B. Kuberski, M. Pecul, A. Szumna
FULL PAPER
prior to use. All reported NMR spectra were collected with a
Bruker spectrometer at 500 (1H) and 125 (13C) MHz. Chemical
shifts are reported as δ values relative to the TMS signal defined
at δ = 0.00 ppm (1H) or relative to the CDCl3 signal defined at δ
= 77.00 ppm (13C). Mass spectra were obtained with a Mariner
PerSeptive Biosystem instrument by using the ESI technique. Col-
umn chromatography was performed on silica gel (Kieselgel 60,
200–400 mesh).
22.63, 23.55, 25.00, 26.03, 26.39, 27.40, 28.17, 31.70, 38.44, 42.79,
61.65, 82.90, 85.13, 112.30, 124.06, 124.95, 125.08, 149.78, 151.35,
158.13, 171.89 ppm. MS (ESI): m/z = 1736.2 [C96H152N8O20
–
H]–; isotope profile agrees. C96H152N8O20·2MeOH (1802.36): calcd.
C 65.30, H 8.95, N 6.21; found C 65.34, H 8.96, N 6.00.
5b: To a solution of amine 4a (267 mg, 0.2 mmol) in THF (2 mL)
was added tert-butyl isocyanate (242 µL, 2 mmol). The reaction
mixture was stirred overnight and evaporated to dryness. The crude
product was purified by column chromatography (CH2Cl2/MeOH,
4a: Resorcinarene 2 (712 mg, 1 mmol) and -leucine methylamide
(720 mg, 5 mmol) were dissolved in CH2Cl2 (5 mL). Aqueous
HCHO was then added (37%, 300 µL, 4.0 mmol). The reaction
mixture was vigorously stirred overnight at room temperature. The
reaction mixture was evaporated to dryness, and the crude product
was purified by column chromatography (CH2Cl2/MeOH, 97:3 to
95:5). Subsequent crystallization from CH2Cl2 gave 4a as a white
crystalline material (856 mg, 64%). [α]D = –4.0 (c = 1.0, MeOH).
1H NMR (400 MHz, DMSO, TMS, 303 K): δ = 0.83 (d, J = 6.6 Hz
12 H), 0.85 (d, J = 6.5 Hz 12 H), 0.89 (d, J = 6.8 Hz 12 H), 0.91
(d, J = 6.9 Hz 12 H), 1.36 (m, 12 H), 1.55 (m, 4 H), 1.98 (m, 4 H),
2.13 (m, 4 H), 2.60 (d, J = 4.6 Hz, 12 H, Hl), 3.09 (t, J = 7.1 Hz,
4 H, Hg), 3.54 (d, J = 15.0 Hz, 4 H, Hf), 3.87 (d, J = 15.0 Hz, 4
H, Hf), 4.25 (t, J = 7.6 Hz, 4 H, Hd), 7.19 (s, 4 H, He), 8.02 (br. q,
J = 4.8 Hz, 4 H, Hk) ppm. 13C NMR (100 MHz, DMSO, 303 K):
δ = 22.26, 22.65, 22.78, 22.96, 24.21, 25.40, 25.80, 30.76, 41.47,
41.65, 43.69, 58.53, 108.02, 122.37, 123.37, 123.60, 151.23, 151.72,
172.31 ppm. MS (ESI): m/z = 1335.9 [C88H112N8O12 – H]–; isotope
profile agrees. C76H120N8O12·0.9CH2Cl2 (1414.25, solvent visible
also in NMR): calcd. C 65.31, H 8.68, N 7.92; found C 65.30, H
8.85, N 8.02.
99:1) to give 5b as an off-white powder (180 mg, 52%). [α]2D5
=
+81.5 (c = 0.99, CHCl3). 1H NMR (500 MHz, [D2]TCE, 303 K)
main conformer: δ = 0.40 (br. s, 12 H, Hj), 0.73 (br. s, 12 H, Hj),
0.93 (br. s, 12 H, Ha), 0.99 (d, J = 5.5 Hz, 12 H, Ha), 1.07 (br. m,
4 H, Hi), 1.40 (s, 40 H, Hm, Hh), 1.47 (m, 4 H, Hb), 1.71 (s, 4 H,
Hh), 1.76 (br. m, 4 H, Hc), 2.25 (br. m, 4 H, Hc), 2.94 (br. s, 12 H,
Hl), 3.74 (br. s, 4 H, Hg), 4.31 (br. d, Hf2), 4.44 (br. d, 4 H, Hf1),
4.53 (br. t, 4 H, Hd), 6.37 (br. t, 4 H, Hk), 7.18 (s, 4 H, He), 7.86
(br. s, 4 H, Hn), 8.60 (br. s, 4 H, OH2), 12.13 (br. s, 4 H, OH1)
ppm. 13C NMR (125 MHz, [D2]TCE, 303 K): δ = 25.40, 26.13,
26.60, 26.95, 27.26, 28.14, 29.82, 30.71, 33.31, 33.58, 35.43, 42.06,
46.45, 46.76, 54.53, 63.0 (broad), 115.31, 127.65, 128.18, 128.81,
154.26, 154.80, 163.45, 177.12 ppm. MS (ESI): m/z = 1732.1
[C96H156N12O16 – H]–; isotope profile agrees. C96H156N12O16
(1734.34): calcd. C 66.48, H 9.07, N 9.69; found C 66.24, H 9.03,
N 9.53.
5c: According to the procedure described for 5a. Yield 281 mg,
75%. [α]2D5 = –124.1 (c = 1.00, CHCl3). H NMR (500 MHz, [D2]-
1
TCE, 303 K): δ = 0.94 (br. d, 24 H, Ha), 1.35 (m, 4 H, Hb), 1.50
(s, 36 H, Hm), 2.01 (br. s, 8 H, Hc), 2.58 (br. s, 12 H, Hl), 3.21 (m,
4 H, Hh1), 3.39 (m, 4 H, Hh2), 3.46 (br. s, 4 H, Hf2), 4.05 (d, J =
14.0 Hz, 4 H, Hf1), 4.45 (br. t, 4 H, Hd), 4.59 (m, 4 H, Hg), 5.29
(br. s, 4 H, Hk), 7.08 (s, 4 H, He), 7.18 (br. m, 20 H, Hi-ar), 8.22 (s,
4 H, OH2), 10.53 (s, 4 H, OH1) ppm. 13C NMR (125 MHz, CDCl3,
303 K): δ = 22.50, 22.63, 26.07, 26.37, 28.29, 31.56, 35.07, 42.79,
45.50, 65.07, 83.11, 112.35, 123.83, 124.86, 125.08, 126.41, 128.55,
129.22, 138.46, 149.47, 151.11, 157.89, 171.13 ppm. 15N NMR
(50.7 MHz, CDCl3): δ = –289.1 (NH) ppm. MS (ESI): m/z = 1896.2
[C108H144N8O20 + Na]+, 1872.3 [C108H144N8O20 – H]–; isotope pro-
file agrees. C108H144N8O20 (1874.34): calcd. C 69.21, H 7.74, N
5.98; found C 68.90, H 7.69, N 6.13.
4b: To a solution of resorcinarene 2 (712 mg, 1 mmol) and -phen-
ylalanine methylamide (890 mg, 5 mmol) in CH2Cl2 (5 mL) was
added aqueous HCHO (37%, 300 µL, 4.0 mmol). The reaction
mixture was vigorously stirred overnight at room temperature. The
resulting precipitate was filtered, washed with CH2Cl2 and water,
and then vacuum dried to give analytically pure 4b as a pinkish
1
powder (1.120 g, 76%). [α]D = +2.5 (c = 1.16, MeOH). H NMR
(400 MHz, DMSO, TMS, 303 K): δ = 0.89 (m, 24 H, Ha), 1.31 (m,
4 H, Hb), 1.95 (m, 4 H, Hc), 2.03 (m, 4 H, Hc), 2.55 (d, J = 4.6 Hz,
12 H, Hl), 2.70 (dd, J = 13.4 Hz, J = 8.1 Hz, 4 H, Hh1), 2.83 (dd,
J = 13.4 Hz, J = 5.7 Hz, 4 H, Hh2), 3.28 (t, J = 6.9 Hz, 4 H, Hg),
3.52 (d, J = 14.7 Hz, 4 H, Hf2), 3.88 (d, J = 14.7 Hz, 4 H, Hf1),
4.09 (t, J = 7.6 Hz, 4 H, Hd), 7.12–7.28 (m, 24 H, He, Hi), 7.95 (br.
q, J = 4.7 Hz, 4 H, Hk) ppm. 13C NMR (100 MHz, DMSO, 303 K):
δ = 22.72, 22.85, 25.34, 25.79, 30.61, 41.52, 43.48, 54.52, 61.86,
108.45, 122.37, 123.33, 123.50, 126.22, 128.12, 129.14, 137.58,
5d: According to the procedure described for 5b. Yield 221 mg,
59%. [α]2D5 = –42.5 (c = 1.00, CHCl3). 1H and 13C NMR spectra
were too broad for interpretation. MS (ESI): m/z = 1869.1
[C108H148N12O16 – H]–, 1893.2 [C108H148N12O16 + Na]+; isotope
profile agrees. C108H148N12O16·2H2O (1906.43): calcd. C 68.04, H
8.04, N 8.81; found C 68.08, H 8.03, N 9.05.
150.99, 171.91 ppm. MS (ESI): m/z = 1472.6 [C88H112N8O12
–
H]–; isotope profile agrees. C88H112N8O12·0.8CH2Cl2 (1541.8, sol-
vent visible also in NMR): calcd. C 69.17, H 7.42, N 7.27; found
C 69.10, H 7.38, N 7.15.
5e: To a solution of amine 4a (267 mg, 0.2 mmol) in THF (2 mL)
was added trimethylsilyl isocyanate (280 µL, 2 mmol). The reaction
was stirred for 3 d and then evaporated to dryness and suspended
in acetone (2 mL). The mixture was heated at reflux for 5 min and
then left for 2 h to precipitate. The analytically pure 5e (as a pinkish
powder) was obtained by filtration (217 mg, 66%). An alternative
procedure involves solvent change from THF to methanol. It al-
5a: To a solution of amine 4a (267 mg, 0.2 mmol) in dioxane/water
(2:1, 3 mL) was added Boc2O (348 mg, 1.6 mmol). The reaction
mixture was stirred overnight and evaporated to dryness. The crude
product was purified by column chromatography (CH2Cl2/MeOH,
99:1) to give 5a as an off-white powder (220 mg, 63%). [α]2D5
=
lows shortening of the reaction time to 1 d (216 mg, 66%). [α]2D5
=
–111.3 (c = 1.20, CHCl3). 1H NMR (500 MHz, CDCl3, TMS,
303 K): δ = 0.93 (m, 24 H, Hj), 0.96 (d, J = 2.2 Hz, 12 H, Ha), 0.98
–86.8 (c = 1.00, CHCl3). 1H NMR (500 MHz, CDCl3, TMS,
303 K): δ = 0.91 (d, J = 6.6 Hz, 12 H, Ha), 0.96 (d, J = 6.4 Hz, 12
(d, J = 2.2 Hz, 12 H, Ha), 1.42 (br. s, 40 H, Hb, Hm), 1.56 (m, 4 H, H, Ha), 1.44 (br. m, 4 H, Hb), 1.85 (br. m, 4 H, Hc1), 2.17 (br. m,
Hi), 1.82–1.98 (m, 8 H, Hh), 2.09 (m, 8 H, Hc), 2.53 (br. s, 12 H, 4 H, Hc2), 2.70 (br. d, J = 4.5 Hz, 12 H, Hl), 3.14 (dd, J = 5.7 Hz,
Hl), 4.26 (d, J = 14.8 Hz, 4 H, Hf2), 4.31 (m, 4 H, Hg), 4.56 (t, J J = 13.8 Hz, 4 H, Hh1), 3.41 (dd, J = 13.0 Hz, J = 10.5 Hz, 4 H,
= 7.5 Hz, 4 H, Hd), 4.57 (d, J = 14.8 Hz, 4 H, Hf1), 5.34 (br. s, 4
H, Hk), 7.21 (s, 4 H, He), 8.55 (br. s, 4 H, OH2), 10.77 (br. s, 4 H,
OH1) ppm. 13C NMR (125 MHz, CDCl3, 303 K): δ = 22.16, 22.57,
Hh2), 3.47 (d, J = 15.5 Hz, 4 H, Hf2), 4.24 (d, J = 15.2 Hz, 4 H,
Hf1), 4.47 (br. t, J = 7.8 Hz, 4 H, Hd), 4.52 (m, 4 H, Hg), 6.00 (br.
s, 8 H, Hn), 7.06 (s, 4 H, He), 7.26–7.37 (m, 20 H, Hi), 7.47 (br. q,
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Eur. J. Org. Chem. 2008, 3069–3078