to the solution dropwise. The
resulting mixture was stirred at room temperature for 5 days. After
removal of insoluble materials by filtration, the filtrate was poured
into acetone (500 mL). The precipitate was collected and washed
with acetone. The crude product was purified by preparative re-
versed phase chromatography to give 3 in 46% yield (0.7 g). 1H NMR
gradient strength,
D
is delay between the midpoints of the gradi-
is 90–180ꢂ pulse distance. The
ents, is gradient length, and
d
s
calibration of gradients was carried out by a diffusion measurement
of H2O ðD
¼ 2:30 ꢁ 10ꢀ9 m2 sꢀ1
Þ
20 at 25 ꢂC.
H2O
lnðI=I0Þ ¼ ꢀ
g
2G2
d
2ð
D
ꢀ
d
=3 ꢀ
s
=2ÞD
(3)
(DMSO-d6, 500 MHz):
d
8.04 (m, 2H, Ph–CH]CH–CONH (Na, N3)),
-CD),
7.89 (d, J¼8.9 Hz,1H, –NHCO–), 7.78 (d, J¼8.4 Hz,1H, –NHCO–
a
7.54–7.53 (m, 3-H, H of Ph (Na, N3)), 7.41–7.33 (m, 2-H, H of Ph (Na,
N3), 4-H, H of Ph (Na, N3), and 2H, Ph–CH](Na, N3)), 6.64–6.59 (d,
J¼15.8 Hz, 2H, ]CH–CONH (Na, N3)), 5.89–5.21 (m, 11H, O(2)H and
Acknowledgements
The authors thank Dr. Akihito Hashidzume and Mr. Seiji Adachi
(Osaka University) for helpful advise and 2D NMR experiments. The
authors also thank JASCO INTERNATIONAL for support of ESI MS
measurements. This work has been partially supported by Grant-
in-Aid No. A19205014 for Scientific Research and has been con-
ducted with financial support from the ‘Stress and Symbiosis on
Supramolecules’ program of the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
O(3)H of
O(6)H and C(60)H of
3.30 (m, overlaps with HOD), 3.14 (m, 4H, Ph–CH]CH–CONH–CH2
(Na, N3)), 2.13 (m, 2H, CONH–CH2), 1.66–1.25 (m, 12H, –CH2–). 13
NMR (DMSO-d6,100 MHz):
175.5 (Na–C]O–NH–),172.6,172.1 (Na,
a-CD), 5.02–4.78 (m, 6H, C(1)H of a-CD), 4.51–4.40 (m, 8H,
a
-CD), 4.28 (m, 1H, CONH–CH–CONH), 4.15–
C
d
N3–CH2–NH–C]O), 165.5 (–C]O–NH– -CD), 139.2 (N3–Ph–CH]),
a
139.1 (Na–Ph–CH]), 135.7, 135.7, 130.1, 129.6, 128.2, 128.2 (C of Ph),
123.1 (N3–Ph–CH]CH–), 123.1 (Na–Ph–CH]CH–), 103.3, 103.0,
102.8,102.2,101.8 (C(10) and C(1) of
(C(40) and C(4) of
C(5) of
-CD), 60.7, 60.9, 90.9 (C(60) and C(6) of
a
-CD), 83.8, 82.6, 81.7, 81.3, 80.6
-CD), 74.5–71.1 (C(30), C(3), C(20), C(2), C(50), and
-CD), 63.0, 39.5,
Supplementary data
a
a
a
Supplementary data associated with this article can be found in
39.3, 36.0, 29.8, 27.1, 25.9, 23.7 (–CH2–). Positive-ion MALDI-TOF
mass m/z¼1495 [MþNa]þ. Anal. Calcd for C66H96N4O33$5H2O: C,
50.64; H, 6.84; N, 3.58. Found: C, 50.57; H, 6.72; N, 3.66.
References and notes
4.4. Measurements
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trations of
weighed into each of several 1.5 mL microtubes. To each microtube
was added 1.0 mL of aqueous solutions of -CD at various con-
a-CD solutions. Equal amounts of guest compound were
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M. E.; Suwanmala, P.; Rowan, S. J. J. Am. Chem. Soc. 2005, 127, 18202–18211; (f)
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a
centrations. After sonication, microtubes were rotated for a day and
were allowed to stand for 30 min at room temperature. The het-
erogeneous solutions were centrifuged and the solubility of guest
compound was measured by the absorbance of the supernatant. For
the system of 1:1 inclusion complex between CiHexOH and
the association constant (K1) was estimated by Eq. 1. On the other
a-CD,